Serum Uric acid level as an estimated parameter predicts all-cause mortality in patients with hemodialysis

Serum Uric acid level as an estimated parameter predicts all-cause mortality in patients with hemodialysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Serum Uric acid level as an estimated parameter predicts all-cause mortality in patients with hemodialysis Sheng-Wen Niu, I-Ching Kuo, Yen-Yi Zhen, Eddy Essen Chang, Cheng-Chung Ting, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4752853/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Serum uric acid (UA) level in end stage renal disease (ESRD) patients is an important physiological index for nutrition and inflammation. Serum UA displays a U-shape associated with all-cause mortality in ESRD patients. In this study, we evaluated relevance of serum UA level with survival rate in ESRD patients according to Charlson comorbidity index (CCI). Methods: Our cohort of2615 subjects suffer from ESRD with CCI < 4 and ≥ 4. Of the 2615 subjects, 1107 subjects are CCI < 4 and others are CCI ≥ 4. The two independent groups were individually marked by serum UA sextiles. Results: With Cox regression, serum UA levels higher than 8.6 mg/dl in the ESRD with CCI < 4 denoted as risk factor for all-cause mortality (hazard ratio (HR): 1.61, 95% CI: 1.01–2.38), compared to these subjects with UA of 7.1-7.7 mg/dl. In contrast, serum UA levels 8.6 mg/dl. Conclusion: Higher serum UA in ESRD subjects with high comorbidities is hardly a risk factor. Profoundly, low UA should be prevented in all ESRD patients. Health sciences/Nephrology/Renal replacement therapy Health sciences/Risk factors Figures Figure 1 Introduction Protein-energy wasting (PEW) as a pathological entity, that is characterized by low protein intake and energetic deposits, in brief, contributing to high mortality in the patients who suffer from chronic kidney disease (CKD) and undergo HD [ 1 ]. Actually, the malnutrition or low serum albumin is a risk factor for all-cause mortality in patients with CKD [ 2 ] or ESRD patients [ 3 ], which is frequently associated with systemic inflammation. Additionally, high uremic toxin levels in serum are not only a pathological index but also develop a uremic milieu in the CKD patients. Subsequently, the uremic milieu elicits oxidative stress and systemic inflammation both promote vascular aging via endothelial dysfunction and vascular calcification[ 4 ]. Intriguingly, cardiovascular disease and cardiovascular mortality arise in the ESRD patients [ 5 ]. As PEW arises, higher inflammation and nutritional parameters, such as cholesterol, sugar and UA, in ESRD patients are the pathological causes of mortality [ 6 ]. The statistical relationship of HbA1c levels in serum and all-cause mortality displays a U-shaped curve in HD patients with highest at HbA1c 9%[ 7 ]. Otherwise, relevance of HbA1c and all-cause mortality in HD patients statistically patterns in a J-shaped curve, especially identified in cardiovascular mortality[ 8 ]. Hsuan Chiu et al. also reported a U-shaped association between non high density lipoprotein cholesterol (LDL) with all-cause and cardiovascular mortality in the patients with CKD stage 3–5[ 9 ]. As mentioned above, serum UA levels is the parameter reflected in both inflammation and nutritional state[ 10 ] and anti-oxidant response [ 11 ] at the same time. It had been documented in literatures that a J-shaped relationship between serum UA levels and all-cause mortality in dialytic patients[ 12 , 13 ]. Additionally, hyperuricemia represents a marker reporting endothelial injury, which may imply AMP-Activated Protein Kinase-mediated inflammation is the pathological cause linked to atherosclerosis [ 14 ]. Meanwhile, Walead Latif, et al reported that hyperuricemia or gouty attack in dialysis patients could also be a reflection of the underlying inflammatory state with subsequent increased risk for all-cause and cardiovascular mortality[ 15 ]. The UA, however, is a nutritional factor, and hypouricemia both concerned with malnutrition-inflammation-atherosclerosis (MIA) syndrome[ 10 ]. Contrary to the general population, low serum UA is associated with higher all-cause mortality in dialysis patients, especially in those with PEW [ 16 ]. In the patients with hyperuricemia, they possess higher antioxidant capacity, thereafter less oxidative damage, and better nutritional status are coincident in them [ 6 ]. Former study has evidenced that hyperuricemia can merely predict renal outcome in CKD patients without metabolic syndrome (MS) nor diabetes (DM)[ 17 ]. Also, mounting evidences have noted that urate lowering therapy is likely improve incidence of stroke without comorbidities [ 18 ]. Mentioned above, UA elevated in serum signifies elevation of inflammation in patients with less comorbidities and exacerbates overall mortality; but in patients with more comorbidities, the similar repertoire may differently display recovery or nutritional condition and relate to less overall mortality. Several studies have been investigated the relationship between comorbidity and mortality in CKD patients during dialysis, and they widely used Charlson score index (CCI) to predict mortality [ 19 ]. Based on the criteria, the subjects which we collected for this study were mainly categorized to less comorbidities and more comorbidities according to CCI, and we proposed to investigate the relationship between serum UA levels and total mortality in the two individual groups. Thus, we questioned of whether the hyperuricemia is or not a risk factor associated with worse survival in dialysis patients and could comorbidities, surveyed with CCI, modify the effect of hyperuricemia. Methods Participants and design The Kaohsiung Hemodialysis Study is a prospective cohort study that examines the quality of patient care based on the HD, surgery, planning, and execution management system developed by the Taiwan Nephrology Society. Between January 1st 1997 and December 31st 2009, HD occurred continuously in three affiliated hospitals of nine related HD clinics at Kaohsiung Medical University in southern Taiwan, with stable HD three times a week for more than 90 days, in patients over 18 years of age. These subjects were collected and followed through May 31st 2013. Among them, 94 subjects stopped follow-up within 6 months, and 39 subjects had more than 10% missing data. In this study, the final cohort was 2615 HD incident subjects. According to CCI, subjects were categorized according to the following criteria: CCI < 3 (n = 1107) and CCI ≥ 4 (n = 1508) (Fig. 1). This study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-G(II)-20160024). We confirmed that informed consent was obtained from all subjects and/or their legal guardians. Dialysis initiation was performed according to the regulations of National Health Insurance (NHI) Administration of Taiwan, which stipulated the required laboratory data, nutritional status, uremic status, and estimated glomerular filtration rate (eGFR). The mean eGFR at the start of dialysis was 4.9 mL/min/1.73 m2, and the mean residual urine was 560 ml. A total of 178 subjects (6.1%) received peritoneal dialysis during the same period. The NHI administration provides full coverage of HD therapy and erythropoiesis stimulating agent therapy at a fixed fee. Attending physicians are rotated between dialysis centers and dialysis machines are involved; artificial kidneys and water management have similar applications. Furthermore, we do not reduce the surface area of ​​the dialyzer if the KDIGO recommended target URR (70%) or Kt/V (> 1.4) is achieved. But if the minimum requirements of URR (> 65%) or Kt/V (> 1.2) in the Taiwan Nephrology Society guidelines are not met, we will increase the surface area of ​​the dialyzer. Measurements Baseline variables included demographic characteristics (age, sex, and year of enrollment), history of DM, congestive heart failure (CHF), hypertension, stroke, cancer, and hepatitis. We obtained and averaged test results (pre- and post-dialysis body weight (BW)), laboratory data (serum creatinine, post-dialysis blood urea nitrogen (BUN), albumin (methyl bromide) with the Roche cobas® 6000 analyzer Phenol green (BCG) albumin determination), white blood cell count (WBC), heme, total cholesterol, cardiothoracic ratio (CTR), iron saturation and glucose (AC)) and HD parameters (UF/BW ratio, vascular access, Kt/V(Daugirdas), URR and normalized protein catabolic rate (nPCR) between 4th and 9th month). Subjects with DM and hypertension were identified through clinical diagnosis. Laboratory data were recorded monthly, and statistical analysis was performed on average data 6 months after stable dialysis. Assessing dialysis adequacy using the single-cell Daugirdas formula Kt/V = − 1n((postBUN/preBUN) − 0.008 × t) + [(4 − 3.5 × (postBUN/preBUN)) × UF/BW] and URR is the ratio of (preBUN − postBUN) as numerator to the denotator preBUN (BUN: mg/dL). Post-dialysis BUN values ​​are described according to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines as follows [ 20 ]: (1) the ultrafiltration rate is reset to zero, (2) the blood pump is slowed to 100 mL/min for 10 − 20 seconds, ( 3) Then stop the pump and (4) withdraw a sample from the arterial blood line sampling port or from the tubing connected to the arterial needle[ 21 ],[ 22 ]. Outcomes Based on the CCI criteria, all subjects were categorized by CCI < 3 (n = 1107) and CCI ≥ 4 (n = 1508) (Fig. 1). Subjects were followed from month 4 of HD or death to the end of month 20. All-cause mortality was confirmed by review of death certificates using charts or the National Death Index. Statistical analysis Baseline PA characteristics were assessed as percentages of categorical profiles, mean ± standard deviation (SD) for continuous variables with approximately normal distribution, and median and six-quartile range for continuous variables with skewed distribution. A Markov chain Monte Carlo method was applied to minimize the effect of missing covariates (seven covariates had less than 5% missing values). Multiple linear regression was used to evaluate the relationship between URR, Kt/V and the significance factors described in Table 1 . The analysis was initially performed without adjustments but were subsequently applied to several sets of covariates stratified in this study. These models also resolved covariates with P < 0.05 in univariate analysis and log-transformed continuous variables with skewed distributions to obtain normal distributions. Age at dialysis initiation, sex, year of entry, DM, hypertension, hepatitis, CHF, post-dialysis BW, nPCR, UF:BW ratio, creatinine, hemoglobin, WBC, albumin, AC, log-transformed cholesterol and phosphorus were recorded in this study. Also tested based on sex, age (≥ 65 years), DM, CHF, hepatitis, hypertension, anemia (heme < 10 g/dL), albumin (< 3.5 g/dL), UF (mean), and BW (mean value). Interactions between subgroups were examined. A P value < 0.05 is the threshold for statistical significance. Statistical analyzes were performed using R 4.1.3 software (R Foundation for Statistical Computing, Vienna, Austria) and SPSS version 20.0 (SPSS Inc., Chicago, IL). Table 1 Demographic data of incident hemodialysis patients in the cohort. UA Variables All 8.6 p value No. of patients 2615 428 (16.4%) 448 (17.1%) 446 (17.1%) 436 (16.7%) 425 (16.3%) 432 (16.5%) - Demographics Age (years) 59.1 (14.2) 64.9 (14.1) 61.7 (14.0) 59.4 (13.9) 57.7 (13.9) 56.5 (13.5) 54.0 (13.1) < 0.001 Gender, (female %) 1317 (50.4%) 247 (57.7%) 267 (59.6%) 220 (49.3%) 197 (45.2%) 191 (44.9%) 195 (45.1%) < 0.001 Hepatitis 361 (13.8%) 58 (13.6%) 58 (12.9%) 70 (15.7%) 63 (14.4%) 58 (13.6%) 54 (12.5%) 0.753 Congestive heart failure 850 (32.5%) 121 (28.3%) 158 (35.3%) 151 (33.9%) 115 (26.4%) 149 (35.1%) 156 (36.1%) 0.107 Ischemic heart disease 439 (16.8%) 61 (14.3%) 63 (14.1%) 86 (19.3%) 67 (15.4%) 86 (20.2%) 76 (17.6%) 0.038 Stroke 194 (7.4%) 32 (7.5%) 37 (8.3%) 40 (9.0%) 28 (6.4%) 30 (7.1%) 27 (6.3%) 0.239 Cancer 161 (6.2%) 25 (5.8%) 34 (7.6%) 32 (7.2%) 25 (5.7%) 23 (5.4%) 22 (5.1%) 0.219 Diabetes mellitus 1261 (48.2%) 206 (48.1%) 232 (51.8%) 238 (53.4%) 207 (47.5%) 206 (48.5%) 172 (39.8%) 0.004 Hypertension 1831 (70.0%) 261 (61.0%) 315 (70.3%) 327 (73.3%) 305 (70.0%) 314 (73.9%) 309 (71.5%) 0.001 Charlson comorbidity index 3.9 (1.7) 3.9 (1.7) 4.0 (1.8) 4.1 (1.8) 3.8 (1.6) 4.0 (1.7) 3.7 (1.5) < 0.001 Laboratory data WBC (x1000/ul) 7.0 (2.3) 7.1 (2.5) 7.0 (2.4) 7.0 (2.3) 7.0 (2.1) 6.9 (2.1) 7.0 (2.3) 0.871 Hb (g/dl) 9.9 (1.2) 9.6 (1.1) 9.9 (1.2) 10.0 (1.2) 10.1 (1.2) 10.0 (1.3) 9.6 (1.2) < 0.001 Albumin (g/dl) 3.7 (0.4) 3.5 (0.5) 3.7 (0.4) 3.8 (0.4) 3.8 (0.4) 3.8 (0.3) 3.8 (0.4) < 0.001 Cholesterol (mg/dl) 187.0 (45.1) 174.7 (44.1) 183.0 (42.3) 184.4 (45.5) 190.1 (44.2) 192.1 (43.7) 198.1 (47.2) < 0.001 Glucose[AC] (mg/dl) 136.4 (60.8) 139.7 (64.8) 137.6 (59.2) 138.4 (60.0) 134.3 (57.5) 136.0 (59.0) 132.5 (63.9) 0514 Creatinine (mg/dl) 9.2 (2.8) 7.2 (2.4) 8.2 (2.4) 9.2 (2.5) 9.7 (2.5) 10.1 (2.7) 11.2 (2.7) < 0.001 K (mEq/l) 4.7 (0.7) 4.5 (0.7) 4.5 (0.7) 4.6 (0.7) 4.7 (0.6) 4.8 (0.6) 4.8 (0.7) < 0.001 Ca (mg/dl) 9.3 (0.8) 9.3 (0.9) 9.3 (0.7) 9.3 (0.7) 9.3 (0.8) 9.3 (0.8) 9.4 (0.9) 0.486 P (mg/dl) 5.0 (1.2) 4.2 (1.2) 4.7 (1.1) 4.9 (1.1) 5.2 (1.1) 5.2 (1.2) 5.7 (1.2) < 0.001 BW post dialysis (kg) 56.7 (11.7) 51.7 (10.3) 54.2 (10.5) 56.3 (10.4) 57.2 (11.8) 59.6 (11.8) 61.2 (12.6) < 0.001 UF/BW ratio (%) 3.8 (1.5) 3.6 (1.5) 3.7 (1.5) 3.9 (1.6) 3.9 (1.4) 3.9 (1.5) 3.9 (1.5) 0.0030 BUN pre-HD (mg/dl) 70.3 (18.1) 59.2 (17.1) 65.4 (17.0) 68.0 (15.4) 72.2 (15.8) 74.8 (17.0) 82.5 (17.3) < 0.001 URR 0.7 (0.1) 0.7 (0.1) 0.7 (0.1) 0.7 (0.1) 0.7 (0.1) 0.7 (0.1) 0.7 (0.1) < 0.001 Kt/V (Gotch) 1.3 (0.2) 1.3 (0.2) 1.3 (0.2) 1.3 (0.2) 1.3 (0.2) 1.3 (0.2) 1.2 (0.2) < 0.001 nPCR 1.2 (0.3) 1.1 (0.3) 1.1 (0.3) 1.1 (0.3) 1.2 (0.3) 1.2 (0.3) 1.2 (0.3) < 0.001 Cardiac/thoracic ratio (%) 50.3 (6.5) 51.5 (6.7) 50.8 (6.5) 50.2 (6.3) 49.7 (6.6) 49.4 (6.5) 50.2 (6.2) < 0.001 Outcomes All-cause mortality 1115 (42.6%) 247 (57.7%) 198 (44.2%) 198 (44.4%) 162 (37.2%) 165 (38.8%) 145 (33.6%) < 0.001 WBC: white blood cells, Hb: hemoglobin, K: potassium, Ca: calcium, P: phosphate, BW: body weight, UF: ultrafiltration, BUN: blood urea nitrogen, HD: hemodialysis, URR: urea reduction ratio, nPCR: normalized protein catabolic rate. Data are presented as mean (standard error), median (interquartile range), or count (percentage%). * (P < 0.05) indicates a significant difference. Ethics declarations This study was planned to be presented in accordance with the guidelines of the Declaration of Helsinki. In addition, this study was also approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-G(II)-20160024). Results Patients’ characteristics by UA quintiles Table 1 summarizes the baseline clinical and biochemical characteristics of the 2615 participants based on the presence of serum UA levels. The mean ages from the subject cohort were 59.1 ± 14.2 years old. Moreover, among subjects with UA < 5.8 mg/dl was also related to older age, more female, and higher prevalence of DM, lower prevalence of hypertension, higher Charlson comorbidity index (CCI), lower level of albumin, cholesterol, creatinine, potassium, phosphate, BW post dialysis, UF/BW ratio, BUN pre-dialysis and nPCR, higher level of AC-glucose, Kt/V (Gotch) and cardiac/ thoracic ratio, and higher all-cause mortality. Among subjects with UA = 7.1–7.7 mg/dl was also related to the highest level of hemoglobin. . Multivariate linear regression for UA The results of multivariate linear regression for serum UA (Table 2 ) indicated that higher UA level is significantly related to male, lower age at dialysis, shorter entry-year, lower prevalence of DM, higher pre-dialytic BW, lower Kt/V (Gotch), higher nPCR, higher albumin level, higher log of cholesterol level, higher phosphate level and higher log of PTH level. Although some parameters are present in different trends of association with UA quintiles in Table 1 , CCI and serum UA in the subjects are not in statistical relevance as noted in Table 2 . Table 2 Multivariate linear regression (Full adjusted model for UA level) (continuous) Variables β coefficient 95% CI β coefficient p Gender_(female vs male) -0.164 -0.283 to -0.045 0.007 Age at dialysis (year) -0.008 -0.012 to -0.004 < 0.001 Entry year (late vs early) -0.211 -0.324 to -0.099 < 0.001 Hepatitis -0.070 -0.215 to 0.075 0.347 Congestive heart failure 0.032 -0.079 to 0.144 0.568 Cancer 0.092 -0.115 to 0.298 0.385 Diabetes mellitus -0.188 -0.307 to -0.070 0.002 Hypertension 0.051 -0.062 to 0.164 0.377 Post-dialytic body weight (kg) 0.012 0.007 to 0.017 < 0.001 Kt/V (Gotch) -0.524 -0.804 to -0.243 < 0.001 UF/BW ratio100 0.026 -0.009 to 0.061 0.147 nPCR 0.612 0.420 to 0.804 < 0.001 W.B.C. (1000/ul) 0.016 -0.007 to 0.040 0.176 Hemoglobin (g/dl) -0.007 -0.052 to 0.038 0.745 Albumin (g/dl) 0.256 0.102 to 0.409 0.001 Cholesterol log 1.361 0.839 to 1.883 < 0.001 Glucose[AC] (mg/dl) 0.000 -0.001 to 0.001 0.761 P (mg/dl) 0.267 0.220 to 0.314 < 0.001 Total calcium (mg/dl) -0.008 -0.074 to 0.058 0.814 PTH hormone log 0.123 0.044 to 0.202 0.002 UA: uric acid, PTH: parathyroid, other abbreviations are the same as in Table 1 . Data are presented as in Table 1 . Serum UA quintiles, sixtiles and clinical outcomes In serum UA quintiles group, in the fully-adjusted Cox regression (Table S2), subgroup of UA = 6–7 mg/dl is statistically related to 39% increase in risk of all-cause mortality (HR: 1.39, 95% CI: 1.06–1.82) compared with of UA > 9 mg/dl with CCI ≥ 4; and subgroup of UA > 9 mg/dl is significantly related to about double increase in risk of all-cause mortality (HR: 1.99, 95% CI: 1.18–3.36) compared with of UA > 9 mg/dl with CCI < 4. In UA sextiles group, in the fully-adjusted Cox regression (Table 3 ), subgroup of UA 8.6 mg/dl with total; subgroup of UA < 5.8 mg/dl is significantly related to 53% increase (HR: 1.53, 95% CI: 1.20–1.95), UA = 6.5–7.1 mg/dl is significantly related to 37% increase (HR: 1.37, 95% CI: 1.08–1.72), UA = 7.7–8.6 mg/dl is significantly related to 34% increase (HR: 1.34, 95% CI: 1.06–1.69) in risk of all-cause mortality compared with of UA > 8.6 mg/dl with CCI ≥ 4; subgroup of UA > 8.6 mg/dl is significantly related to 61% increase in risk of all-cause mortality (HR: 1.61, 95% CI: 1.01–2.38) compared with of UA = 7.1–7.7 mg/dl with CCI = 4 and Charson < 4 by 2 groups UA Sextile 1 2 3 4 5 6 Variables 8.6 Number 428 448 446 436 425 432 total unadjusted 2.22 (1.83–2.69)** 1.57 (1.29–1.92)** 1.48 (1.21–1.81)** 1.20 (0.98–1.48) 1.25 (1.02–1.54)* 1 (reference) fully-adjusted 1.31 (1.06–1.63)* 1.09 (0.88–1.36) 1.21 (0.98–1.49) 1.07 (0.86–1.32) 1.20 (0.97–1.48) 1 (reference) charlson ≥ 4 unadjusted 2.67 (2.15–3.32)** 1.72 (1.38–2.15)** 1.64 (1.32–2.06)** 1.39 (1.11–1.76)* 1.38 (1.10–1.74)* 1 (reference) fully-adjusted 1.53 (1.20–1.95)** 1.19 (0.93–1.51) 1.37 (1.08–1.72)* 1.22 (0.96–1.55) 1.34 (1.06–1.69)* 1 (reference) charlson < 4 unadjusted 1.88 (1.20–2.94)* 1.54 (0.97–2.45) 1.27 (0.79–2.06) 1 (reference) 0.96 (0.57–1.63) 1.27 (0.79–2.04) fully-adjusted 1.21 (0.75–1.95) 1.51 (0.94–2.43) 1.35 (0.82–2.23) 1 (reference) 1.18 (0.69–2.04) 1.61 (1.01–2.38)* HR: hazard ratio, *:<0.05, **:<0.01, ***:<0.001, other abbreviations are the same as in Table 2 . Data are presented as in Table 2 . Serum UA level could be an indicator reported nutritional status in the dialysis subjects with high CCI the comorbidities related systemic inflammation and energetic exhausting, so lower serum UA level is related to higher mortality; The dialysis subjects with low CCI the comorbidities, serum UA level per se may indirectly reflect inflammation. Therefore, higher serum UA level is related to higher mortality instead. Discussion Hyperuricemia (serum UA levels > 7 mg/dl in men and > 6 mg/dl in women) and gout are both common in CKD because of the progressive loss of eGFR and renal clearance of UA in patients with CKD or ESRD. Reduced serum UA levels compared with subjects without CKD[ 23 ]. In the people without CKD, masculine population has tendency with higher mean serum levels (me/dl) compared to feminine [ 24 ]. In the study of Hung er al.[ 25 ], there was no gender difference in mean serum UA levels (mg/dl) of maintenance HD patients (7.6 ± 1.2 in men ( n = 68) and 7.8 ± 1.6 in women ( n = 78), P = 0.329). But in another study with larger cohort (n = 4242), the prevalence of hyperuricemia was 22.2%, and it was significantly higher in masculine than in feminine (25.2% vs. 17%, p 7 mg/dl in masculin is 54.7% (719/1315), the rate of serum UA level > 6 mg/dl in feminine is 48.2% (991/2057) (Table 1 ), under full adjusted of other variables (Table 2 , n = 2615), the mean level of UA in feminine is 0.164 mg/dl less than in masculine (95%CI=-0.283 to -0.045, p = 0.007). A study from Taiwan NHI Research Database has pointed that CKD subjects with gout will progress ESRD and their HR is 1.41 higher than the CKD subjects without gout, which were statistically analyzed in the CKD subjects with age ranged from 45 to 59 years. HR of CKD subjects with gout progressed ESRD is 1.58 comparted to CKD subjects without gout, which is statistically calculated in subjects aged 60 and above [ 27 ]. In contrast, our study highlights that the higher serum UA level, the lower average age is noted ( p < 0.001, Table 1 ). Under full adjusted, while age is one year elder, serum UA level is 0.008 mg/dl lower (95%CI=-0.012 to -0.004, p < 0.001, Table 2 ). This result infers that nutritional status might be the cause. Excessive BW (OR 0.4 [0.2; 0.9]) and Kt/V urea < 1.2 (OR 0.1 [0.04; 0.2]) significantly decreases the efficacy of HD, ant they both easily caused more prevalence of hyperuricemia[ 28 ]. The present study unveiled that under full adjusted, pre-dialysis BW is 1 kg heavier, UA level is 0.012 mg/dl higher (95%CI = 0.007 to 0.017, p < 0.001); Kt/V is 1.0 lower, UA level is 0.524 mg/dl higher (95%CI= -0.804 to -0.243, p < 0.001). Otherwise, serum UA level, albumin level and nPCR all reflect nutritional status, and higher UA level, albumin level and nPCR are related to lower mortality[ 29 ]. In present study, under full adjusted, nPCR is 1 g/kg/day higher, uric acid is 0.612 mg/dl higher (95%CI = 0.420 to 0.804, p < 0.001); albumin level is 1mg/dl higher, UA level is 0.256 mg/dl higher. Hyperuricemia might be one of major contributors for CKD development or progression. Although none of precise cutoff UA value as an available parameter report risk impact for kidney damage, it seemed that elevation of serum UA escalates risk for all-cause-mortalith [ 30 ]. In a randomized clinical cases comparing with sevelamer and calcium-based phosphate binders, sevelamer drug regimen, in turn, can significantly reduce in serum UA amount in CKD patients [ 31 ]. In another Swedish study, after adjustment for phosphate binders and vitamin D treatment, serum UA levels remained significantly associated with plasma KDa phosphate (ρ = 0.24; P < 0.0001) and Ca × P product values ​​(ρ = 0.19; P = 0.001)[ 32 ]. In a retrospective cohort study of 16,057 HD subjects treated at 564 NephroCare centers in EMEA (Europe, Middle East, and Africa; n = 15,127) and Latin America (n = 930), in terms of laboratory parameters, subjects with higher serum UA levels also had higher values ​​for phosphate, albumin, creatinine, total cholesterol, triglycerides, normalized protein catabolic rate (nPCR), and parathyroid hormone[ 33 ]. Our study has revealed that UA level is positive parameter related to serum phosphate level (Table 1 ). Under full adjusted, serum phosphate level is 1 mg/dl higher, the serum UA level is 0.267 mg/dl higher; the level of natural log to PTH is 1 higher, the UA level is 0.123mg/dl higher; the level of natural log to total cholesterol is 1 higher, the serum UA level is 1.361 mg/dl higher (Table 2 ). The correlation between serum UA level and phosphate may attributed to efficacy of HD and nutritional status, as the same as cholesterol. Hyperuricemia is associated with increased morbidity and mortality. Even so, data collected from HD subjects is not totally consistent with subjects with hyperuricemia [ 34 ]. In ESRD patients, total antioxidant capacity was associated with serum UA levels, primarily because of higher serum UA levels[ 11 ], and lower serum UA levels may result in reduced total antioxidant capacity in subjects undergoing dialysis, although further studies are needed to determine the exact mechanism[ 35 ]. Another study in Taiwan declared that hyperuricemia predicts worse renal outcome only in patients without DM or MS [ 36 ]. One Taiwanese NHI database study revealed therapy with benzbromarone as uricosuric agents decrease the incidence of stroke especially in patients without or with less comorbidities[ 18 ]. The use of uricosuric agents or xanthine oxidase inhibitors to lower uric acid levels as primary or secondary prevention of cardiovascular disease [ 37 ] or renal disease is also the subject of many completed and ongoing clinical trials[ 38 ]. Our study revealed that the higher mortality rate and lower serum UA levels both are correlated overall in ESRD subjects (compared with of UA > 8.6 mg/dl), subgroup of UA 9.0 mg/dl, none of statistic significant difference exists in risk of all-cause mortality in other subgroup of different UA levels as quintiles (table S1 ). In former studies, Hsu et al. reported that ‘low level’ and ‘high level’ groups serum represent higher risk of mortality than those in the ‘average level’ group in 2004 as taking insight into UA levels in ESRD patients [ 12 ]. In 2020, Zawada el al. stated that the relationship of serum UA and all-cause mortality exhibits in U-shaped pattern in a retrospective cohort study of 16,057 HD subjects treated during 2007 to 2016 in NephroCare centers as documented in the European Clinical Database (EuCliD) [ 13 ]. Alternatively, Hu et al. had reported that relationship between serum UA levels and the risk of ischemic stroke displays a J-shaped in another hospital-based cross-sectional study with 2,195 individuals in 2020 [ 39 ]. Additionally, S Kawasoe et al study reported that relationship between serum UA level and hypertension represent the similar ‘J-shaped’ in a cohort of 236,221 subjects (age, 56.0 ± 15.0 years; 107,146 men) in 2021. [ 40 ]. Similarly, relationship of dialysis subjects and lipid and cardiovascular mortality is a J-shaped pattern in reverse epidemiology (lower lipid levels and higher vascular events compared to general population) in 2022 [ 41 ]. Documented literature implies that the higher serum UA level is an elevated risk for ischemic stroke among patients with hypertension [ 42 ]. When the subjects have drug regimen “uricosuric agents” to reduce serum UA level, incidence of stroke would be lower [ 18 ]. Interestingly, the stroke patients would get poor recovery including short-term poor functional outcome, when they have lower serum UA level [ 43 ] and post-stroke depression[ 44 ]. Herein, we bring up a hypothesis: relationship of serum UA and mortality in “high level” and “low level” are distinguished in patients with fewer comorbidities and more comorbidities. Lower serum UA in patients with more comorbidities and higher serum UA in patients with fewer comorbidities both trend toward higher mortality. We noticed different variant, CCI, that leads to higher mortality between higher levels and lower levels of serum UA. In respect to serum UA level and mortality in ESRD patients, we found that high UA level was associated with high mortality with CCI < 4; and contrarily low UA level was associated with high mortality with CCI ≥ 4. In the present study, the higher mortality rate associated with higher serum UA levels with CCI 8.6 mg/dl is significantly related to 61% increase in risk of all-cause mortality (HR: 1.61, 95% CI: 1.01–2.38) compared with of UA = 7.1–7.7 mg/dl as sextiles in Table 3 ; and subgroup of UA > 9.0 mg/dl is significantly related to about double in risk of all-cause mortality (HR: 1.99, 95% CI: 1.18–3.36) compared with of UA = 7.0–8.0 mg/dl as quintiles in table S3). It has been well known that serum UA levels correlate with many cardiovascular diseases [ 45 – 47 ] or renal injury without or with less comorbidities[ 36 ], including older age, male gender and hypertension. In our study, we evidenced significant differences in serum UA levels between masculine and feminine ( P < 0.001), as well as between hypertensive and non-hypertensive patients ( P = 0.0235). There was also significantly negative correlation ( P < 0.001) between patient age and serum UA levels, and it is considered that there are less comorbidities in the younger. The serum UA levels as a risk factor for kidneyinjury [ 48 ] or atherogenic factor as a number of in vitro and in vivo studies reported the UA crystal can cause renal inflammation[ 49 ], oxidative stress[ 50 ], endothelial lesion [ 51 , 52 ], hypertension[ 53 , 54 ], and activate RAAS[ 55 ] to provoke cardiovascular disease or renal disease. Elevating serum UA level promotes oxygenation of LDL and increases lipid peroxidation[ 56 ], and production of oxygen free radicals (ROS) with subsequent endothelial dysfunction[ 57 ]. The hyperuricemia may lead to the progression of atherosclerosis[ 14 ]. High serum UA levels are associated with increased platelet adhesiveness[ 58 ] followed by thrombi formation in HD patients[ 59 ]. Past study also unveiled that hyperuricemia increases cardiovascular risk in patients with hypertension[ 60 ]. Although higher serum UA level was not associated with more risk of ischemic heart disease and stroke (Table 1 ), but associated with more risk of hypertension significantly in this study ( P = 0.0235, Table 1 ). Therefore, it is possible that higher levels of serum UA reflect status of inflammation and may be related to endothelial dysfunction, hypertension and cardiovascular disease in our HD patients with CCI < 4. But the most important, we should not restrict nutrient supply in those with high UA and high comorbidities. On the contrary, the higher mortality rate associated with lower serum UA levels with CCI ≥ 4 (compared with of UA > 8.6 mg/dl, subgroup of UA < 5.8 mg/dl is significantly related to 53% increase in risk of all-cause mortality (HR: 1.53, 95% CI: 1.20–1.95), UA = 6.5–7.1 is significantly related to 37% increase in risk of all-cause mortality (HR: 1.37, 95% CI: 1.08–1.72), and UA = 7.7–8.6 is significantly related to 34% increase in risk of all-cause mortality (HR: 1.34, 95% CI: 1.06–1.69) as sextiles in Table 3 ; compared with of UA > 9.0 mg/dl, subgroup of UA = 6.0–7.0 mg/dl is significantly related to 39% increase in risk of all-cause mortality (HR: 1.39, 95% CI: 1.06–1.82) as quintiles in table S1 ). There are also some additional hypotheses that explain the lower mortality rates associated with the higher serum uric acid levels. A low serum level of UA may have been an indicator of malnutrition in the patients[ 35 ], just like Pre-dialysis BUN[ 61 ], lipid profiles[ 62 ] are both regarded as indicators of nutritional status in dialysis patients, and low UA levels[ 29 ] and pre-dialytic BUN levels[ 63 ] are often surrogates of inadequate protein intake. Protein-energy wasting (PEW), referred to uremic malnutrition, is caused by inadequate nutrient intake, nutrient loss during dialysis, hyper-catabolism associated with dialysis[ 29 ]. Uric acid is an end product of protein metabolism, so PEW leads to low BMI hypocholesterolemia, low level of pre-dialytic BUN and even low level of uric acid[ 64 ]. The nPCR is another well-recognized nutrition parameter. In our study, serum UA levels were significantly correlated with both pre-dialysis BUN ( P < 0.001, Table 1 ) and nPCR ( r = 0.621, P < 0.001, Table 2 ). These findings suggest that serum UA is a alternative marker of protein intake. Lower serum UA levels are associated with lower antioxidant capacity, and elevated UA levels may reduce oxidative damage associated with atherosclerosis and aging in humans[ 65 ]. Kim et al. found that better antioxidant capacity was correlated with higher levels of serum UA in peritoneal dialysis patients[ 66 ]. UA also contributes up to 60% to the free radical removal capacity of blood[ 67 ] and its concentration increases significantly during stroke[ 68 ]. Therefore, in addition to inflammatory factors, UA also has important in vivo [ 69 ] and in vitro [ 57 ] antioxidant properties. High concentrations of circulating urate are considered one of the major antioxidants in plasma, protecting cells from oxidative damage, thereby helping to extend human lifespan and reduce the risk of cancer[ 70 ]. Therefore, it is possible that lower levels of serum uric acid reflect status of malnutrition and result in reduced total antioxidant capacity in our HD patients with CCI ≥ 4. However, we need further studies to clarify above paradoxical issues in HD patients with CCI < 4 and ≥ 4. Limitations This study included HD patients and measured mean dialysis dose between months 4 and 9 of HD. This may have prevented survival bias and ensured stable measurement of dialysis dose. This study has its limitations. First, this is an observational study and cannot establish a causal relationship between SUA, CCI, and clinical outcomes. Second, some other data are lacking, such as residual urine, blood pressure, medications, and body mass index. Third, Kt, BSA, and TEE records are missing, so comparison with Kt/V is not possible. Last, clinical relevance is important because inflammation and malnutrition have pathological impacts and we did not prove inflammation in any way. Conclusions In summary, low UA levels of serum uric acid in our HD patients were associated with worse mortality with CCI ≥ 4; paradoxically, high levels were associated with worse mortality with CCI < 4. High UA was not a risk in those with CCI ≥ 4, but low UA should be prevented in all HD patients. Declarations Author Contributions S.-W.N., C.-C.H., H.Y.-Y.L., I.-C.K., Y.-W.C., J.-M. C. and S.-J. H. made the conceptualization. S.-W.N., C.-C.H., Y.-Y.Z., E.E.C., C.-T.C., J.-M.C. and S.-J.H. wrote the methodology. C.-C.H., and Y.-Y.Z. supplied the software. S.-W. N., H.Y.-Y.L. and C.-T.C. made the validation. H.Y.-Y.L. and Y.-Y.Z. made the formal analysis. S.-W. N., C.-C. H., H.Y.-Y.L., I.-C.K., Y.-Y.Z., E.E.C., Y.-W. C., J.-M. C. and S.-J. H. made the investigation. H.Y.-Y.L. and C.-C.H. supplied the resources. S.-W.N., C.-C.H. and Y.-Y.Z. wrote the original draft preparation. S.-W.N., H.-Y.L., C.-C.H., Y.-Y.Z., E.E.C., C.-T.C., and S.-J.H. wrote the review and editing. E.E.C. H.Y.-Y.L. and C.-C.H. made the visualization. Y.-W.C., J.-M.C. and S.-J.H. made the supervision. H.Y.-Y. L., C.-C.H. and S.-J. H. made the project administration. S.-J. H supplied the funding acquisition. All authors reviewed and agreed to publish the manuscript. Acknowledgement This study was supported by grants from Kaohsiung Municipal Ta-Tung Hospital (KMTTH-110-005, KMTTH-111-017, KMTTH-112-003), Kaohsiung Medical University Research Foundation (KMU-QA109001), NSYSU-KMU JOINT RESEARCH PROJECT (#NSYSUKMU 110-P008), and Ministry of Science and Technology (MOST-107-2314-B-037-071-, MOST 109-2314-B-037-092-, MOST 109-2314-B-037-094-, MOST 110-2314-B-037-068-MY3). Funding: This research received no external funding. Informed Consent Statement: Written informed consent has been obtained from the patient(s) to publish this paper. Data Availability Statement: The datasets used and analysed during the current study available from the corresponding author on reasonable request. Conflicts of Interest: The authors declare no conflict of interest. References de Mutsert, R.; Grootendorst, D.C.; Axelsson, J.; Boeschoten, E.W.; Krediet, R.T.; Dekker, F.W.; Group, N.S. Excess mortality due to interaction between protein-energy wasting, inflammation and cardiovascular disease in chronic dialysis patients. Nephrology Dialysis Transplantation 2008 , 23 , 2957-2964. Song, H.; Wei, C.; Hu, H.; Wan, Q. Association of the serum albumin level with prognosis in chronic kidney disease patients. Int Urol Nephrol 2022 , 54 , 2421-2431, doi:10.1007/s11255-022-03140-5. Hao, N.; Cheng, B.C.; Yang, H.T.; Wu, C.H.; Lei, Y.Y.; Chao, M.C.; Wang, P.Y.; Kuo, L.C.; Moi, S.H.; Yang, C.H.; et al. Time-varying serum albumin levels and all-cause mortality in prevalent peritoneal dialysis patients: a 5-year observational study. BMC Nephrol 2019 , 20 , 254, doi:10.1186/s12882-019-1433-8. Donato, A.J.; Morgan, R.G.; Walker, A.E.; Lesniewski, L.A. Cellular and molecular biology of aging endothelial cells. Journal of molecular and cellular cardiology 2015 , 89 , 122-135. Alves, F.C.; Sun, J.; Qureshi, A.R.; Dai, L.; Snaedal, S.; Barany, P.; Heimbürger, O.; Lindholm, B.; Stenvinkel, P. The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease. PloS one 2018 , 13 , e0190410. Domínguez-Zambrano, E.; Pedraza-Chaverri, J.; López-Santos, A.L.; Medina-Campos, O.N.; Cruz-Rivera, C.; Bueno-Hernández, F.; Espinosa-Cuevas, A. Association between serum uric acid levels, nutritional and antioxidant status in patients on hemodialysis. Nutrients 2020 , 12 , 2600. Al-Ghamdi, S.M.; Bieber, B.; AlRukhaimi, M.; AlSahow, A.; Al Salmi, I.; Al Ali, F.; Al Aradi, A.; Pecoits-Filho, R.; Robinson, B.M.; Pisoni, R.L. Diabetes Prevalence, Treatment, Control, and Outcomes Among Hemodialysis Patients in the Gulf Cooperation Council Countries. Kidney international reports 2022 , 7 , 1093-1102. Raghavan, S.; Vassy, J.L.; Ho, Y.L.; Song, R.J.; Gagnon, D.R.; Cho, K.; Wilson, P.W.; Phillips, L.S. Diabetes mellitus–related all‐cause and cardiovascular mortality in a national cohort of adults. Journal of the American Heart Association 2019 , 8 , e011295. Chiu, H.; Wu, P.-Y.; Huang, J.-C.; Tu, H.-P.; Lin, M.-Y.; Chen, S.-C.; Chang, J.-M. There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3–5. Scientific Reports 2020 , 10 , 12749. Stamp, L.; Dalbeth, N. Urate-lowering therapy for asymptomatic hyperuricaemia: a need for caution. In Proceedings of the Seminars in Arthritis and Rheumatism, 2017; pp. 457-464. Kim, S.B.; Yang, W.S.; Min, W.K.; Lee, S.K.; Park, J.S. Reduced oxidative stress in hypoalbuminemic CAPD patients. Perit Dial Int 2000 , 20 , 290-294. Hsu, S.P.; Pai, M.F.; Peng, Y.S.; Chiang, C.K.; Ho, T.I.; Hung, K.Y. Serum uric acid levels show a 'J-shaped' association with all-cause mortality in haemodialysis patients. Nephrol Dial Transplant 2004 , 19 , 457-462, doi:10.1093/ndt/gfg563. Zawada, A.M.; Carrero, J.J.; Wolf, M.; Feuersenger, A.; Stuard, S.; Gauly, A.; Winter, A.C.; Ramos, R.; Fouque, D.; Canaud, B. Serum uric acid and mortality risk among hemodialysis patients. Kidney international reports 2020 , 5 , 1196-1206. Kimura, Y.; Yanagida, T.; Onda, A.; Tsukui, D.; Hosoyamada, M.; Kono, H. Soluble uric acid promotes atherosclerosis via AMPK (AMP-activated protein kinase)-mediated inflammation. Arteriosclerosis, thrombosis, and vascular biology 2020 , 40 , 570-582. Latif, W.; Karaboyas, A.; Tong, L.; Winchester, J.F.; Arrington, C.J.; Pisoni, R.L.; Marshall, M.R.; Kleophas, W.; Levin, N.W.; Sen, A.; et al. Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis population. Clin J Am Soc Nephrol 2011 , 6 , 2470-2477, doi:10.2215/cjn.00670111. Park, C.; Obi, Y.; Streja, E.; Rhee, C.M.; Catabay, C.J.; Vaziri, N.D.; Kovesdy, C.P.; Kalantar-Zadeh, K. Serum uric acid, protein intake and mortality in hemodialysis patients. Nephrology Dialysis Transplantation 2017 , 32 , 1750-1757. Niu, S.-W.; Lin, H.Y.-H.; Kuo, I.; Zhen, Y.-Y.; Chang, E.-E.; Shen, F.-C.; Chiu, Y.-W.; Chang, J.-M.; Hung, C.-C.; Hwang, S.-J. Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes. Biomedicines 2022 , 10 , 1719. Niu, S.-W.; Hung, C.-C.; Lin, H.Y.-H.; Kuo, I.-C.; Huang, J.-C.; He, J.-S.; Wen, Z.-H.; Liang, P.-I.; Chiu, Y.-W.; Chang, J.-M. Reduced Incidence of Stroke in Patients with Gout Using Benzbromarone. Journal of Personalized Medicine 2022 , 12 , 28. Hemmelgarn, B.R.; Manns, B.J.; Quan, H.; Ghali, W.A. Adapting the Charlson Comorbidity Index for use in patients with ESRD. Am J Kidney Dis 2003 , 42 , 125-132, doi:10.1016/s0272-6386(03)00415-3. Group, H.A.W. Clinical practice guidelines for hemodialysis adequacy, update 2006. American journal of kidney diseases: the official journal of the National Kidney Foundation 2006 , 48 , S2-S90. Pedrini, L.; Kessler, M.; Canaud, B.; Tattersali, J.; Ter Wee, P.; Vanholder, R.; Wanner, C. Section II: Haemodialysis adequacy. Nephrology Dialysis Transplantation 2002 , 17 , 16-31. Jindal, K.; Chan, C.T.; Deziel, C.; Hirsch, D.; Soroka, S.D.; Tonelli, M.; Culleton, B.F. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. Journal of the American Society of Nephrology: JASN 2006 , 17 , S1-27. Juraschek, S.P.; Kovell, L.C.; Miller III, E.R.; Gelber, A.C. Association of kidney disease with prevalent gout in the United States in 1988–1994 and 2007–2010. In Proceedings of the Seminars in arthritis and rheumatism, 2013; pp. 551-561. Halperin Kuhns, V.L.; Woodward, O.M. Sex Differences in Urate Handling. Int J Mol Sci 2020 , 21 , doi:10.3390/ijms21124269. Hsu, S.-P.; Pai, M.-F.; Peng, Y.-S.; Chiang, C.-K.; Ho, T.-I.; Hung, K.-Y. Serum uric acid levels show a ‘J-shaped’association with all-cause mortality in haemodialysis patients. Nephrology dialysis transplantation 2004 , 19 , 457-462. Yang, Y.; Zhou, W.; Wang, Y.; Zhou, R. Gender-specific association between uric acid level and chronic kidney disease in the elderly health checkup population in China. Ren Fail 2019 , 41 , 197-203, doi:10.1080/0886022x.2019.1591994. Yu, K.-H.; Kuo, C.-F.; Luo, S.-F.; See, L.-C.; Chou, I.-J.; Chang, H.-C.; Chiou, M.-J. Risk of end-stage renal disease associated with gout: a nationwide population study. Arthritis research & therapy 2012 , 14 , 1-6. Doualla, M.; Nkeck, J.R.; Halle, M.P.; Kamdem, F.; Agouak, A.I.; Essouma, M.; Lobe, Y.B.; Ashuntantang, G. Assessment of the efficacy of hemodialysis on uric acid clearance in a sub-Saharan African population at the end stage kidney disease. BMC nephrology 2020 , 21 , 1-8. Park, C.; Obi, Y.; Streja, E.; Rhee, C.M.; Catabay, C.J.; Vaziri, N.D.; Kovesdy, C.P.; Kalantar-Zadeh, K. Serum uric acid, protein intake and mortality in hemodialysis patients. Nephrol Dial Transplant 2017 , 32 , 1750-1757, doi:10.1093/ndt/gfw419. Ramirez-Sandoval, J.C.; Madero, M. Treatment of Hyperuricemia in Chronic Kidney Disease. Contrib Nephrol 2018 , 192 , 135-146, doi:10.1159/000484288. Garg, J.P.; Chasan-Taber, S.; Blair, A.; Plone, M.; Bommer, J.; Raggi, P.; Chertow, G.M. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Arthritis Rheum 2005 , 52 , 290-295, doi:10.1002/art.20781. Suliman, M.E.; Johnson, R.J.; García-López, E.; Qureshi, A.R.; Molinaei, H.; Carrero, J.J.; Heimbürger, O.; Bárány, P.; Axelsson, J.; Lindholm, B.; et al. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis 2006 , 48 , 761-771, doi:10.1053/j.ajkd.2006.08.019. Zawada, A.M.; Carrero, J.J.; Wolf, M.; Feuersenger, A.; Stuard, S.; Gauly, A.; Winter, A.C.; Ramos, R.; Fouque, D.; Canaud, B. Serum Uric Acid and Mortality Risk Among Hemodialysis Patients. Kidney Int Rep 2020 , 5 , 1196-1206, doi:10.1016/j.ekir.2020.05.021. Rohn, B.; Jansing, W.; Seibert, F.S.; Pfab, T.; Cinkilic, O.; Paßfall, J.; Schmidt, S.; Babel, N.; Bauer, F.; Westhoff, T.H. Association of hyperuricemia and serum uric acid lowering therapy with mortality in hemodialysis patients. Ren Fail 2020 , 42 , 1067-1075, doi:10.1080/0886022x.2020.1835674. Bae, E.; Cho, H.J.; Shin, N.; Kim, S.M.; Yang, S.H.; Kim, D.K.; Kim, Y.L.; Kang, S.W.; Yang, C.W.; Kim, N.H.; et al. Lower serum uric acid level predicts mortality in dialysis patients. Medicine (Baltimore) 2016 , 95 , e3701, doi:10.1097/md.0000000000003701. Niu, S.-W.; Lin, H.Y.-H.; Kuo, I.-C.; Zhen, Y.-Y.; Chang, E.-E.; Shen, F.-C.; Chiu, Y.-W.; Chang, J.-M.; Hung, C.-C.; Hwang, S.-J. Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes. Biomedicines 2022 , 10 , 1719. Kumagai, T.; Ota, T.; Tamura, Y.; Chang, W.X.; Shibata, S.; Uchida, S. Time to target uric acid to retard CKD progression. Clinical and experimental nephrology 2017 , 21 , 182-192. Johnson, R.J.; Nakagawa, T.; Jalal, D.; Sánchez-Lozada, L.G.; Kang, D.-H.; Ritz, E. Uric acid and chronic kidney disease: which is chasing which? Nephrology Dialysis Transplantation 2013 , 28 , 2221-2228. Hu, G.; Li, J.; Wang, Q.; Wang, C.; Wang, Y.; Gong, T.; Liu, D. J-shaped relationship between serum uric acid levels and the risk of ischemic stroke in high-risk individuals: A hospital-based observational study. Clinical Neurology and Neurosurgery 2020 , 195 , 105906. Kawasoe, S.; Kubozono, T.; Ojima, S.; Kawabata, T.; Miyahara, H.; Tokushige, K.; Ohishi, M. J-shaped curve for the association between serum uric acid levels and the prevalence of blood pressure abnormalities. Hypertension Research 2021 , 44 , 1186-1193, doi:10.1038/s41440-021-00691-5. Kumthekar, G.V.; Mondhe, S.D.; Hedau, S.; Naidu, S.; Chakravarthi, R.M. Reverse Epidemiology for Lipid Disorders in Hemodialysis-Dependent Patients: Role of Dilutional Hypolipidemia. Indian J Nephrol 2022 , 32 , 104-109, doi:10.4103/ijn.IJN_30_20. Tan, Q.-h.; Liu, L.; Huang, Y.-q.; Yu, Y.-l.; Huang, J.-y.; Chen, C.-l.; Tang, S.-t.; Feng, Y.-q. Relationship between change in serum uric acid and ischemic stroke in chinese hypertensive patients. Frontiers in Cardiovascular Medicine 2021 , 8 , 717128. Wu, S.; Pan, Y.; Zhang, N.; Jun, W.Y.; Wang, C.; On Behalf of the Investigators for the Survey on Abnormal Glucose Regulation in Patients With Acute Stroke Across, C. Lower serum uric acid level strongly predict short-term poor functional outcome in acute stroke with normoglycaemia: a cohort study in China. BMC Neurology 2017 , 17 , 21, doi:10.1186/s12883-017-0793-6. Li, G.; Miao, J.; Sun, W.; Song, X.; Lan, Y.; Zhao, X.; Qiu, X.; Zhang, C.; Zhu, Z.; Zhu, S. Lower serum uric acid is associated with post-stroke depression at discharge. Frontiers in Psychiatry 2020 , 11 , 52. Rich, M.W. Uric acid: is it a risk factor for cardiovascular disease? American Journal of Cardiology 2000 , 85 , 1018-1021. Kanbay, M.; Segal, M.; Afsar, B.; Kang, D.-H.; Rodriguez-Iturbe, B.; Johnson, R.J. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart 2013 , 99 , 759-766. Saito, Y.; Tanaka, A.; Node, K.; Kobayashi, Y. Uric acid and cardiovascular disease: a clinical review. Journal of Cardiology 2021 , 78 , 51-57. Zhou, Y.; Fang, L.; Jiang, L.; Wen, P.; Cao, H.; He, W.; Dai, C.; Yang, J. Uric acid induces renal inflammation via activating tubular NF-κB signaling pathway. PloS one 2012 , 7 , e39738. Kurts, C. A crystal-clear mechanism of chronic kidney disease. Kidney International 2013 , 84 , 859-861. Yu, M.-A.; Sánchez-Lozada, L.G.; Johnson, R.J.; Kang, D.-H. Oxidative stress with an activation of the renin–angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. Journal of hypertension 2010 , 28 , 1234-1242. Sánchez-Lozada, L.G.; Lanaspa, M.A.; Cristóbal-García, M.; García-Arroyo, F.; Soto, V.; Cruz-Robles, D.; Nakagawa, T.; Yu, M.A.; Kang, D.-H.; Johnson, R.J. Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. Nephron Experimental Nephrology 2013 , 121 , e71-e78. Zoccali, C.; Maio, R.; Mallamaci, F.; Sesti, G.; Perticone, F. Uric acid and endothelial dysfunction in essential hypertension. Journal of the American Society of Nephrology 2006 , 17 , 1466-1471. Mazzali, M.; Hughes, J.; Kim, Y.-G.; Jefferson, J.A.; Kang, D.-H.; Gordon, K.L.; Lan, H.Y.; Kivlighn, S.; Johnson, R.J. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. hypertension 2001 , 38 , 1101-1106. Rabadi, M.M.; Kuo, M.-C.; Ghaly, T.; Rabadi, S.M.; Weber, M.; Goligorsky, M.S.; Ratliff, B.B. Interaction between uric acid and HMGB1 translocation and release from endothelial cells. American Journal of Physiology-Renal Physiology 2012 , 302 , F730-F741. Corry, D.B.; Eslami, P.; Yamamoto, K.; Nyby, M.D.; Makino, H.; Tuck, M.L. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin–angiotensin system. Journal of hypertension 2008 , 26 , 269-275. Ali, N.; Rahman, S.; Islam, S.; Haque, T.; Molla, N.H.; Sumon, A.H.; Kathak, R.R.; Asaduzzaman, M.; Islam, F.; Mohanto, N.C. The relationship between serum uric acid and lipid profile in Bangladeshi adults. BMC cardiovascular disorders 2019 , 19 , 1-7. Khosla, U.M.; Zharikov, S.; Finch, J.L.; Nakagawa, T.; Roncal, C.; Mu, W.; Krotova, K.; Block, E.R.; Prabhakar, S.; Johnson, R.J. Hyperuricemia induces endothelial dysfunction. Kidney Int 2005 , 67 , 1739-1742, doi:10.1111/j.1523-1755.2005.00273.x. Ginsberg, M.; Kozin, F.; O'malley, M.; McCarty, D. Release of platelet constituents by monosodium urate crystals. The Journal of clinical investigation 1977 , 60 , 999-1007. Shashar, M.; Francis, J.; Chitalia, V. Thrombosis in the uremic milieu--emerging role of "thrombolome". Semin Dial 2015 , 28 , 198-205, doi:10.1111/sdi.12255. Ofori, S.N.; Odia, O.J. Serum uric acid and target organ damage in essential hypertension. Vasc Health Risk Manag 2014 , 10 , 253-261, doi:10.2147/vhrm.S61363. Lee, S.W.; Yang, Y.M.; Kim, H.Y.; Cho, H.; Nam, S.W.; Kim, S.M.; Kwon, S.K. Predialysis Urea Nitrogen Is a Nutritional Marker of Hemodialysis Patients. Chonnam Med J 2022 , 58 , 69-74, doi:10.4068/cmj.2022.58.2.69. Liu, Y.; Coresh, J.; Eustace, J.A.; Longenecker, J.C.; Jaar, B.; Fink, N.E.; Tracy, R.P.; Powe, N.R.; Klag, M.J. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. Jama 2004 , 291 , 451-459, doi:10.1001/jama.291.4.451. Kovesdy, C.P.; Kopple, J.D.; Kalantar-Zadeh, K. Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy1234. The American Journal of Clinical Nutrition 2013 , 97 , 1163-1177, doi:https://doi.org/10.3945/ajcn.112.036418. Domínguez-Zambrano, E.; Pedraza-Chaverri, J.; López-Santos, A.L.; Medina-Campos, O.N.; Cruz-Rivera, C.; Bueno-Hernández, F.; Espinosa-Cuevas, A. Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis. Nutrients 2020 , 12 , doi:10.3390/nu12092600. Nieto, F.J.; Iribarren, C.; Gross, M.D.; Comstock, G.W.; Cutler, R.G. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? Atherosclerosis 2000 , 148 , 131-139. Kim, S.B.; Yang, W.S.; Min, W.K.; Lee, S.K.; Park, J.S. Reduced oxidative stress in hypoalbuminemic CAPD patients. Peritoneal dialysis international 2000 , 20 , 290-294. Maxwell, S.R.J.; Thomason, H.; Sandler, D.; Leguen, C.; Baxter, M.; Thorpe, G.; Jones, A.; Barnett, A. Antioxidant status in patients with uncomplicated insulin‐dependent and non‐insulin‐dependent diabetes mellitus. European journal of clinical investigation 1997 , 27 , 484-490. Tariq, M.A.; Shamim, S.A.; Rana, K.F.; Saeed, A.; Malik, B.H. Serum Uric Acid - Risk Factor for Acute Ischemic Stroke and Poor Outcomes. Cureus 2019 , 11 , e6007, doi:10.7759/cureus.6007. Hink, H.U.; Santanam, N.; Dikalov, S.; McCann, L.; Nguyen, A.D.; Parthasarathy, S.; Harrison, D.G.; Fukai, T. Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity. Arteriosclerosis, thrombosis, and vascular biology 2002 , 22 , 1402-1408. Sautin, Y.Y.; Johnson, R.J. Uric acid: the oxidant-antioxidant paradox. Nucleosides Nucleotides Nucleic Acids 2008 , 27 , 608-619, doi:10.1080/15257770802138558. Additional Declarations No competing interests reported. Supplementary Files Tablessupplement.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4752853","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":337615178,"identity":"1430d924-0db6-4d5e-b9ec-5e9f9ea2eb01","order_by":0,"name":"Sheng-Wen Niu","email":"","orcid":"","institution":"Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sheng-Wen","middleName":"","lastName":"Niu","suffix":""},{"id":337615179,"identity":"896d4b15-fc66-456c-94d5-6375dc5dd7a9","order_by":1,"name":"I-Ching Kuo","email":"","orcid":"","institution":"Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"I-Ching","middleName":"","lastName":"Kuo","suffix":""},{"id":337615180,"identity":"d9c0a8bb-6100-4e3b-8d52-9bb7930d6214","order_by":2,"name":"Yen-Yi Zhen","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yen-Yi","middleName":"","lastName":"Zhen","suffix":""},{"id":337615181,"identity":"4a25a1a1-5f2b-42b5-ad07-71056ff0f8eb","order_by":3,"name":"Eddy Essen Chang","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Eddy","middleName":"Essen","lastName":"Chang","suffix":""},{"id":337615182,"identity":"8d2ab577-5ed5-415c-a668-0f2e987ae4ea","order_by":4,"name":"Cheng-Chung Ting","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cheng-Chung","middleName":"","lastName":"Ting","suffix":""},{"id":337615184,"identity":"3ac65ac7-c9e1-45e3-8f39-5302cc6bb97d","order_by":5,"name":"Hugo You-Hsien Lin","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hugo","middleName":"You-Hsien","lastName":"Lin","suffix":""},{"id":337615186,"identity":"a7388613-8614-4424-8ffc-6b035677a677","order_by":6,"name":"Yi-Wen Chiu","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yi-Wen","middleName":"","lastName":"Chiu","suffix":""},{"id":337615187,"identity":"037d6b1b-055b-4279-adb7-26f1e4345a75","order_by":7,"name":"Jer-Ming Chang","email":"","orcid":"","institution":"Kaohsiung Medical University Hospital, Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jer-Ming","middleName":"","lastName":"Chang","suffix":""},{"id":337615188,"identity":"177d40d9-a33e-41fb-82fa-493826479446","order_by":8,"name":"Shang-Jyh Hwang","email":"","orcid":"","institution":"Kaohsiung Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shang-Jyh","middleName":"","lastName":"Hwang","suffix":""},{"id":337615189,"identity":"3045e07f-4521-43eb-9ff8-3fb8cc0cb98c","order_by":9,"name":"Chi-Chih Hung","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYDACCcYGZgYDGwMwh4cELWlwLRJEaGFgYGZgOEyCFv7ZzY2fCwrOG+vOSGB88LaNoc7gACFL7hxslp5hcNvM7EYCs+HcNgYJgloMJBLbmHkMbtsAtbBJ8wK1mBGp5RxIC/tvUrQcADmMjZkoLRI3EpuleQySjc3OPGyWnHNOQnI/IS38M9Iffub5Y2e47XjywQ9vymz4JRsIaEECjCC1RMTkKBgFo2AUjALCAAAbljo9jc5G4gAAAABJRU5ErkJggg==","orcid":"","institution":"Kaohsiung Medical University","correspondingAuthor":true,"prefix":"","firstName":"Chi-Chih","middleName":"","lastName":"Hung","suffix":""}],"badges":[],"createdAt":"2024-07-17 01:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4752853/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4752853/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62652484,"identity":"54ff0c9b-9b9b-4e05-9619-6cf9e0ced4b5","added_by":"auto","created_at":"2024-08-17 01:01:16","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":111740,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure1.Flowdiagramofthestudypopulation.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4752853/v1/13f22a9a339fe0bc1ec06689.jpg"},{"id":67441247,"identity":"1f50ef2a-c771-4d32-a80f-40874b9bf28d","added_by":"auto","created_at":"2024-10-25 06:02:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1046487,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4752853/v1/4836956c-ad04-4d98-b2a7-7befa011353b.pdf"},{"id":62652485,"identity":"8a3df615-c56e-4fc2-864f-47d9e80e4982","added_by":"auto","created_at":"2024-08-17 01:01:16","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":29570,"visible":true,"origin":"","legend":"","description":"","filename":"Tablessupplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-4752853/v1/e3a5c098d1410b1dfe05c488.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum Uric acid level as an estimated parameter predicts all-cause mortality in patients with hemodialysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProtein-energy wasting (PEW) as a pathological entity, that is characterized by low protein intake and energetic deposits, in brief, contributing to high mortality in the patients who suffer from chronic kidney disease (CKD) and undergo HD [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Actually, the malnutrition or low serum albumin is a risk factor for all-cause mortality in patients with CKD [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] or ESRD patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], which is frequently associated with systemic inflammation. Additionally, high uremic toxin levels in serum are not only a pathological index but also develop a uremic milieu in the CKD patients. Subsequently, the uremic milieu elicits oxidative stress and systemic inflammation both promote vascular aging via endothelial dysfunction and vascular calcification[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Intriguingly, cardiovascular disease and cardiovascular mortality arise in the ESRD patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs PEW arises, higher inflammation and nutritional parameters, such as cholesterol, sugar and UA, in ESRD patients are the pathological causes of mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The statistical relationship of HbA1c levels in serum and all-cause mortality displays a U-shaped curve in HD patients with highest at HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;6.5% or \u0026gt;\u0026thinsp;9%[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Otherwise, relevance of HbA1c and all-cause mortality in HD patients statistically patterns in a J-shaped curve, especially identified in cardiovascular mortality[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Hsuan Chiu et al. also reported a U-shaped association between non high density lipoprotein cholesterol (LDL) with all-cause and cardiovascular mortality in the patients with CKD stage 3\u0026ndash;5[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs mentioned above, serum UA levels is the parameter reflected in both inflammation and nutritional state[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and anti-oxidant response [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] at the same time. It had been documented in literatures that a J-shaped relationship between serum UA levels and all-cause mortality in dialytic patients[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, hyperuricemia represents a marker reporting endothelial injury, which may imply AMP-Activated Protein Kinase-mediated inflammation is the pathological cause linked to atherosclerosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Meanwhile, Walead Latif, et al reported that hyperuricemia or gouty attack in dialysis patients could also be a reflection of the underlying inflammatory state with subsequent increased risk for all-cause and cardiovascular mortality[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The UA, however, is a nutritional factor, and hypouricemia both concerned with malnutrition-inflammation-atherosclerosis (MIA) syndrome[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Contrary to the general population, low serum UA is associated with higher all-cause mortality in dialysis patients, especially in those with PEW [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In the patients with hyperuricemia, they possess higher antioxidant capacity, thereafter less oxidative damage, and better nutritional status are coincident in them [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Former study has evidenced that hyperuricemia can merely predict renal outcome in CKD patients without metabolic syndrome (MS) nor diabetes (DM)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Also, mounting evidences have noted that urate lowering therapy is likely improve incidence of stroke without comorbidities [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Mentioned above, UA elevated in serum signifies elevation of inflammation in patients with less comorbidities and exacerbates overall mortality; but in patients with more comorbidities, the similar repertoire may differently display recovery or nutritional condition and relate to less overall mortality. Several studies have been investigated the relationship between comorbidity and mortality in CKD patients during dialysis, and they widely used Charlson score index (CCI) to predict mortality [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Based on the criteria, the subjects which we collected for this study were mainly categorized to less comorbidities and more comorbidities according to CCI, and we proposed to investigate the relationship between serum UA levels and total mortality in the two individual groups.\u003c/p\u003e \u003cp\u003eThus, we questioned of whether the hyperuricemia is or not a risk factor associated with worse survival in dialysis patients and could comorbidities, surveyed with CCI, modify the effect of hyperuricemia.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eParticipants and design\u003c/p\u003e \u003cp\u003eThe Kaohsiung Hemodialysis Study is a prospective cohort study that examines the quality of patient care based on the HD, surgery, planning, and execution management system developed by the Taiwan Nephrology Society. Between January 1st 1997 and December 31st 2009, HD occurred continuously in three affiliated hospitals of nine related HD clinics at Kaohsiung Medical University in southern Taiwan, with stable HD three times a week for more than 90 days, in patients over 18 years of age. These subjects were collected and followed through May 31st 2013.\u003c/p\u003e \u003cp\u003eAmong them, 94 subjects stopped follow-up within 6 months, and 39 subjects had more than 10% missing data. In this study, the final cohort was 2615 HD incident subjects. According to CCI, subjects were categorized according to the following criteria: CCI\u0026thinsp;\u0026lt;\u0026thinsp;3 (n\u0026thinsp;=\u0026thinsp;1107) and CCI\u0026thinsp;\u0026ge;\u0026thinsp;4 (n\u0026thinsp;=\u0026thinsp;1508) (Fig.\u0026nbsp;1). This study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-G(II)-20160024). We confirmed that informed consent was obtained from all subjects and/or their legal guardians.\u003c/p\u003e \u003cp\u003eDialysis initiation was performed according to the regulations of National Health Insurance (NHI) Administration of Taiwan, which stipulated the required laboratory data, nutritional status, uremic status, and estimated glomerular filtration rate (eGFR). The mean eGFR at the start of dialysis was 4.9 mL/min/1.73 m2, and the mean residual urine was 560 ml. A total of 178 subjects (6.1%) received peritoneal dialysis during the same period. The NHI administration provides full coverage of HD therapy and erythropoiesis stimulating agent therapy at a fixed fee. Attending physicians are rotated between dialysis centers and dialysis machines are involved; artificial kidneys and water management have similar applications.\u003c/p\u003e \u003cp\u003eFurthermore, we do not reduce the surface area of ​​the dialyzer if the KDIGO recommended target URR (70%) or Kt/V (\u0026gt;\u0026thinsp;1.4) is achieved. But if the minimum requirements of URR (\u0026gt;\u0026thinsp;65%) or Kt/V (\u0026gt;\u0026thinsp;1.2) in the Taiwan Nephrology Society guidelines are not met, we will increase the surface area of ​​the dialyzer.\u003c/p\u003e \u003cp\u003eMeasurements\u003c/p\u003e \u003cp\u003eBaseline variables included demographic characteristics (age, sex, and year of enrollment), history of DM, congestive heart failure (CHF), hypertension, stroke, cancer, and hepatitis. We obtained and averaged test results (pre- and post-dialysis body weight (BW)), laboratory data (serum creatinine, post-dialysis blood urea nitrogen (BUN), albumin (methyl bromide) with the Roche cobas\u0026reg; 6000 analyzer Phenol green (BCG) albumin determination), white blood cell count (WBC), heme, total cholesterol, cardiothoracic ratio (CTR), iron saturation and glucose (AC)) and HD parameters (UF/BW ratio, vascular access, Kt/V(Daugirdas), URR and normalized protein catabolic rate (nPCR) between 4th and 9th month). Subjects with DM and hypertension were identified through clinical diagnosis. Laboratory data were recorded monthly, and statistical analysis was performed on average data 6 months after stable dialysis. Assessing dialysis adequacy using the single-cell Daugirdas formula Kt/V\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1n((postBUN/preBUN)\u0026thinsp;\u0026minus;\u0026thinsp;0.008 \u0026times; t) + [(4\u0026thinsp;\u0026minus;\u0026thinsp;3.5 \u0026times; (postBUN/preBUN)) \u0026times; UF/BW] and URR is the ratio of (preBUN\u0026thinsp;\u0026minus;\u0026thinsp;postBUN) as numerator to the denotator preBUN (BUN: mg/dL). Post-dialysis BUN values ​​are described according to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines as follows [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]: (1) the ultrafiltration rate is reset to zero, (2) the blood pump is slowed to 100 mL/min for 10 \u0026minus;\u0026thinsp;20 seconds, ( 3) Then stop the pump and (4) withdraw a sample from the arterial blood line sampling port or from the tubing connected to the arterial needle[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e],[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003cp\u003eBased on the CCI criteria, all subjects were categorized by CCI\u0026thinsp;\u0026lt;\u0026thinsp;3 (n\u0026thinsp;=\u0026thinsp;1107) and CCI\u0026thinsp;\u0026ge;\u0026thinsp;4 (n\u0026thinsp;=\u0026thinsp;1508) (Fig.\u0026nbsp;1). Subjects were followed from month 4 of HD or death to the end of month 20. All-cause mortality was confirmed by review of death certificates using charts or the National Death Index.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eBaseline PA characteristics were assessed as percentages of categorical profiles, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables with approximately normal distribution, and median and six-quartile range for continuous variables with skewed distribution. A Markov chain Monte Carlo method was applied to minimize the effect of missing covariates (seven covariates had less than 5% missing values). Multiple linear regression was used to evaluate the relationship between URR, Kt/V and the significance factors described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The analysis was initially performed without adjustments but were subsequently applied to several sets of covariates stratified in this study. These models also resolved covariates with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis and log-transformed continuous variables with skewed distributions to obtain normal distributions. Age at dialysis initiation, sex, year of entry, DM, hypertension, hepatitis, CHF, post-dialysis BW, nPCR, UF:BW ratio, creatinine, hemoglobin, WBC, albumin, AC, log-transformed cholesterol and phosphorus were recorded in this study. Also tested based on sex, age (\u0026ge;\u0026thinsp;65 years), DM, CHF, hepatitis, hypertension, anemia (heme\u0026thinsp;\u0026lt;\u0026thinsp;10 g/dL), albumin (\u0026lt;\u0026thinsp;3.5 g/dL), UF (mean), and BW (mean value). Interactions between subgroups were examined. A P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 is the threshold for statistical significance. Statistical analyzes were performed using R 4.1.3 software (R Foundation for Statistical Computing, Vienna, Austria) and SPSS version 20.0 (SPSS Inc., Chicago, IL).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data of incident hemodialysis patients in the cohort.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c9\" namest=\"c3\"\u003e \u003cp\u003eUA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8\u0026ndash;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.5\u0026ndash;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.1\u0026ndash;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.7\u0026ndash;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2615\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e428 (16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e448 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e446 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e436 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e425 (16.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e432 (16.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003e-\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e59.1 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.9 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.7 (14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e59.4 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57.7 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.5 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e54.0 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, (female %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1317 (50.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e247 (57.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e267 (59.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e220 (49.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e197 (45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e191 (44.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e195 (45.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e361 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70 (15.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63 (14.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e54 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e850 (32.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121 (28.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e158 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e151 (33.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e115 (26.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e149 (35.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e156 (36.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e439 (16.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63 (14.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e86 (19.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e67 (15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e86 (20.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e76 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e194 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (9.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e28 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30 (7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e27 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.239\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e161 (6.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1261 (48.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e206 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e232 (51.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e238 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e207 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e206 (48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e172 (39.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1831 (70.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e261 (61.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e315 (70.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e327 (73.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e305 (70.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e314 (73.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e309 (71.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson comorbidity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3.9 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.0 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.8 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.0 (1.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.7 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory data\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (x1000/ul)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e7.0 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.0 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.0 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.0 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.9 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.0 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.9 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.6 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.9 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.0 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10.1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.0 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.6 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3.7 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.5 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.7 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.8 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.8 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.8 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.8 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e187.0 (45.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e174.7 (44.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e183.0 (42.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e184.4 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e190.1 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e192.1 (43.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e198.1 (47.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose[AC] (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e136.4 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139.7 (64.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e137.6 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e138.4 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e134.3 (57.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e136.0 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e132.5 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0514\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.2 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.2 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.7 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.1 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.2 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK (mEq/l)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4.7 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.5 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.6 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.7 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.8 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.8 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9.3 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.3 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.3 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.3 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.3 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.3 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9.4 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.486\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e5.0 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.7 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.9 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.2 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.7 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBW post dialysis (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e56.7 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.7 (10.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.2 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56.3 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57.2 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.6 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e61.2 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUF/BW ratio (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3.8 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.7 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.9 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.9 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.9 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.9 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBUN pre-HD (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e70.3 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59.2 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.4 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68.0 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72.2 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e74.8 (17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82.5 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eURR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.7 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKt/V (Gotch)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.3 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.2 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enPCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.2 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.2 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.2 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.2 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac/thoracic ratio (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e50.3 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.5 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.8 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.2 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49.7 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e49.4 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e50.2 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll-cause mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1115 (42.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e247 (57.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e198 (44.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e198 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e162 (37.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e165 (38.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e145 (33.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eWBC: white blood cells, Hb: hemoglobin, K: potassium, Ca: calcium, P: phosphate, BW: body weight, UF: ultrafiltration, BUN: blood urea nitrogen, HD: hemodialysis, URR: urea reduction ratio, nPCR: normalized protein catabolic rate. Data are presented as mean (standard error), median (interquartile range), or count (percentage%). * (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) indicates a significant difference.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEthics declarations\u003c/p\u003e \u003cp\u003e This study was planned to be presented in accordance with the guidelines of the Declaration of Helsinki. In addition, this study was also approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-G(II)-20160024).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; characteristics by UA quintiles\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the baseline clinical and biochemical characteristics of the 2615 participants based on the presence of serum UA levels. The mean ages from the subject cohort were 59.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.2 years old. Moreover, among subjects with UA\u0026thinsp;\u0026lt;\u0026thinsp;5.8 mg/dl was also related to older age, more female, and higher prevalence of DM, lower prevalence of hypertension, higher Charlson comorbidity index (CCI), lower level of albumin, cholesterol, creatinine, potassium, phosphate, BW post dialysis, UF/BW ratio, BUN pre-dialysis and nPCR, higher level of AC-glucose, Kt/V (Gotch) and cardiac/ thoracic ratio, and higher all-cause mortality. Among subjects with UA\u0026thinsp;=\u0026thinsp;7.1\u0026ndash;7.7 mg/dl was also related to the highest level of hemoglobin.\u003c/p\u003e \u003cp\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMultivariate linear regression for UA\u003c/h2\u003e \u003cp\u003eThe results of multivariate linear regression for serum UA (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) indicated that higher UA level is significantly related to male, lower age at dialysis, shorter entry-year, lower prevalence of DM, higher pre-dialytic BW, lower Kt/V (Gotch), higher nPCR, higher albumin level, higher log of cholesterol level, higher phosphate level and higher log of PTH level. Although some parameters are present in different trends of association with UA quintiles in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, CCI and serum UA in the subjects are not in statistical relevance as noted in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate linear regression (Full adjusted model for UA level) (continuous)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI β coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender_(female vs male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.283 to -0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at dialysis (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.012 to -0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEntry year (late vs early)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.324 to -0.099\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.215 to 0.075\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.347\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongestive heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.079 to 0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.115 to 0.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.307 to -0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.062 to 0.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-dialytic body weight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.007 to 0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKt/V (Gotch)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.804 to -0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUF/BW ratio100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.009 to 0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.147\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enPCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.420 to 0.804\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eW.B.C. (1000/ul)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.007 to 0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.052 to 0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.745\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.102 to 0.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.839 to 1.883\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose[AC] (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.001 to 0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.220 to 0.314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal calcium (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.074 to 0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.814\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH hormone log\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.044 to 0.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eUA: uric acid, PTH: parathyroid, other abbreviations are the same as in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Data are presented as in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSerum UA quintiles, sixtiles and clinical outcomes\u003c/h2\u003e \u003cp\u003eIn serum UA quintiles group, in the fully-adjusted Cox regression (Table S2), subgroup of UA\u0026thinsp;=\u0026thinsp;6\u0026ndash;7 mg/dl is statistically related to 39% increase in risk of all-cause mortality (HR: 1.39, 95% CI: 1.06\u0026ndash;1.82) compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;9 mg/dl with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4; and subgroup of UA\u0026thinsp;\u0026gt;\u0026thinsp;9 mg/dl is significantly related to about double increase in risk of all-cause mortality (HR: 1.99, 95% CI: 1.18\u0026ndash;3.36) compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;9 mg/dl with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4.\u003c/p\u003e \u003cp\u003eIn UA sextiles group, in the fully-adjusted Cox regression (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), subgroup of UA\u0026thinsp;\u0026lt;\u0026thinsp;5.8 mg/dl is significantly related to 31% increase in risk of all-cause mortality (HR: 1.31, 95% CI: 1.06\u0026ndash;1.63) compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl with total; subgroup of UA\u0026thinsp;\u0026lt;\u0026thinsp;5.8 mg/dl is significantly related to 53% increase (HR: 1.53, 95% CI: 1.20\u0026ndash;1.95), UA\u0026thinsp;=\u0026thinsp;6.5\u0026ndash;7.1 mg/dl is significantly related to 37% increase (HR: 1.37, 95% CI: 1.08\u0026ndash;1.72), UA\u0026thinsp;=\u0026thinsp;7.7\u0026ndash;8.6 mg/dl is significantly related to 34% increase (HR: 1.34, 95% CI: 1.06\u0026ndash;1.69) in risk of all-cause mortality compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4; subgroup of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl is significantly related to 61% increase in risk of all-cause mortality (HR: 1.61, 95% CI: 1.01\u0026ndash;2.38) compared with of UA\u0026thinsp;=\u0026thinsp;7.1\u0026ndash;7.7 mg/dl with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4. As respect with these results, we pinpointed\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHR of UA sextiles for total mortality, Charson\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;4 and Charson\u0026thinsp;\u0026lt;\u0026thinsp;4 by 2 groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eUA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSextile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8\u0026ndash;6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.5\u0026ndash;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.1\u0026ndash;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.7\u0026ndash;8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;8.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e448\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e436\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e432\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003etotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eunadjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.22 (1.83\u0026ndash;2.69)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.57 (1.29\u0026ndash;1.92)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.48 (1.21\u0026ndash;1.81)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.20 (0.98\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.25 (1.02\u0026ndash;1.54)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003efully-adjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.31 (1.06\u0026ndash;1.63)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09 (0.88\u0026ndash;1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.21 (0.98\u0026ndash;1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.07 (0.86\u0026ndash;1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.20 (0.97\u0026ndash;1.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003echarlson\u0026thinsp;\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eunadjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.67 (2.15\u0026ndash;3.32)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.72 (1.38\u0026ndash;2.15)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.64 (1.32\u0026ndash;2.06)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.39 (1.11\u0026ndash;1.76)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.38 (1.10\u0026ndash;1.74)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003efully-adjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.53 (1.20\u0026ndash;1.95)**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.19 (0.93\u0026ndash;1.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.37 (1.08\u0026ndash;1.72)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.22 (0.96\u0026ndash;1.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.34 (1.06\u0026ndash;1.69)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003echarlson\u0026thinsp;\u0026lt;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eunadjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.88 (1.20\u0026ndash;2.94)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.54 (0.97\u0026ndash;2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.27 (0.79\u0026ndash;2.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.96 (0.57\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.27 (0.79\u0026ndash;2.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003efully-adjusted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.21 (0.75\u0026ndash;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.51 (0.94\u0026ndash;2.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.35 (0.82\u0026ndash;2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.18 (0.69\u0026ndash;2.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.61 (1.01\u0026ndash;2.38)*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eHR: hazard ratio, *:\u0026lt;0.05, **:\u0026lt;0.01, ***:\u0026lt;0.001, other abbreviations are the same as in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Data are presented as in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSerum UA level could be an indicator reported nutritional status in the dialysis subjects with high CCI the comorbidities related systemic inflammation and energetic exhausting, so lower serum UA level is related to higher mortality;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe dialysis subjects with low CCI the comorbidities, serum UA level per se may indirectly reflect inflammation. Therefore, higher serum UA level is related to higher mortality instead.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHyperuricemia (serum UA levels\u0026thinsp;\u0026gt;\u0026thinsp;7 mg/dl in men and \u0026gt;\u0026thinsp;6 mg/dl in women) and gout are both common in CKD because of the progressive loss of eGFR and renal clearance of UA in patients with CKD or ESRD. Reduced serum UA levels compared with subjects without CKD[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In the people without CKD, masculine population has tendency with higher mean serum levels (me/dl) compared to feminine [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In the study of Hung er al.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], there was no gender difference in mean serum UA levels (mg/dl) of maintenance HD patients (7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 in men (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;68) and 7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 in women (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;78), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.329). But in another study with larger cohort (n\u0026thinsp;=\u0026thinsp;4242), the prevalence of hyperuricemia was 22.2%, and it was significantly higher in masculine than in feminine (25.2% vs. 17%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.001)[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In present study, the rate of serum UA level\u0026thinsp;\u0026gt;\u0026thinsp;7 mg/dl in masculin is 54.7% (719/1315), the rate of serum UA level\u0026thinsp;\u0026gt;\u0026thinsp;6 mg/dl in feminine is 48.2% (991/2057) (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), under full adjusted of other variables (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, n\u0026thinsp;=\u0026thinsp;2615), the mean level of UA in feminine is 0.164 mg/dl less than in masculine (95%CI=-0.283 to -0.045, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003cp\u003eA study from Taiwan NHI Research Database has pointed that CKD subjects with gout will progress ESRD and their HR is 1.41 higher than the CKD subjects without gout, which were statistically analyzed in the CKD subjects with age ranged from 45 to 59 years. HR of CKD subjects with gout progressed ESRD is 1.58 comparted to CKD subjects without gout, which is statistically calculated in subjects aged 60 and above [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In contrast, our study highlights that the higher serum UA level, the lower average age is noted (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Under full adjusted, while age is one year elder, serum UA level is 0.008 mg/dl lower (95%CI=-0.012 to -0.004, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This result infers that nutritional status might be the cause.\u003c/p\u003e \u003cp\u003eExcessive BW (OR 0.4 [0.2; 0.9]) and Kt/V urea\u0026thinsp;\u0026lt;\u0026thinsp;1.2 (OR 0.1 [0.04; 0.2]) significantly decreases the efficacy of HD, ant they both easily caused more prevalence of hyperuricemia[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The present study unveiled that under full adjusted, pre-dialysis BW is 1 kg heavier, UA level is 0.012 mg/dl higher (95%CI\u0026thinsp;=\u0026thinsp;0.007 to 0.017, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); Kt/V is 1.0 lower, UA level is 0.524 mg/dl higher (95%CI= -0.804 to -0.243, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Otherwise, serum UA level, albumin level and nPCR all reflect nutritional status, and higher UA level, albumin level and nPCR are related to lower mortality[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In present study, under full adjusted, nPCR is 1 g/kg/day higher, uric acid is 0.612 mg/dl higher (95%CI\u0026thinsp;=\u0026thinsp;0.420 to 0.804, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); albumin level is 1mg/dl higher, UA level is 0.256 mg/dl higher.\u003c/p\u003e \u003cp\u003eHyperuricemia might be one of major contributors for CKD development or progression. Although none of precise cutoff UA value as an available parameter report risk impact for kidney damage, it seemed that elevation of serum UA escalates risk for all-cause-mortalith [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In a randomized clinical cases comparing with sevelamer and calcium-based phosphate binders, sevelamer drug regimen, in turn, can significantly reduce in serum UA amount in CKD patients [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In another Swedish study, after adjustment for phosphate binders and vitamin D treatment, serum UA levels remained significantly associated with plasma KDa phosphate (ρ\u0026thinsp;=\u0026thinsp;0.24; P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and Ca \u0026times; P product values ​​(ρ\u0026thinsp;=\u0026thinsp;0.19; P\u0026thinsp;=\u0026thinsp;0.001)[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In a retrospective cohort study of 16,057 HD subjects treated at 564 NephroCare centers in EMEA (Europe, Middle East, and Africa; n\u0026thinsp;=\u0026thinsp;15,127) and Latin America (n\u0026thinsp;=\u0026thinsp;930), in terms of laboratory parameters, subjects with higher serum UA levels also had higher values ​​for phosphate, albumin, creatinine, total cholesterol, triglycerides, normalized protein catabolic rate (nPCR), and parathyroid hormone[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Our study has revealed that UA level is positive parameter related to serum phosphate level (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Under full adjusted, serum phosphate level is 1 mg/dl higher, the serum UA level is 0.267 mg/dl higher; the level of natural log to PTH is 1 higher, the UA level is 0.123mg/dl higher; the level of natural log to total cholesterol is 1 higher, the serum UA level is 1.361 mg/dl higher (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The correlation between serum UA level and phosphate may attributed to efficacy of HD and nutritional status, as the same as cholesterol.\u003c/p\u003e \u003cp\u003eHyperuricemia is associated with increased morbidity and mortality. Even so, data collected from HD subjects is not totally consistent with subjects with hyperuricemia [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In ESRD patients, total antioxidant capacity was associated with serum UA levels, primarily because of higher serum UA levels[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and lower serum UA levels may result in reduced total antioxidant capacity in subjects undergoing dialysis, although further studies are needed to determine the exact mechanism[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Another study in Taiwan declared that hyperuricemia predicts worse renal outcome only in patients without DM or MS [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. One Taiwanese NHI database study revealed therapy with benzbromarone as uricosuric agents decrease the incidence of stroke especially in patients without or with less comorbidities[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The use of uricosuric agents or xanthine oxidase inhibitors to lower uric acid levels as primary or secondary prevention of cardiovascular disease [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] or renal disease is also the subject of many completed and ongoing clinical trials[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study revealed that the higher mortality rate and lower serum UA levels both are correlated overall in ESRD subjects (compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl), subgroup of UA\u0026thinsp;\u0026lt;\u0026thinsp;5.8 mg/dl is significantly related to 31% increase in risk of all-cause mortality (HR: 1.31, 95% CI: 1.06\u0026ndash;1.63) as sextiles (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In comparison with of UA\u0026thinsp;\u0026gt;\u0026thinsp;9.0 mg/dl, none of statistic significant difference exists in risk of all-cause mortality in other subgroup of different UA levels as quintiles (table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). In former studies, Hsu et al. reported that \u0026lsquo;low level\u0026rsquo; and \u0026lsquo;high level\u0026rsquo; groups serum represent higher risk of mortality than those in the \u0026lsquo;average level\u0026rsquo; group in 2004 as taking insight into UA levels in ESRD patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In 2020, Zawada el al. stated that the relationship of serum UA and all-cause mortality exhibits in U-shaped pattern in a retrospective cohort study of 16,057 HD subjects treated during 2007 to 2016 in NephroCare centers as documented in the European Clinical Database (EuCliD) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Alternatively, Hu et al. had reported that relationship between serum UA levels and the risk of ischemic stroke displays a J-shaped in another hospital-based cross-sectional study with 2,195 individuals in 2020 [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Additionally, S Kawasoe \u003cem\u003eet al\u003c/em\u003e study reported that relationship between serum UA level and hypertension represent the similar \u0026lsquo;J-shaped\u0026rsquo; in a cohort of 236,221 subjects (age, 56.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0 years; 107,146 men) in 2021. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Similarly, relationship of dialysis subjects and lipid and cardiovascular mortality is a J-shaped pattern in reverse epidemiology (lower lipid levels and higher vascular events compared to general population) in 2022 [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Documented literature implies that the higher serum UA level is an elevated risk for ischemic stroke among patients with hypertension [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. When the subjects have drug regimen \u0026ldquo;uricosuric agents\u0026rdquo; to reduce serum UA level, incidence of stroke would be lower [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Interestingly, the stroke patients would get poor recovery including short-term poor functional outcome, when they have lower serum UA level [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e] and post-stroke depression[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Herein, we bring up a hypothesis: relationship of serum UA and mortality in \u0026ldquo;high level\u0026rdquo; and \u0026ldquo;low level\u0026rdquo; are distinguished in patients with fewer comorbidities and more comorbidities. Lower serum UA in patients with more comorbidities and higher serum UA in patients with fewer comorbidities both trend toward higher mortality. We noticed different variant, CCI, that leads to higher mortality between higher levels and lower levels of serum UA. In respect to serum UA level and mortality in ESRD patients, we found that high UA level was associated with high mortality with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4; and contrarily low UA level was associated with high mortality with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4.\u003c/p\u003e \u003cp\u003eIn the present study, the higher mortality rate associated with higher serum UA levels with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4 (subgroup of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl is significantly related to 61% increase in risk of all-cause mortality (HR: 1.61, 95% CI: 1.01\u0026ndash;2.38) compared with of UA\u0026thinsp;=\u0026thinsp;7.1\u0026ndash;7.7 mg/dl as sextiles in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; and subgroup of UA\u0026thinsp;\u0026gt;\u0026thinsp;9.0 mg/dl is significantly related to about double in risk of all-cause mortality (HR: 1.99, 95% CI: 1.18\u0026ndash;3.36) compared with of UA\u0026thinsp;=\u0026thinsp;7.0\u0026ndash;8.0 mg/dl as quintiles in table S3). It has been well known that serum UA levels correlate with many cardiovascular diseases [\u003cspan additionalcitationids=\"CR46\" citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e] or renal injury without or with less comorbidities[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], including older age, male gender and hypertension. In our study, we evidenced significant differences in serum UA levels between masculine and feminine (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as between hypertensive and non-hypertensive patients (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0235). There was also significantly negative correlation (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between patient age and serum UA levels, and it is considered that there are less comorbidities in the younger. The serum UA levels as a risk factor for kidneyinjury [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] or atherogenic factor as a number of in vitro and in vivo studies reported the UA crystal can cause renal inflammation[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e], oxidative stress[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e], endothelial lesion [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e], hypertension[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], and activate RAAS[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e] to provoke cardiovascular disease or renal disease. Elevating serum UA level promotes oxygenation of LDL and increases lipid peroxidation[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e], and production of oxygen free radicals (ROS) with subsequent endothelial dysfunction[\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. The hyperuricemia may lead to the progression of atherosclerosis[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. High serum UA levels are associated with increased platelet adhesiveness[\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e] followed by thrombi formation in HD patients[\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. Past study also unveiled that hyperuricemia increases cardiovascular risk in patients with hypertension[\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e]. Although higher serum UA level was not associated with more risk of ischemic heart disease and stroke (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), but associated with more risk of hypertension significantly in this study (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0235, Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Therefore, it is possible that higher levels of serum UA reflect status of inflammation and may be related to endothelial dysfunction, hypertension and cardiovascular disease in our HD patients with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4. But the most important, we should not restrict nutrient supply in those with high UA and high comorbidities.\u003c/p\u003e \u003cp\u003eOn the contrary, the higher mortality rate associated with lower serum UA levels with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4 (compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;8.6 mg/dl, subgroup of UA\u0026thinsp;\u0026lt;\u0026thinsp;5.8 mg/dl is significantly related to 53% increase in risk of all-cause mortality (HR: 1.53, 95% CI: 1.20\u0026ndash;1.95), UA\u0026thinsp;=\u0026thinsp;6.5\u0026ndash;7.1 is significantly related to 37% increase in risk of all-cause mortality (HR: 1.37, 95% CI: 1.08\u0026ndash;1.72), and UA\u0026thinsp;=\u0026thinsp;7.7\u0026ndash;8.6 is significantly related to 34% increase in risk of all-cause mortality (HR: 1.34, 95% CI: 1.06\u0026ndash;1.69) as sextiles in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; compared with of UA\u0026thinsp;\u0026gt;\u0026thinsp;9.0 mg/dl, subgroup of UA\u0026thinsp;=\u0026thinsp;6.0\u0026ndash;7.0 mg/dl is significantly related to 39% increase in risk of all-cause mortality (HR: 1.39, 95% CI: 1.06\u0026ndash;1.82) as quintiles in table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). There are also some additional hypotheses that explain the lower mortality rates associated with the higher serum uric acid levels. A low serum level of UA may have been an indicator of malnutrition in the patients[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], just like Pre-dialysis BUN[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e], lipid profiles[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e] are both regarded as indicators of nutritional status in dialysis patients, and low UA levels[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and pre-dialytic BUN levels[\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e] are often surrogates of inadequate protein intake. Protein-energy wasting (PEW), referred to uremic malnutrition, is caused by inadequate nutrient intake, nutrient loss during dialysis, hyper-catabolism associated with dialysis[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Uric acid is an end product of protein metabolism, so PEW leads to low BMI hypocholesterolemia, low level of pre-dialytic BUN and even low level of uric acid[\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. The nPCR is another well-recognized nutrition parameter. In our study, serum UA levels were significantly correlated with both pre-dialysis BUN (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001, Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and nPCR (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.621, \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001, Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These findings suggest that serum UA is a alternative marker of protein intake. Lower serum UA levels are associated with lower antioxidant capacity, and elevated UA levels may reduce oxidative damage associated with atherosclerosis and aging in humans[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e]. Kim \u003cem\u003eet al.\u003c/em\u003e found that better antioxidant capacity was correlated with higher levels of serum UA in peritoneal dialysis patients[\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]. UA also contributes up to 60% to the free radical removal capacity of blood[\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e] and its concentration increases significantly during stroke[\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]. Therefore, in addition to inflammatory factors, UA also has important \u003cem\u003ein vivo\u003c/em\u003e[\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e] and \u003cem\u003ein vitro\u003c/em\u003e[\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e] antioxidant properties. High concentrations of circulating urate are considered one of the major antioxidants in plasma, protecting cells from oxidative damage, thereby helping to extend human lifespan and reduce the risk of cancer[\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]. Therefore, it is possible that lower levels of serum uric acid reflect status of malnutrition and result in reduced total antioxidant capacity in our HD patients with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4. However, we need further studies to clarify above paradoxical issues in HD patients with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4 and \u0026ge;\u0026thinsp;4.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study included HD patients and measured mean dialysis dose between months 4 and 9 of HD. This may have prevented survival bias and ensured stable measurement of dialysis dose. This study has its limitations. First, this is an observational study and cannot establish a causal relationship between SUA, CCI, and clinical outcomes. Second, some other data are lacking, such as residual urine, blood pressure, medications, and body mass index. Third, Kt, BSA, and TEE records are missing, so comparison with Kt/V is not possible. Last, clinical relevance is important because inflammation and malnutrition have pathological impacts and we did not prove inflammation in any way.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, low UA levels of serum uric acid in our HD patients were associated with worse mortality with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4; paradoxically, high levels were associated with worse mortality with CCI\u0026thinsp;\u0026lt;\u0026thinsp;4. High UA was not a risk in those with CCI\u0026thinsp;\u0026ge;\u0026thinsp;4, but low UA should be prevented in all HD patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.-W.N., C.-C.H., H.Y.-Y.L., I.-C.K., Y.-W.C., J.-M. C. and S.-J. H. made the conceptualization. S.-W.N., C.-C.H., Y.-Y.Z., E.E.C., C.-T.C., J.-M.C. and S.-J.H. wrote the methodology. C.-C.H., and Y.-Y.Z. supplied the software. S.-W. N., H.Y.-Y.L. and C.-T.C. made the validation. H.Y.-Y.L. and Y.-Y.Z. made the formal analysis. S.-W. N., C.-C. H., H.Y.-Y.L., I.-C.K., Y.-Y.Z., E.E.C., Y.-W. C., J.-M. C. and S.-J. H. made the investigation. H.Y.-Y.L. and C.-C.H. supplied the resources. S.-W.N., C.-C.H. and Y.-Y.Z. wrote the original draft preparation. S.-W.N., H.-Y.L., C.-C.H., Y.-Y.Z., E.E.C., C.-T.C., and S.-J.H. wrote the review and editing. E.E.C. H.Y.-Y.L. and C.-C.H. made the visualization. Y.-W.C., J.-M.C. and S.-J.H. made the supervision. H.Y.-Y. L., C.-C.H. and S.-J. H. made the project administration. S.-J. H supplied the funding acquisition. All authors reviewed and agreed to publish the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from Kaohsiung Municipal Ta-Tung Hospital (KMTTH-110-005, KMTTH-111-017, KMTTH-112-003),\u0026nbsp;Kaohsiung Medical University Research Foundation (KMU-QA109001), NSYSU-KMU JOINT RESEARCH PROJECT (#NSYSUKMU 110-P008), and\u0026nbsp;Ministry of Science and Technology (MOST-107-2314-B-037-071-,\u0026nbsp;MOST 109-2314-B-037-092-, MOST 109-2314-B-037-094-, MOST 110-2314-B-037-068-MY3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u0026nbsp;\u003c/strong\u003eWritten informed consent has been obtained from the patient(s) to publish this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eThe datasets used and analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ede Mutsert, R.; Grootendorst, D.C.; Axelsson, J.; Boeschoten, E.W.; Krediet, R.T.; Dekker, F.W.; Group, N.S. Excess mortality due to interaction between protein-energy wasting, inflammation and cardiovascular disease in chronic dialysis patients. \u003cem\u003eNephrology Dialysis Transplantation \u003c/em\u003e\u003cstrong\u003e2008\u003c/strong\u003e, \u003cem\u003e23\u003c/em\u003e, 2957-2964.\u003c/li\u003e\n\u003cli\u003eSong, H.; Wei, C.; Hu, H.; Wan, Q. Association of the serum albumin level with prognosis in chronic kidney disease patients. \u003cem\u003eInt Urol Nephrol \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e54\u003c/em\u003e, 2421-2431, doi:10.1007/s11255-022-03140-5.\u003c/li\u003e\n\u003cli\u003eHao, N.; Cheng, B.C.; Yang, H.T.; Wu, C.H.; Lei, Y.Y.; Chao, M.C.; Wang, P.Y.; Kuo, L.C.; Moi, S.H.; Yang, C.H.; et al. Time-varying serum albumin levels and all-cause mortality in prevalent peritoneal dialysis patients: a 5-year observational study. \u003cem\u003eBMC Nephrol \u003c/em\u003e\u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e20\u003c/em\u003e, 254, doi:10.1186/s12882-019-1433-8.\u003c/li\u003e\n\u003cli\u003eDonato, A.J.; Morgan, R.G.; Walker, A.E.; Lesniewski, L.A. Cellular and molecular biology of aging endothelial cells. \u003cem\u003eJournal of molecular and cellular cardiology \u003c/em\u003e\u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e89\u003c/em\u003e, 122-135.\u003c/li\u003e\n\u003cli\u003eAlves, F.C.; Sun, J.; Qureshi, A.R.; Dai, L.; Snaedal, S.; Barany, P.; Heimb\u0026uuml;rger, O.; Lindholm, B.; Stenvinkel, P. The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease. \u003cem\u003ePloS one \u003c/em\u003e\u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e13\u003c/em\u003e, e0190410.\u003c/li\u003e\n\u003cli\u003eDom\u0026iacute;nguez-Zambrano, E.; Pedraza-Chaverri, J.; L\u0026oacute;pez-Santos, A.L.; Medina-Campos, O.N.; Cruz-Rivera, C.; Bueno-Hern\u0026aacute;ndez, F.; Espinosa-Cuevas, A. Association between serum uric acid levels, nutritional and antioxidant status in patients on hemodialysis. \u003cem\u003eNutrients \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e, 2600.\u003c/li\u003e\n\u003cli\u003eAl-Ghamdi, S.M.; Bieber, B.; AlRukhaimi, M.; AlSahow, A.; Al Salmi, I.; Al Ali, F.; Al Aradi, A.; Pecoits-Filho, R.; Robinson, B.M.; Pisoni, R.L. Diabetes Prevalence, Treatment, Control, and Outcomes Among Hemodialysis Patients in the Gulf Cooperation Council Countries. \u003cem\u003eKidney international reports \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e7\u003c/em\u003e, 1093-1102.\u003c/li\u003e\n\u003cli\u003eRaghavan, S.; Vassy, J.L.; Ho, Y.L.; Song, R.J.; Gagnon, D.R.; Cho, K.; Wilson, P.W.; Phillips, L.S. Diabetes mellitus\u0026ndash;related all‐cause and cardiovascular mortality in a national cohort of adults. \u003cem\u003eJournal of the American Heart Association \u003c/em\u003e\u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e8\u003c/em\u003e, e011295.\u003c/li\u003e\n\u003cli\u003eChiu, H.; Wu, P.-Y.; Huang, J.-C.; Tu, H.-P.; Lin, M.-Y.; Chen, S.-C.; Chang, J.-M. There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3\u0026ndash;5. \u003cem\u003eScientific Reports \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e, 12749.\u003c/li\u003e\n\u003cli\u003eStamp, L.; Dalbeth, N. Urate-lowering therapy for asymptomatic hyperuricaemia: a need for caution. In Proceedings of the Seminars in Arthritis and Rheumatism, 2017; pp. 457-464.\u003c/li\u003e\n\u003cli\u003eKim, S.B.; Yang, W.S.; Min, W.K.; Lee, S.K.; Park, J.S. Reduced oxidative stress in hypoalbuminemic CAPD patients. \u003cem\u003ePerit Dial Int \u003c/em\u003e\u003cstrong\u003e2000\u003c/strong\u003e, \u003cem\u003e20\u003c/em\u003e, 290-294.\u003c/li\u003e\n\u003cli\u003eHsu, S.P.; Pai, M.F.; Peng, Y.S.; Chiang, C.K.; Ho, T.I.; Hung, K.Y. Serum uric acid levels show a \u0026apos;J-shaped\u0026apos; association with all-cause mortality in haemodialysis patients. \u003cem\u003eNephrol Dial Transplant \u003c/em\u003e\u003cstrong\u003e2004\u003c/strong\u003e, \u003cem\u003e19\u003c/em\u003e, 457-462, doi:10.1093/ndt/gfg563.\u003c/li\u003e\n\u003cli\u003eZawada, A.M.; Carrero, J.J.; Wolf, M.; Feuersenger, A.; Stuard, S.; Gauly, A.; Winter, A.C.; Ramos, R.; Fouque, D.; Canaud, B. Serum uric acid and mortality risk among hemodialysis patients. \u003cem\u003eKidney international reports \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e5\u003c/em\u003e, 1196-1206.\u003c/li\u003e\n\u003cli\u003eKimura, Y.; Yanagida, T.; Onda, A.; Tsukui, D.; Hosoyamada, M.; Kono, H. Soluble uric acid promotes atherosclerosis via AMPK (AMP-activated protein kinase)-mediated inflammation. \u003cem\u003eArteriosclerosis, thrombosis, and vascular biology \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e40\u003c/em\u003e, 570-582.\u003c/li\u003e\n\u003cli\u003eLatif, W.; Karaboyas, A.; Tong, L.; Winchester, J.F.; Arrington, C.J.; Pisoni, R.L.; Marshall, M.R.; Kleophas, W.; Levin, N.W.; Sen, A.; et al. Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis population. \u003cem\u003eClin J Am Soc Nephrol \u003c/em\u003e\u003cstrong\u003e2011\u003c/strong\u003e, \u003cem\u003e6\u003c/em\u003e, 2470-2477, doi:10.2215/cjn.00670111.\u003c/li\u003e\n\u003cli\u003ePark, C.; Obi, Y.; Streja, E.; Rhee, C.M.; Catabay, C.J.; Vaziri, N.D.; Kovesdy, C.P.; Kalantar-Zadeh, K. Serum uric acid, protein intake and mortality in hemodialysis patients. \u003cem\u003eNephrology Dialysis Transplantation \u003c/em\u003e\u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e32\u003c/em\u003e, 1750-1757.\u003c/li\u003e\n\u003cli\u003eNiu, S.-W.; Lin, H.Y.-H.; Kuo, I.; Zhen, Y.-Y.; Chang, E.-E.; Shen, F.-C.; Chiu, Y.-W.; Chang, J.-M.; Hung, C.-C.; Hwang, S.-J. Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes. \u003cem\u003eBiomedicines \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e, 1719.\u003c/li\u003e\n\u003cli\u003eNiu, S.-W.; Hung, C.-C.; Lin, H.Y.-H.; Kuo, I.-C.; Huang, J.-C.; He, J.-S.; Wen, Z.-H.; Liang, P.-I.; Chiu, Y.-W.; Chang, J.-M. Reduced Incidence of Stroke in Patients with Gout Using Benzbromarone. \u003cem\u003eJournal of Personalized Medicine \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e, 28.\u003c/li\u003e\n\u003cli\u003eHemmelgarn, B.R.; Manns, B.J.; Quan, H.; Ghali, W.A. Adapting the Charlson Comorbidity Index for use in patients with ESRD. \u003cem\u003eAm J Kidney Dis \u003c/em\u003e\u003cstrong\u003e2003\u003c/strong\u003e, \u003cem\u003e42\u003c/em\u003e, 125-132, doi:10.1016/s0272-6386(03)00415-3.\u003c/li\u003e\n\u003cli\u003eGroup, H.A.W. Clinical practice guidelines for hemodialysis adequacy, update 2006. \u003cem\u003eAmerican journal of kidney diseases: the official journal of the National Kidney Foundation \u003c/em\u003e\u003cstrong\u003e2006\u003c/strong\u003e, \u003cem\u003e48\u003c/em\u003e, S2-S90.\u003c/li\u003e\n\u003cli\u003ePedrini, L.; Kessler, M.; Canaud, B.; Tattersali, J.; Ter Wee, P.; Vanholder, R.; Wanner, C. Section II: Haemodialysis adequacy. \u003cem\u003eNephrology Dialysis Transplantation \u003c/em\u003e\u003cstrong\u003e2002\u003c/strong\u003e, \u003cem\u003e17\u003c/em\u003e, 16-31.\u003c/li\u003e\n\u003cli\u003eJindal, K.; Chan, C.T.; Deziel, C.; Hirsch, D.; Soroka, S.D.; Tonelli, M.; Culleton, B.F. Hemodialysis clinical practice guidelines for the Canadian Society of Nephrology. \u003cem\u003eJournal of the American Society of Nephrology: JASN \u003c/em\u003e\u003cstrong\u003e2006\u003c/strong\u003e, \u003cem\u003e17\u003c/em\u003e, S1-27.\u003c/li\u003e\n\u003cli\u003eJuraschek, S.P.; Kovell, L.C.; Miller III, E.R.; Gelber, A.C. Association of kidney disease with prevalent gout in the United States in 1988\u0026ndash;1994 and 2007\u0026ndash;2010. In Proceedings of the Seminars in arthritis and rheumatism, 2013; pp. 551-561.\u003c/li\u003e\n\u003cli\u003eHalperin Kuhns, V.L.; Woodward, O.M. Sex Differences in Urate Handling. \u003cem\u003eInt J Mol Sci \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e21\u003c/em\u003e, doi:10.3390/ijms21124269.\u003c/li\u003e\n\u003cli\u003eHsu, S.-P.; Pai, M.-F.; Peng, Y.-S.; Chiang, C.-K.; Ho, T.-I.; Hung, K.-Y. Serum uric acid levels show a \u0026lsquo;J-shaped\u0026rsquo;association with all-cause mortality in haemodialysis patients. \u003cem\u003eNephrology dialysis transplantation \u003c/em\u003e\u003cstrong\u003e2004\u003c/strong\u003e, \u003cem\u003e19\u003c/em\u003e, 457-462.\u003c/li\u003e\n\u003cli\u003eYang, Y.; Zhou, W.; Wang, Y.; Zhou, R. Gender-specific association between uric acid level and chronic kidney disease in the elderly health checkup population in China. \u003cem\u003eRen Fail \u003c/em\u003e\u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e41\u003c/em\u003e, 197-203, doi:10.1080/0886022x.2019.1591994.\u003c/li\u003e\n\u003cli\u003eYu, K.-H.; Kuo, C.-F.; Luo, S.-F.; See, L.-C.; Chou, I.-J.; Chang, H.-C.; Chiou, M.-J. Risk of end-stage renal disease associated with gout: a nationwide population study. \u003cem\u003eArthritis research \u0026amp; therapy \u003c/em\u003e\u003cstrong\u003e2012\u003c/strong\u003e, \u003cem\u003e14\u003c/em\u003e, 1-6.\u003c/li\u003e\n\u003cli\u003eDoualla, M.; Nkeck, J.R.; Halle, M.P.; Kamdem, F.; Agouak, A.I.; Essouma, M.; Lobe, Y.B.; Ashuntantang, G. Assessment of the efficacy of hemodialysis on uric acid clearance in a sub-Saharan African population at the end stage kidney disease. \u003cem\u003eBMC nephrology \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e21\u003c/em\u003e, 1-8.\u003c/li\u003e\n\u003cli\u003ePark, C.; Obi, Y.; Streja, E.; Rhee, C.M.; Catabay, C.J.; Vaziri, N.D.; Kovesdy, C.P.; Kalantar-Zadeh, K. Serum uric acid, protein intake and mortality in hemodialysis patients. \u003cem\u003eNephrol Dial Transplant \u003c/em\u003e\u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e32\u003c/em\u003e, 1750-1757, doi:10.1093/ndt/gfw419.\u003c/li\u003e\n\u003cli\u003eRamirez-Sandoval, J.C.; Madero, M. Treatment of Hyperuricemia in Chronic Kidney Disease. \u003cem\u003eContrib Nephrol \u003c/em\u003e\u003cstrong\u003e2018\u003c/strong\u003e, \u003cem\u003e192\u003c/em\u003e, 135-146, doi:10.1159/000484288.\u003c/li\u003e\n\u003cli\u003eGarg, J.P.; Chasan-Taber, S.; Blair, A.; Plone, M.; Bommer, J.; Raggi, P.; Chertow, G.M. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. \u003cem\u003eArthritis Rheum \u003c/em\u003e\u003cstrong\u003e2005\u003c/strong\u003e, \u003cem\u003e52\u003c/em\u003e, 290-295, doi:10.1002/art.20781.\u003c/li\u003e\n\u003cli\u003eSuliman, M.E.; Johnson, R.J.; Garc\u0026iacute;a-L\u0026oacute;pez, E.; Qureshi, A.R.; Molinaei, H.; Carrero, J.J.; Heimb\u0026uuml;rger, O.; B\u0026aacute;r\u0026aacute;ny, P.; Axelsson, J.; Lindholm, B.; et al. J-shaped mortality relationship for uric acid in CKD. \u003cem\u003eAm J Kidney Dis \u003c/em\u003e\u003cstrong\u003e2006\u003c/strong\u003e, \u003cem\u003e48\u003c/em\u003e, 761-771, doi:10.1053/j.ajkd.2006.08.019.\u003c/li\u003e\n\u003cli\u003eZawada, A.M.; Carrero, J.J.; Wolf, M.; Feuersenger, A.; Stuard, S.; Gauly, A.; Winter, A.C.; Ramos, R.; Fouque, D.; Canaud, B. Serum Uric Acid and Mortality Risk Among Hemodialysis Patients. \u003cem\u003eKidney Int Rep \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e5\u003c/em\u003e, 1196-1206, doi:10.1016/j.ekir.2020.05.021.\u003c/li\u003e\n\u003cli\u003eRohn, B.; Jansing, W.; Seibert, F.S.; Pfab, T.; Cinkilic, O.; Pa\u0026szlig;fall, J.; Schmidt, S.; Babel, N.; Bauer, F.; Westhoff, T.H. Association of hyperuricemia and serum uric acid lowering therapy with mortality in hemodialysis patients. \u003cem\u003eRen Fail \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e42\u003c/em\u003e, 1067-1075, doi:10.1080/0886022x.2020.1835674.\u003c/li\u003e\n\u003cli\u003eBae, E.; Cho, H.J.; Shin, N.; Kim, S.M.; Yang, S.H.; Kim, D.K.; Kim, Y.L.; Kang, S.W.; Yang, C.W.; Kim, N.H.; et al. Lower serum uric acid level predicts mortality in dialysis patients. \u003cem\u003eMedicine (Baltimore) \u003c/em\u003e\u003cstrong\u003e2016\u003c/strong\u003e, \u003cem\u003e95\u003c/em\u003e, e3701, doi:10.1097/md.0000000000003701.\u003c/li\u003e\n\u003cli\u003eNiu, S.-W.; Lin, H.Y.-H.; Kuo, I.-C.; Zhen, Y.-Y.; Chang, E.-E.; Shen, F.-C.; Chiu, Y.-W.; Chang, J.-M.; Hung, C.-C.; Hwang, S.-J. Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes. \u003cem\u003eBiomedicines \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e, 1719.\u003c/li\u003e\n\u003cli\u003eKumagai, T.; Ota, T.; Tamura, Y.; Chang, W.X.; Shibata, S.; Uchida, S. Time to target uric acid to retard CKD progression. \u003cem\u003eClinical and experimental nephrology \u003c/em\u003e\u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e21\u003c/em\u003e, 182-192.\u003c/li\u003e\n\u003cli\u003eJohnson, R.J.; Nakagawa, T.; Jalal, D.; S\u0026aacute;nchez-Lozada, L.G.; Kang, D.-H.; Ritz, E. Uric acid and chronic kidney disease: which is chasing which? \u003cem\u003eNephrology Dialysis Transplantation \u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 2221-2228.\u003c/li\u003e\n\u003cli\u003eHu, G.; Li, J.; Wang, Q.; Wang, C.; Wang, Y.; Gong, T.; Liu, D. J-shaped relationship between serum uric acid levels and the risk of ischemic stroke in high-risk individuals: A hospital-based observational study. \u003cem\u003eClinical Neurology and Neurosurgery \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e195\u003c/em\u003e, 105906.\u003c/li\u003e\n\u003cli\u003eKawasoe, S.; Kubozono, T.; Ojima, S.; Kawabata, T.; Miyahara, H.; Tokushige, K.; Ohishi, M. J-shaped curve for the association between serum uric acid levels and the prevalence of blood pressure abnormalities. \u003cem\u003eHypertension Research \u003c/em\u003e\u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e44\u003c/em\u003e, 1186-1193, doi:10.1038/s41440-021-00691-5.\u003c/li\u003e\n\u003cli\u003eKumthekar, G.V.; Mondhe, S.D.; Hedau, S.; Naidu, S.; Chakravarthi, R.M. Reverse Epidemiology for Lipid Disorders in Hemodialysis-Dependent Patients: Role of Dilutional Hypolipidemia. \u003cem\u003eIndian J Nephrol \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e32\u003c/em\u003e, 104-109, doi:10.4103/ijn.IJN_30_20.\u003c/li\u003e\n\u003cli\u003eTan, Q.-h.; Liu, L.; Huang, Y.-q.; Yu, Y.-l.; Huang, J.-y.; Chen, C.-l.; Tang, S.-t.; Feng, Y.-q. Relationship between change in serum uric acid and ischemic stroke in chinese hypertensive patients. \u003cem\u003eFrontiers in Cardiovascular Medicine \u003c/em\u003e\u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e8\u003c/em\u003e, 717128.\u003c/li\u003e\n\u003cli\u003eWu, S.; Pan, Y.; Zhang, N.; Jun, W.Y.; Wang, C.; On Behalf of the Investigators for the Survey on Abnormal Glucose Regulation in Patients With Acute Stroke Across, C. Lower serum uric acid level strongly predict short-term poor functional outcome in acute stroke with normoglycaemia: a cohort study in China. \u003cem\u003eBMC Neurology \u003c/em\u003e\u003cstrong\u003e2017\u003c/strong\u003e, \u003cem\u003e17\u003c/em\u003e, 21, doi:10.1186/s12883-017-0793-6.\u003c/li\u003e\n\u003cli\u003eLi, G.; Miao, J.; Sun, W.; Song, X.; Lan, Y.; Zhao, X.; Qiu, X.; Zhang, C.; Zhu, Z.; Zhu, S. Lower serum uric acid is associated with post-stroke depression at discharge. \u003cem\u003eFrontiers in Psychiatry \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e, 52.\u003c/li\u003e\n\u003cli\u003eRich, M.W. Uric acid: is it a risk factor for cardiovascular disease? \u003cem\u003eAmerican Journal of Cardiology \u003c/em\u003e\u003cstrong\u003e2000\u003c/strong\u003e, \u003cem\u003e85\u003c/em\u003e, 1018-1021.\u003c/li\u003e\n\u003cli\u003eKanbay, M.; Segal, M.; Afsar, B.; Kang, D.-H.; Rodriguez-Iturbe, B.; Johnson, R.J. The role of uric acid in the pathogenesis of human cardiovascular disease. \u003cem\u003eHeart \u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e99\u003c/em\u003e, 759-766.\u003c/li\u003e\n\u003cli\u003eSaito, Y.; Tanaka, A.; Node, K.; Kobayashi, Y. Uric acid and cardiovascular disease: a clinical review. \u003cem\u003eJournal of Cardiology \u003c/em\u003e\u003cstrong\u003e2021\u003c/strong\u003e, \u003cem\u003e78\u003c/em\u003e, 51-57.\u003c/li\u003e\n\u003cli\u003eZhou, Y.; Fang, L.; Jiang, L.; Wen, P.; Cao, H.; He, W.; Dai, C.; Yang, J. Uric acid induces renal inflammation via activating tubular NF-\u0026kappa;B signaling pathway. \u003cem\u003ePloS one \u003c/em\u003e\u003cstrong\u003e2012\u003c/strong\u003e, \u003cem\u003e7\u003c/em\u003e, e39738.\u003c/li\u003e\n\u003cli\u003eKurts, C. A crystal-clear mechanism of chronic kidney disease. \u003cem\u003eKidney International \u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e84\u003c/em\u003e, 859-861.\u003c/li\u003e\n\u003cli\u003eYu, M.-A.; S\u0026aacute;nchez-Lozada, L.G.; Johnson, R.J.; Kang, D.-H. Oxidative stress with an activation of the renin\u0026ndash;angiotensin system in human vascular endothelial cells as a novel mechanism of uric acid-induced endothelial dysfunction. \u003cem\u003eJournal of hypertension \u003c/em\u003e\u003cstrong\u003e2010\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 1234-1242.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez-Lozada, L.G.; Lanaspa, M.A.; Crist\u0026oacute;bal-Garc\u0026iacute;a, M.; Garc\u0026iacute;a-Arroyo, F.; Soto, V.; Cruz-Robles, D.; Nakagawa, T.; Yu, M.A.; Kang, D.-H.; Johnson, R.J. Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations. \u003cem\u003eNephron Experimental Nephrology \u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e121\u003c/em\u003e, e71-e78.\u003c/li\u003e\n\u003cli\u003eZoccali, C.; Maio, R.; Mallamaci, F.; Sesti, G.; Perticone, F. Uric acid and endothelial dysfunction in essential hypertension. \u003cem\u003eJournal of the American Society of Nephrology \u003c/em\u003e\u003cstrong\u003e2006\u003c/strong\u003e, \u003cem\u003e17\u003c/em\u003e, 1466-1471.\u003c/li\u003e\n\u003cli\u003eMazzali, M.; Hughes, J.; Kim, Y.-G.; Jefferson, J.A.; Kang, D.-H.; Gordon, K.L.; Lan, H.Y.; Kivlighn, S.; Johnson, R.J. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. \u003cem\u003ehypertension \u003c/em\u003e\u003cstrong\u003e2001\u003c/strong\u003e, \u003cem\u003e38\u003c/em\u003e, 1101-1106.\u003c/li\u003e\n\u003cli\u003eRabadi, M.M.; Kuo, M.-C.; Ghaly, T.; Rabadi, S.M.; Weber, M.; Goligorsky, M.S.; Ratliff, B.B. Interaction between uric acid and HMGB1 translocation and release from endothelial cells. \u003cem\u003eAmerican Journal of Physiology-Renal Physiology \u003c/em\u003e\u003cstrong\u003e2012\u003c/strong\u003e, \u003cem\u003e302\u003c/em\u003e, F730-F741.\u003c/li\u003e\n\u003cli\u003eCorry, D.B.; Eslami, P.; Yamamoto, K.; Nyby, M.D.; Makino, H.; Tuck, M.L. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin\u0026ndash;angiotensin system. \u003cem\u003eJournal of hypertension \u003c/em\u003e\u003cstrong\u003e2008\u003c/strong\u003e, \u003cem\u003e26\u003c/em\u003e, 269-275.\u003c/li\u003e\n\u003cli\u003eAli, N.; Rahman, S.; Islam, S.; Haque, T.; Molla, N.H.; Sumon, A.H.; Kathak, R.R.; Asaduzzaman, M.; Islam, F.; Mohanto, N.C. The relationship between serum uric acid and lipid profile in Bangladeshi adults. \u003cem\u003eBMC cardiovascular disorders \u003c/em\u003e\u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e19\u003c/em\u003e, 1-7.\u003c/li\u003e\n\u003cli\u003eKhosla, U.M.; Zharikov, S.; Finch, J.L.; Nakagawa, T.; Roncal, C.; Mu, W.; Krotova, K.; Block, E.R.; Prabhakar, S.; Johnson, R.J. Hyperuricemia induces endothelial dysfunction. \u003cem\u003eKidney Int \u003c/em\u003e\u003cstrong\u003e2005\u003c/strong\u003e, \u003cem\u003e67\u003c/em\u003e, 1739-1742, doi:10.1111/j.1523-1755.2005.00273.x.\u003c/li\u003e\n\u003cli\u003eGinsberg, M.; Kozin, F.; O\u0026apos;malley, M.; McCarty, D. Release of platelet constituents by monosodium urate crystals. \u003cem\u003eThe Journal of clinical investigation \u003c/em\u003e\u003cstrong\u003e1977\u003c/strong\u003e, \u003cem\u003e60\u003c/em\u003e, 999-1007.\u003c/li\u003e\n\u003cli\u003eShashar, M.; Francis, J.; Chitalia, V. Thrombosis in the uremic milieu--emerging role of \u0026quot;thrombolome\u0026quot;. \u003cem\u003eSemin Dial \u003c/em\u003e\u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e28\u003c/em\u003e, 198-205, doi:10.1111/sdi.12255.\u003c/li\u003e\n\u003cli\u003eOfori, S.N.; Odia, O.J. Serum uric acid and target organ damage in essential hypertension. \u003cem\u003eVasc Health Risk Manag \u003c/em\u003e\u003cstrong\u003e2014\u003c/strong\u003e, \u003cem\u003e10\u003c/em\u003e, 253-261, doi:10.2147/vhrm.S61363.\u003c/li\u003e\n\u003cli\u003eLee, S.W.; Yang, Y.M.; Kim, H.Y.; Cho, H.; Nam, S.W.; Kim, S.M.; Kwon, S.K. Predialysis Urea Nitrogen Is a Nutritional Marker of Hemodialysis Patients. \u003cem\u003eChonnam Med J \u003c/em\u003e\u003cstrong\u003e2022\u003c/strong\u003e, \u003cem\u003e58\u003c/em\u003e, 69-74, doi:10.4068/cmj.2022.58.2.69.\u003c/li\u003e\n\u003cli\u003eLiu, Y.; Coresh, J.; Eustace, J.A.; Longenecker, J.C.; Jaar, B.; Fink, N.E.; Tracy, R.P.; Powe, N.R.; Klag, M.J. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. \u003cem\u003eJama \u003c/em\u003e\u003cstrong\u003e2004\u003c/strong\u003e, \u003cem\u003e291\u003c/em\u003e, 451-459, doi:10.1001/jama.291.4.451.\u003c/li\u003e\n\u003cli\u003eKovesdy, C.P.; Kopple, J.D.; Kalantar-Zadeh, K. Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy1234. \u003cem\u003eThe American Journal of Clinical Nutrition \u003c/em\u003e\u003cstrong\u003e2013\u003c/strong\u003e, \u003cem\u003e97\u003c/em\u003e, 1163-1177, doi:https://doi.org/10.3945/ajcn.112.036418.\u003c/li\u003e\n\u003cli\u003eDom\u0026iacute;nguez-Zambrano, E.; Pedraza-Chaverri, J.; L\u0026oacute;pez-Santos, A.L.; Medina-Campos, O.N.; Cruz-Rivera, C.; Bueno-Hern\u0026aacute;ndez, F.; Espinosa-Cuevas, A. Association between Serum Uric Acid Levels, Nutritional and Antioxidant Status in Patients on Hemodialysis. \u003cem\u003eNutrients \u003c/em\u003e\u003cstrong\u003e2020\u003c/strong\u003e, \u003cem\u003e12\u003c/em\u003e, doi:10.3390/nu12092600.\u003c/li\u003e\n\u003cli\u003eNieto, F.J.; Iribarren, C.; Gross, M.D.; Comstock, G.W.; Cutler, R.G. Uric acid and serum antioxidant capacity: a reaction to atherosclerosis? \u003cem\u003eAtherosclerosis \u003c/em\u003e\u003cstrong\u003e2000\u003c/strong\u003e, \u003cem\u003e148\u003c/em\u003e, 131-139.\u003c/li\u003e\n\u003cli\u003eKim, S.B.; Yang, W.S.; Min, W.K.; Lee, S.K.; Park, J.S. Reduced oxidative stress in hypoalbuminemic CAPD patients. \u003cem\u003ePeritoneal dialysis international \u003c/em\u003e\u003cstrong\u003e2000\u003c/strong\u003e, \u003cem\u003e20\u003c/em\u003e, 290-294.\u003c/li\u003e\n\u003cli\u003eMaxwell, S.R.J.; Thomason, H.; Sandler, D.; Leguen, C.; Baxter, M.; Thorpe, G.; Jones, A.; Barnett, A. Antioxidant status in patients with uncomplicated insulin‐dependent and non‐insulin‐dependent diabetes mellitus. \u003cem\u003eEuropean journal of clinical investigation \u003c/em\u003e\u003cstrong\u003e1997\u003c/strong\u003e, \u003cem\u003e27\u003c/em\u003e, 484-490.\u003c/li\u003e\n\u003cli\u003eTariq, M.A.; Shamim, S.A.; Rana, K.F.; Saeed, A.; Malik, B.H. Serum Uric Acid - Risk Factor for Acute Ischemic Stroke and Poor Outcomes. \u003cem\u003eCureus \u003c/em\u003e\u003cstrong\u003e2019\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e, e6007, doi:10.7759/cureus.6007.\u003c/li\u003e\n\u003cli\u003eHink, H.U.; Santanam, N.; Dikalov, S.; McCann, L.; Nguyen, A.D.; Parthasarathy, S.; Harrison, D.G.; Fukai, T. Peroxidase properties of extracellular superoxide dismutase: role of uric acid in modulating in vivo activity. \u003cem\u003eArteriosclerosis, thrombosis, and vascular biology \u003c/em\u003e\u003cstrong\u003e2002\u003c/strong\u003e, \u003cem\u003e22\u003c/em\u003e, 1402-1408.\u003c/li\u003e\n\u003cli\u003eSautin, Y.Y.; Johnson, R.J. Uric acid: the oxidant-antioxidant paradox. \u003cem\u003eNucleosides Nucleotides Nucleic Acids \u003c/em\u003e\u003cstrong\u003e2008\u003c/strong\u003e, \u003cem\u003e27\u003c/em\u003e, 608-619, doi:10.1080/15257770802138558.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4752853/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4752853/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eSerum uric acid (UA) level in end stage renal disease (ESRD) patients is an important physiological index for nutrition and inflammation. Serum UA displays a U-shape associated with all-cause mortality in ESRD patients. In this study, we evaluated relevance of serum UA level with survival rate in ESRD patients according to Charlson comorbidity index (CCI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eOur cohort of2615 subjects suffer from ESRD with CCI \u0026lt; 4 and ≥ 4. Of the 2615 subjects, 1107 subjects are CCI \u0026lt; 4 and others are CCI ≥ 4. The two independent groups were individually marked by serum UA sextiles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eWith Cox regression, serum UA levels higher than 8.6 mg/dl in the ESRD with CCI \u0026lt; 4 denoted as risk factor for all-cause mortality (hazard ratio (HR): 1.61, 95% CI: 1.01–2.38), compared to these subjects with UA of 7.1-7.7 mg/dl. In contrast, serum UA levels \u0026lt; 5.8 mg/dl represent risk factor for all-cause mortality in subjects with CCI ≥ 4 (HR: 1.53, 95% CI: 1.20–1.95) compared with UA \u0026gt; 8.6 mg/dl.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eHigher serum UA in ESRD subjects with high comorbidities is hardly a risk factor. Profoundly, low UA should be prevented in all ESRD patients.\u003c/p\u003e","manuscriptTitle":"Serum Uric acid level as an estimated parameter predicts all-cause mortality in patients with hemodialysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 01:01:11","doi":"10.21203/rs.3.rs-4752853/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cf849112-5ed5-46e0-8c96-748cfbdd0fb5","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":35760379,"name":"Health sciences/Nephrology/Renal replacement therapy"},{"id":35760380,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2024-10-25T05:54:32+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-17 01:01:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4752853","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4752853","identity":"rs-4752853","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}