Albuminuria Is Associated with Multidimensional Cardiorenal injury in Adults with Steady-State Sickle Cell Disease: A Multicenter Study with Measured GFR

Albuminuria Is Associated with Multidimensional Cardiorenal injury in Adults with Steady-State Sickle Cell Disease: A Multicenter Study with Measured GFR | 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 Research Article Albuminuria Is Associated with Multidimensional Cardiorenal injury in Adults with Steady-State Sickle Cell Disease: A Multicenter Study with Measured GFR Yannick Mompango Engole, Justine Busanga Bukabau, Yannick Mayamba Nlandu, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9058136/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Albuminuria is an early marker of glomerular injury in sickle cell disease (SCD) and predicts progressive renal impairment. Data on albuminuria among adults with SCD in sub-Saharan Africa remain limited. This study aimed to determine the prevalence of albuminuria and identify associated factors in adults with steady-state SCD in Kinshasa, Democratic Republic of Congo. Methods We conducted a multicenter cross-sectional study including 279 adults (≥ 18 years) with steady-state SCD. Albuminuria was assessed using the urinary albumin-to-creatinine ratio (UACR) and categorized according to KDIGO criteria. Glomerular filtration rate (GFR) was measured by plasma iohexol clearance. Cardiac function was evaluated by Doppler echocardiography, and arterial stiffness was assessed using pulse wave velocity (PWV). Multivariate linear and logistic regression analyses were performed to identify independent determinants of albuminuria. Results The overall prevalence of albuminuria was 29.1%, including 21.5% grade A2 and 7.5% grade A3. Albuminuria was associated with elevated systolic blood pressure (SBP), lactate dehydrogenase (LDH), PWV, increased cardiac output, and reduced systemic vascular resistance (SVR). In multivariate analysis, urinary α-1 microglobulin ≥ 12 mg/L (aOR 3.01, 95% CI 1.80–4.02), recent vaso-occlusive crisis (aOR 2.71, 95% CI 1.22–4.21), LDH > 246 IU/L (aOR 3.57, 95% CI 2.40–6.13), and SVR < 700 dyn·s/cm⁵ (aOR 1.91, 95% CI 1.51–7.15) remained independently associated with albuminuria. Conclusions Nearly one-third of adults with steady-state SCD had albuminuria. Hemolysis, tubular injury, recent vaso-occlusive events, and vascular dysfunction were key determinants, highlighting the interplay between glomerular hyperfiltration and systemic vasculopathy. Longitudinal studies are warranted to assess persistence and progression of renal involvement. Albuminuria α-1 microglobulin steady-state sickle cell disease adults hemolysis vascular resistance Figures Figure 1 Figure 2 Introduction Sickle cell disease (SCD) is a multisystem genetic disorder that affects several organs, including the kidneys. Chronic kidney disease (CKD) related to SCD represents a major contributor to morbidity and is associated with a mortality rate of approximately 16–18% among affected individuals younger than 40 years [ 1 ]. Early identification of renal involvement is therefore essential to improve survival and quality of life in this population. Albuminuria is recognized as one of the earliest clinical markers of renal injury and reflects underlying pathophysiological and molecular alterations that precede overt renal dysfunction [ 2 ]. While albuminuria provides important clinical information, assessment of glomerular filtration rate (GFR) remains useful for characterizing renal functional status and contextualizing early renal injury in SCD. Renal involvement in SCD typically develops early and has traditionally been attributed to glomerulopathy associated with increased renal plasma flow and glomerular hyperfiltration. These hemodynamic changes promote glomerular hypertrophy and progressive sclerosis, ultimately leading to disruption of the glomerular filtration barrier, including podocytes, endothelial cells, and mesangial cells [ 3 ]. Several biological pathways contribute to this injury, including activation of the renin–angiotensin–aldosterone system (RAAS) and endothelin-1 signaling, both of which play key roles in the progression of glomerular damage [ 4 , 5 ]. However, growing evidence suggests that early renal injury in SCD also involves tubular dysfunction and systemic vascular alterations, indicating that albuminuria may reflect a broader spectrum of renal and cardiorenal injury. In this context, direct measurement of GFR may provide additional insight into renal functional changes that accompany albuminuria, particularly in SCD where estimation equations may be influenced by hyperfiltration, chronic anemia, and altered muscle mass. Hyperfiltration, frequently detected during childhood in patients with SCD [ 6 ], may persist into adulthood and contribute to the development of albuminuria [ 7 ]. In addition, chronic intravascular hemolysis, a central feature of SCD, contributes to renal injury through the release of cell-free hemoglobin and heme, leading to nitric oxide depletion, oxidative stress, inflammation, and microvascular dysfunction affecting both glomerular and tubular compartments [ 8 , 9 ]. Clinically, albuminuria is of particular importance because it is strongly associated with subsequent decline in glomerular filtration rate (GFR), highlighting the need for early detection and timely intervention. Measurement of GFR may therefore complement albuminuria evaluation by providing a more comprehensive characterization of renal involvement in SCD [ 10 ]. The reported prevalence of albuminuria among individuals with SCD varies widely across populations, ranging from 15% to 50% globally [ 11 ]. In sub-Saharan Africa, prevalence estimates are approximately 27% [ 12 ], while studies conducted among children in the Democratic Republic of Congo (DRC) have reported prevalence rates of 18.5% [ 7 ]. Notably, a study conducted in eastern DRC across all age groups reported a remarkably high microalbuminuria prevalence of 86.7% [ 13 ], underscoring the potential magnitude of renal involvement in this region. We hypothesized that albuminuria in adults with SCD reflects a multifactorial renal injury driven by the interaction between chronic hemolysis, tubular dysfunction, and systemic vascular alterations rather than isolated glomerular damage. Therefore, this study aimed to determine the prevalence of albuminuria and identify associated factors among adults with SCD in a steady-state condition in Kinshasa. Materials and Methods Study Design and Population This was a multicentre, analytical, cross-sectional study conducted between March and December 2023 in Kinshasa, Democratic Republic of the Congo. Adult patients with steady-state SCD were recruited from 13 healthcare centres: the Centre for Mixed Medicine and SS Anemia, Makala General Reference Hospital, Bonkoko Medical Center, Akram Hospital, Messie Center, Elisabeth Clinic, Amza Foundation, Rezodrepa, Codek, Colombe, Kintambo Hospital, Salvation Center, and Lisungi. Ethical approval was obtained from the Ethics Committee of the School of Public Health at the University of Kinshasa (Approval No. ESP/CE/143/2022). All examinations and methods were performed after obtaining written informed consent from the patients and an explanation in accordance with the Helsinki guidelines. Inclusion and Exclusion Criteria Eligible participants were adults (≥ 18 years old) with SCD in a steady-state condition. Patients with HIV infection, hepatitis B or C, or diabetes mellitus were excluded from the study. Biological Assessments Albuminuria was quantified using the urinary albumin-to-creatinine ratio (UACR, mg/g), calculated as the ratio of urinary albumin (mg/L) to urinary creatinine (mg/L), measured by immunonephelometry (Roche Diagnostics, Mannheim, Germany). Prior to this, urinalysis was performed using a standard 10-parameter dipstick test. Urinary α-1 microglobulin was assessed using the same method. Other biological parameters were measured using standard hospital laboratory techniques. Serum creatinine and cystatin C levels were determined enzymatically and by immunoturbidimetry, respectively, using a Roche Cobas analyzer. Complete blood counts were conducted via impedance analysis with a Zybio analyzer (Seoul, South Korea). Lactate dehydrogenase (LDH), aspartate transaminase (GOT), and bilirubin (total and direct) were measured by kinetic enzymatic methods using a semi-automated platform. Fetal hemoglobin (HbF) and hemoglobin S (HbS) levels were quantified by cellulose acetate electrophoresis using a Gazelle analyzer (Hemex Health, Portland, USA). Renal Function Assessment Glomerular filtration rate (GFR) was measured by plasma clearance of iohexol (Omnipaque, 350 mg I/mL, GE Healthcare, Belgium), with each patient receiving a 5 mL injection. Five blood samples were collected from the contralateral arm at 60, 120, 180, 240 and 300 minutes post-injection [ 14 ]. Samples were stored at − 80°C and later analyzed at the University of Liège (Belgium) using liquid chromatography–tandem mass spectrometry (LC-MS/MS) [ 15 ]. Cardiac Evaluation Transthoracic Doppler echocardiography was performed by a single experienced cardiologist using a Mindray Z60 ultrasound machine (Shenzhen, China), following international guidelines [ 16 ]. Measurements in diastole included the left ventricular end-diastolic diameter, interventricular septum thickness, and posterior wall thickness. Left ventricular mass (LVM) was calculated and indexed to body surface area (BSA) [ 17 ]. The ejection fraction was calculated using Simpson’s modified biplane method, and the left atrial volume was indexed to BSA. Transmitral flow parameters (E/A ratio, E/E’) and left ventricular outflow velocity-time integral were obtained via Doppler. Cardiac output and cardiac index (CI) were also calculated. Pulmonary hypertension was defined as a tricuspid regurgitant jet velocity > 2.5 m/s [ 18 ]. Systemic vascular resistance (SVR) was considered low when < 700 dynes·s/cm⁵, and was calculated using the formula: SVR = 80 × mean arterial pressure / CI [ 9 ]. Vascular Stiffness Measurement Aortic stiffness was assessed via carotid-to-femoral pulse wave velocity (PWV), measured by foot-to-foot method using the Popmeter device (Axelfil, France) [ 19 ]. PWV was calculated by dividing the distance between the recording sites by the pulse transit time. Additional vascular parameters recorded included central systolic pressure (CSP), central diastolic pressure (CDP), pulse pressure, and heart rate. Operational definitions Steady-state SCD: Absence of a history of vaso-occlusive crisis (VOC) or within 1 month of infection, hospitalization for acute chest syndrome, fever in the last month, ongoing pregnancy, urinary tract infection, or use of aminoglycosides or non-steroidal anti-inflammatory drugs in the preceding month. Recent vaso-occlusive crises: history of vaso-occlusive crises in the previous trimester Adult: Age ≥ 18 years Albuminuria grade A1: UACR < 30 mg/g [ 20 ] Albuminuria grade A2: UACR: 30–300 mg/g, Albuminuria grade A3: UACR ≥ 300 mg/g Statistical Analysis All data were recorded using Microsoft Excel and analyzed with SPSS version 21. Descriptive statistics were used to summarize the characteristics of patients with and without albuminuria. Quantitative variables were expressed as mean ± standard deviation or as median with minimum and maximum values, while categorical variables were expressed as percentages. Comparisons between groups were performed using the unpaired t-test for continuous variables and the Chi-square test or Fisher’s exact test for categorical variables. A significance level (α) of 0.05 was considered for all comparisons. Multiple linear regression and multiple logistic regression analyses were used to identify independent determinants of albuminuria, with 95% confidence intervals (CIs) reported for each factor. The association between albuminuria and various clinical or biological parameters was also analyzed using Spearman’s correlation and the Kruskal-Wallis test to evaluate differences across albuminuria categories. Adjustments were made for SBP, LDH and PWV. A two-tailed p-value < 0.05 was considered statistically significant. Results A total of 279 patients with steady-state sickle cell disease (SCD) were included in the study. The median urinary albumin-to-creatinine ratio (UACR) for the study population was 6.6 mg/g (3.4–12.7) in grade A1, 79.1 mg/g (45.1–133.6) in grade A2, and 790.3 mg/g (412.2–1209.3) in grade A3 albuminuria. The overall prevalence of albuminuria was 29.1% (81/279). Table 1 summarizes patient characteristics by albuminuria category. Several clinical complications differed significantly across groups: history of vaso-occlusive crisis (VOC) in the previous trimester (79 [41.6%] vs 23 [38.3%] vs 16 [80.0%]; p = 0.003), leg ulceration (50 [26.2%] vs 15 [25.0%] vs 11 [55.0%]; p = 0.028), α-1-microglobulin positivity (105 [53.0%] vs 51 [85.0%] vs 20 [95.2%]; p < 0.001), and low systemic vascular resistance (SVR) (19 [22.1%] vs 4 [26.7%] vs 3 [30.0%]; p = 0.018). Table 1 General characteristics of patients studied according to albuminuria Variables Over all (n = 279) Albuminuria grade A1 (n = 198) Albuminuria grade A2 (n = 60) Albuminuria grade A3 (n = 21) p Sex 0.498 Female 167(59.9) 120(60.6) 37(61.7) 10(47.6) Male 112(40.1) 78(39.4) 23(38.3) 11(52.4) Age 26.3 ± 8.4 26.2 ± 8.3 26.5 ± 8.1 26.6 ± 10.1 0.226 < 25 years 152(54.5) 112(56.6) 27(45.0) 13(61.9) ≥ 25 years 127(45.5) 86(43.4) 33(55.0) 8(38.1) Folic acid intake 255(94.4) 179(94.2) 57(95.0) 19(95.0) 0.514 Hydroxyurea use 101(37.4) 73(38.4) 19(31.7) 9(45.0) 0.479 Surgery 66(24.4) 51(26.8) 12(20.0) 3(15.0) 0.367 History of VOC (previous trimester) 118(43.7) 79(41.6) 23(38.3) 16(80.0) 0.003 Leg ulcer 76(28.0) 50(26.2) 15(25.0) 11(55.0) 0.028 Priapism 18(6.6) 12(6.3) 3(5.0) 3(15.0) 0.280 Retinopathy 43(15.9) 32(16.8) 8(13.3) 3(15.0) 0.826 Aseptic necrosis of femoral head 51(18.8) 36(18.8) 12(20.0) 3(15.0) 0.933 Stroke 4(1.5) 1(0.5) 3(5.0) 0(0.0) 0.062 Tabacco 24(8.9) 13(6.8) 9(15.0) 2(10.0) 0.273 Alcohol 64(23.6) 47(24.6) 12(20.0) 5(25.0) 0.811 α-1 microglobulin ≥ 12 mg/L 176(63.1) 105(53.0) 51(85.0) 20(95.2) < 0.001 CRP ≥ 6 mg/L 169(60.8) 117(59.4) 39(65.0) 13(61.9) 0.751 Morphology of LV 0.475 Normal 43(37.4) 32(37.2) 6(28.6) 5(62.5) Concentric remodeling 7(6.1) 5(5.8) 1(4.8) 1(12.5) Concentric LVH 15(13.0) 13(15.1) 2(9.5) 0(0.0) Eccentric LVH 50(43.5) 36(41.9) 12(57.1) 2(25.0) Low SVR (< 700) 26(23.4) 19(22.1) 4(26.7) 3(30.0) 0.018 Normal Kidney 91(82.7) 62(79.5) 20(87.0) 9(100.0) 0.314 Nephromegaly 17(15.5) 14(17.9) 3(13.0) 0(0.0) 0.420 Data are expressed as mean ± standard deviation, absolute (n) and relative (in percent) frequencies. Abbreviations: Low SVR: Low Systemic vascular resistance; LVH: Left ventricular hypertrophy; LV Morphology: Left ventricular Morphology; Cystatin-C did not differ significantly between groups (0.84 [0.72–0.93] vs 0.86 [0.74–1.06] vs 0.91 [0.72–1.11] mg/L; p = 0.120). By contrast, LDH varied significantly (211.2 [195.5–264.4] vs 200.6 [184.5–253.0] vs 238.0 [200.0–402.6] IU/L; p = 0.016), as did systolic blood pressure (105.0 ± 13.6 vs 102.6 ± 10.8 vs 111.8 ± 14.6 mmHg; p = 0.031). GOT and reticulocyte counts were similar across groups, as were total and direct bilirubin and CRP. Although PWV tended to be lowest in grade A3, a significant overall difference was observed ( p = 0.017). TAPSE, while within the normal range, also differed (2.8 ± 0.4 vs 2.5 ± 0.4 vs 2.4 ± 0.4 cm; p = 0.040). Cardiac output did not vary significantly, but SVR was lower in grade A3 than in the other groups (Table 2 ). Table 2 Biological, hemodynamic and echocardiographic characteristics of the population studied according to Albuminuria Variables Total Albuminuria grade A1 Albuminuria grade A2 Albuminuria grade A3 p SBP, mmHg 106.0 ± 13.3 105.0 ± 13.6 102.6 ± 10.8 111.8 ± 14.6 0.031 DBP, mmHg 59.0 ± 9.8 59.3 ± 9.9 57.4 ± 8.2 60.8 ± 13.5 0.304 BSA, m 2 1.51(1.42–1.61) 1.51(1.42–1.60) 1.48(1.38–1.64) 1.53(1.44–1.61) 0.860 PWV, m/sec 5.4 ± 2.1 5.2 ± 1.1 5.1 ± 0.9 7.4 ± 5.9 0.010 ABI 1.09 ± 0.1 1.1 ± 0.1 1.1 ± 0.06 1.05 ± 0.07 0.450 IVSd, mm 8.7 ± 1.6 8.8 ± 1.6 8.4 ± 1.6 9.0 ± 1.3 0.566 PWd, mm 9.0 ± 1.6 9.1 ± 1.7 8.9 ± 1.5 8.8 ± 1.4 0.856 LVEF, % 68.0 ± 9.7 68.4 ± 10.0 66.1 ± 8.0 68.1 ± 10.2 0.610 LVEDD, mm 50.4 ± 5.5 50.0 ± 5.6 52.4 ± 5.2 49.0 ± 5.3 0.155 RVEDD, mm 28.2 ± 4.9 27.8 ± 5.1 29.5 ± 3.3 29.0 ± 5.8 0.328 iLVM, g/m 2 108.1 ± 26.2 108.7 ± 27.6 106.4 ± 19.1 106.5 ± 29.8 0.927 IVC, mm 12.6 ± 3.1 12.5 ± 3.2 12.8 ± 2.9 13.7 ± 3.1 0.513 E/E' 7.9 ± 1.9 7.8 ± 1.9 8.1 ± 1.6 8.4 ± 2.9 0.588 TRV, m/sec 1.67 ± 0.32 1.66 ± 0.31 1.77 ± 0.33 1.57 ± 0.33 0.150 TAPSE, cm 2.7 ± 0.4 2.8 ± 0.4 2.5 ± 0.4 2.4 ± 0.4 0.040 Cardiac output, l/min 6.71(5.33–8.45) 6.68(5.33–8.32) 7.86(5.75–8.80) 6.03(4.91–7.34) 0.395 SVR, dynes sec/cm 5 832.5(678.9-1089.9) 992.0(695.1-1141.6) 825.6(669.0-1093.5) 772.6(699.1-1040.1) 0.218 α-1 microglobulin, mg/L 20.1(7.9–40.9) 12.7(6.3–30.8) 29.2(16.1–57.4) 79.7(29.3–127.0) < 0.001 ACR, mg/G 11.2(4.2–41.5) 6.6(3.4–12.7) 79.1(45.1-133.6) 790.3(412.2-1209.3) < 0.001 Creatinine, mg/dL 0.6(0.5–0.7) 0.6(0.5–0.7) 0.6(0.5–0.8) 0.60(0.47–0.74) 0.892 Cystatine, mg/L 0.85(0.73–0.97) 0.84(0.72–0.93) 0.86(0.74–1.06) 0.91(0.72–1.11) 0.120 Measured GFR, mL/min/1.73m 2 128.0(105.0-150.5) 127.0(108.0-151.0) 128.0(94.0-155.8) 135.0(99.3-147.8) 0.747 Urea, mmol/L 4.81(3.5-6.0) 4.86(3.70–6.10) 4.94(3.32–5.97) 4.55(3.24–6.35) 0.785 RBC x 10 6 , /mm 3 2.6(2.3–3.1) 2.6(2.2–3.1) 2.68(2.26–3.20) 2.89(2.33–3.50) 0.366 Hb, g/dL 7.5 ± 1.8 7.4 ± 1.7 7.6 ± 1.5 7.9 ± 2.6 0.427 Hct, % 23.4 ± 5.8 23.3 ± 5.6 23.5 ± 5.0 24.9 ± 8.4 0.444 Reticulocytes, % 16.0(15.0–18.0) 16.0(15.0–18.0) 16.0(15.0–18.0) 16.0(14.0-17.5) 0.155 WBC x 10 3 , /mm 3 10.7(8.8–13.9) 11.1(8.9–14.2) 10.5(8.5–13.2) 10.1(8.2–14.2) 0.374 Platelets x 10 3 , /mm 3 156.3(150.6-163.2) 156.2(150.4-162.5) 156.9(151.1-164.9) 161.2(150.5-171.1) 0.407 GOT, IU/L 33.9(27.0-45.2) 33.3(27.0-44.6) 36.0(26.9–50.3) 32.3(27.3–47.5) 0.604 Total Bili, mg/L 1.0(0.9–1.2) 1.0(0.92–1.20) 1.00(0.92–1.29) 1.09(0.88–1.10) 0.721 Direct Bili, mg/L 0.30(0.24–0.52) 0.30(0.24–0.51) 0.31(0.25–0.68) 0.25(0.24–0.43) 0.447 LDH, IU/L 210.3(193.2-265.1) 211.2(195.0-260.4) 200.6(184.5–253.0) 238.0(200.0-402.6) 0.016 Ferritin, ng/mL 267.1(97.9-663.7) 247.4(95.7-600.2) 319.0(102.2–761.0) 276.1(171.5-569.4) 0.539 CRP, mg/L 8.5(3.3–20.3) 8.1(3.2–18.8) 9.5(4.4–24.7) 10.0(2.5–15.3) 0.582 Fetal Hb, % 9.0(8.0–13.0) 9.0(8.0–13.0) 10.0(8.0–16.0) 9.0(6.8–11.8) 0.170 Data are expressed as mean ± standard deviation, median (interquartile range), absolute (n) and relative (in percent) frequencies. Abbreviations: ABI: Ankle brachial index; ACR: Albuminuria-creatinine ratio; BSA: Body surface area; CRP: C-reactive protein; DBP: Diastolic blood pressure; GOT: glutamooxaloacetate transferase; Hb: Haemoglobin; Hct: Haematocrit; IVC: Inferior vena cava; LDH: Lactate dehydrogenase; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; SBP: Systolic blood pressure; LVMi : Indexed left ventricular mass; PW: Posterior wall; PWV: Pulse wave velocity; RBC: Red blood cells; TAPSE: Tricuspid annular plane systolic excursion; TRV: Tricuspid regurgitation time; SBP: Systolic blood pressure; SVR: Systemic vascular resistance; WBC: White blood cells. LDH, SBP, and PWV were markedly higher in grade A3 than in grades A1 or A2 ( p = 0.010, 0.031, and 0.010, respectively; Fig. 1 ). Multiple linear regression (Table 3 ) showed albuminuria was independently associated with SBP (β = 2.56; p = 0.012), LDH (β = 1.373; p = 0.012), PWV (β = 3.279; p = 0.037), cardiac output (β = 1.262; p = 0.029), and SVR (β = -0.081; p = 0.021), explaining 56.3% of the variance (R² = 0.563). Table 3 Associated factors of albuminuria in the population studied (Multiple linear regression) Variable ꞵ ES p CI 95% (Constante) -2.776 32.994 0.646 (-67.3 ; 33.7) SBP, mmHg 2.560 6.746 0.012 (2.3 ; 17.4) BMI, Kg/m 2 -6.328 31.162 0.843 (-74.9 ; 62.3) Urinary α-1 microglobulin, mg/L 0.450 0.868 0.614 (-1.25 ; 2.15) WBC, /mm 3 -4.753 11.934 0.698 (-28.1 ; 18.6) LDH, IU/L 1.373 0.827 0.012 (0.45 ; 3.19) PWV, m/sec 3.279 6.955 0.037 (0.87 ; 12.28) TAPSE, cm 5.107 16.018 0.756 (-26.3 ; 36.5) Cardiac output, L/min 1.262 4.628 0.029 (0.25 ; 11.35) SVR, dyn.s/cm 5 -0.081 0.391 0.021 (-0.79 ; − 0.01) R 2 = 0.563 Abbreviations. SBP: Systolic blood pressure; BMI: Body mass index; WBC: White blood cell; LDH: Lactate dehydrogenase; PWV: Pulse wave velocity, SVR: Systemic vascular resistance In univariate logistic regression, α-1-microglobulin ≥ 12 mg/L, recent VOC, leg ulcers, LDH > 246 IU/L, and SVR < 700 dyn·s/cm⁵ were each associated with albuminuria ( p < 0.05). After multivariate adjustment, four factors remained significant: α-1-microglobulin ≥ 12 mg/L (aOR = 3.01, 95% CI 1.80–4.02; p = 0.016), recent VOC (aOR = 2.71, 95% CI 1.22–4.21; p = 0.024), LDH > 246 IU/L (aOR = 3.57, 95% CI 2.40–6.13; p = 0.014), and SVR < 700 dyn·s/cm⁵ (aOR = 1.91, 95% CI 1.51–7.15; p = 0.034) (Table 4 ). Table 4 Associated factors of albuminuria in the population studied (Logistic regression) Variable Univariate analysis Multivariate analysis p aOR (CI 95%) p aOR (CI 95%) Urinary α-1 microglobuline, mg/L < 12 1 1 ≥ 12 < 0.001 3.02(2.09–4.02) 0.016 3.01(1.80–4.02) History of VOC (previous trimester) No 1 1 Yes 0.028 3.38(1.79–5.26) 0.024 2.71(1.22–4.21) Leg ulcer No 1 1 Yes 0.029 2.36(1.77–3.40) 0.629 1.36(0.39–4.70) LDH > 246 IU/L No 1 1 Yes 0.017 2.91(1.59–3.84) 0.014 3.57(2.40–6.13) SVR < 700 dyn.s/cm 5 No 1 1 Yes 0.032 3.37(1.50–3.77) 0.034 1.91(1.51–7.15) Abbreviations. LDH: Lactate dehydrogenase; PWV: Pulse wave velocity, SVR: Systemic vascular resistance; VOC: Vaso-occlusive crise Discussion This study reported a 29.1% prevalence of albuminuria among adults with sickle cell disease (SCD), including 21.5% with grade A2 and 7.5% with grade A3 albuminuria. Albuminuria was independently associated with systolic blood pressure (SBP), lactate dehydrogenase (LDH), pulse wave velocity (PWV), increased cardiac output, reduced systemic vascular resistance (SVR), urinary α-1 microglobulin, and recent vaso-occlusive crises (VOC). Taken together, these findings support the concept that albuminuria in SCD reflects a multifactorial cardiorenal injury resulting from the interaction between hemolysis, tubular dysfunction, and systemic vascular alterations rather than isolated glomerular damage. The prevalence of albuminuria observed in our adult cohort was higher than that reported among Congolese children by Aloni et al. (18%) [ 7 ] and was comparable to estimates from McPherson et al. (20.7%) [ 21 ] and Ataga et al. (26%) [ 3 ]. However, it remained lower than prevalences reported by Kambale-Kombi et al. (86.7%) [ 13 ], Laurin et al. (45%) [ 22 ], and Drawz et al. (64%) [ 23 ]. These variations likely reflect differences in age distribution, study design, and therapeutic exposure, particularly the use of RAAS inhibitors, hydroxyurea, and statins [ 22 , 24 , 25 ]. Persistent albuminuria has been reported to occur more frequently in patients with higher baseline albuminuria or delayed initiation of hydroxyurea therapy, particularly after childhood [ 27 ]. The median albuminuria levels observed in our cohort were comparable to those reported by Drawz et al. [ 23 ] but lower than those described by Ataga et al. [ 5 ]. The pathophysiology of renal injury in SCD is complex and involves multiple interacting mechanisms including hyperfiltration, oxidative stress, and chronic intravascular hemolysis [ 5 , 28 ]. Hyperfiltration, a hallmark of early sickle nephropathy, has been reported in both pediatric and adult populations [ 7 , 29 ] and has been associated with progressive glomerular remodeling and albumin leakage [ 2 ]. In our study, elevated SBP was significantly associated with albuminuria. Increased renal plasma flow in SCD, often driven by elevated cardiac output and reduced SVR, may increase glomerular perfusion pressure and contribute to glomerular stress [ 30 – 32 ]. Similar observations were reported by Gosmanova et al., who identified SBP as a predictor of CKD progression in SCD populations [ 11 ]. These findings support the concept that systemic hemodynamic alterations contribute to renal injury. Chronic intravascular hemolysis represents another major contributor to renal damage. Reduced nitric oxide bioavailability, increased endothelin-1 activity, oxidative stress, and endothelial dysfunction have been described in SCD and have been associated with microvascular injury and albuminuria [ 5 , 8 , 23 , 33 , 34 ]. The higher prevalence of leg ulcers among patients with grade A3 albuminuria in our cohort further supports the link between systemic vasculopathy and renal involvement. LDH, a surrogate marker of intravascular hemolysis, was significantly associated with albuminuria severity. Chronic hemolysis has been linked to hyperfiltration and glomerular hypertrophy through heme-mediated vascular and inflammatory pathways [ 8 , 29 ]. In addition, chronic anemia may increase cardiac output and contribute to glomerular hemodynamic stress, which may explain the association between elevated cardiac output and albuminuria observed in our study. Previous studies have also shown that hydroxyurea therapy may reduce hyperfiltration and albuminuria, further supporting the role of hemolysis in renal injury [ 35 , 36 ]. Tubular dysfunction also appears to play a central role in SCD-related renal injury. Urinary α-1 microglobulin, a marker of proximal tubular injury, was independently associated with albuminuria, consistent with findings reported by Elsherif et al. [ 37 ]. Tubular injury in SCD has been attributed to recurrent ischemia-reperfusion injury during VOC episodes and oxidative stress. Histopathological studies demonstrating hemosiderin deposition in proximal tubular cells further support the relationship between hemolysis and tubular injury [ 38 ]. These findings suggest that albuminuria in SCD may partly reflect tubular-glomerular crosstalk rather than isolated glomerular pathology. Although CRP was not independently associated with albuminuria in our cohort, inflammation remains an important component of SCD pathophysiology. Hemolysis-related oxidative stress and inflammatory cytokine release, including TNF-α and IL-1β, have been implicated in endothelial activation and chronic renal injury [ 39 ]. Vascular dysfunction further contributes to renal vulnerability in SCD. Increased PWV, reflecting arterial stiffness, was associated with albuminuria, consistent with findings reported by Ranque et al. [ 40 ]. PWV reflects structural and functional alterations in medium and small arteries that may predispose to renal microvascular injury [ 41 ]. Reduced SVR, commonly observed in SCD due to nitric oxide-mediated vasodilation, has also been associated with increased renal plasma flow and filtration stress [ 9 , 42 ]. Taken together, these findings support an integrated cardiorenal model of renal injury in sickle cell disease. As illustrated in Fig. 2 , chronic intravascular hemolysis promotes nitric oxide depletion, oxidative stress, and inflammation, leading to systemic vascular dysfunction characterized by reduced systemic vascular resistance, increased cardiac output, and arterial stiffness. These hemodynamic alterations promote glomerular hyperfiltration and renal stress. Concurrently, recurrent vaso-occlusive events and hemolysis-related injury contribute to tubular dysfunction, reflected by increased urinary α-1 microglobulin. The combined effects of vascular dysfunction, glomerular stress, and tubular injury ultimately lead to albuminuria, which may represent an integrated marker of systemic vascular and renal injury rather than an isolated glomerular abnormality. This study has several limitations. The absence of additional markers of hemolysis and oxidative stress, such as haptoglobin, limited characterization of hemolytic burden. Albuminuria was assessed at a single time point, precluding evaluation of persistence. Nevertheless, this study represents the first investigation in the Democratic Republic of Congo combining direct measurement of glomerular filtration rate using iohexol clearance with albuminuria assessment and vascular evaluation using PWV, parameters recognized as valuable tools for early detection of renal dysfunction in recent SCD-specific recommendations [ 10 ]. Clinical Implications The present findings have several important clinical implications for the management of adults with sickle cell disease. First, the high prevalence of albuminuria observed in this study supports systematic screening for renal involvement even in patients in steady-state condition. Second, the strong association between albuminuria and markers of tubular injury, hemolysis, and vascular dysfunction suggests that renal risk assessment in sickle cell disease should not rely solely on glomerular markers but rather adopt an integrated cardiorenal approach. The identification of urinary α-1 microglobulin as an independent determinant of albuminuria highlights the potential value of tubular biomarkers for early detection of renal injury and improved risk stratification. In addition, the association between albuminuria and systemic hemodynamic alterations, including increased arterial stiffness and reduced systemic vascular resistance, underscores the need for multidisciplinary monitoring incorporating cardiovascular evaluation. Early identification of patients at higher renal risk may allow timely implementation of therapeutic strategies, including optimization of hydroxyurea therapy, blood pressure control, and potential use of renin–angiotensin–aldosterone system inhibitors. Finally, these findings support the need for longitudinal studies to determine whether combined biomarker-based screening strategies can improve renal outcomes in adults with sickle cell disease. Conclusion In adults with sickle cell disease, albuminuria is common and appears to reflect a multidimensional renal vulnerability driven by the interaction between chronic hemolysis, tubular injury, and systemic vascular dysfunction. These findings support the need for integrated renal risk assessment strategies beyond isolated glomerular markers. Longitudinal studies incorporating repeated albuminuria measurements and multimodal renal biomarkers are required to clarify the prognostic significance and therapeutic implications of albuminuria in this population. Declarations Acknowledgements The authors wish to thank the various medical centres and their coordinators for collecting data, particularly Dr. Grace Ngoy and Mrs. Ledya, as well as the team of nurses and laboratory technicians from the specialized clinics of Kinshasa. We also extend our sincere appreciation to Professors Pierre Delanaye, Etienne Cavalier, and the entire Sart Tilman Laboratory team at the University Hospital of Liège for their invaluable support. Consent statement All participants were provided informed consent during the study accordance with the Helsinki guidelines. Authors’ information Not applicable. Consent for publication Not applicable. Disclosure statement The authors report there are no competing interests to declare. Author contributions All authors of the manuscript participated in the realization and preparation of the study. YE, JB, JRM, and ES designed the study; acquired, analyzed, and interpreted the data; and drafted and revised the manuscript. AN performed statistical analysis and interpreted the data. BM performed the echocardiograms. DL performed renal ultrasounds. YN, MFM, BM, VM, FK, EK, BN, JM, AN and ES revised the manuscript. All authors (s) read and approved the final manuscript. Funding details This work was partly supported by the SFNDT (French Speaking Society of Nephrology, Dialysis, and Transplantation) Data availability statement The data can be made available via email to anyone who wishes to contact Yannick Engole at the following address: [email protected] References Hamideh D, Alvarez O. 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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-9058136","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616009433,"identity":"b777a4e0-a05f-489a-98d4-8949644ba820","order_by":0,"name":"Yannick Mompango Engole","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIiWNgGAWjYLCCBCAEAsYDDBUMDAYgZgWRWhgOMJyBajlDjD1gLYxtRGgxOH722IMHNWly5vyLDxz4OO+wvDl78wGGg3vwaDmTl26QcCzH2HLGs4SDM7cdNtzZcyyB4cAzPFoO5JhJJDZUJG64ccbgMO+2w4wbbuQYMH84gEfL+TdgLfVgLX/nHLYHaWE4gE/LDbAtOQkG53sMDjM2HE4kqEXyBtCWhGNphhtusCUc7DmWnrzhzLGEA/i08J3PMZP8UZMsb3D+8MEHP2qsbTccbz74AJ8WBbicRAKIbAaz8WhgYJBvgLH4werq8CkeBaNgFIyCEQoAlSZni6wCqR4AAAAASUVORK5CYII=","orcid":"","institution":"1. 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University of Kinshasa","correspondingAuthor":false,"prefix":"","firstName":"Ernest","middleName":"Kiswaya","lastName":"Sumaili","suffix":""}],"badges":[],"createdAt":"2026-03-07 11:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9058136/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9058136/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106000026,"identity":"c3af9a6a-20fa-4799-b57a-6c7e0b869958","added_by":"auto","created_at":"2026-04-02 09:52:07","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57944,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation between albuminuria and markers of vascular dysfunction and hemolysis in adults with sickle cell disease.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. Relationship between systolic blood pressure (SBP) and albumin-to-creatinine ratio (ACR).\u003cbr\u003e\nB. Relationship between lactate dehydrogenase (LDH) and albumin-to-creatinine ratio (ACR).\u003c/p\u003e\n\u003cp\u003eC. Relationship between pulse wave velocity (PWV) and albumin-to-creatinine ratio (ACR).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9058136/v1/da30e37ba45b62a1aed3a3b9.jpg"},{"id":106000025,"identity":"ce313caf-c7af-4cdf-9e2c-992038dd9453","added_by":"auto","created_at":"2026-04-02 09:52:07","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":121343,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConceptual cardiorenal pathway leading to albuminuria in adults with sickle cell disease\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9058136/v1/1151a36a951a97ffe9979546.jpg"},{"id":106093591,"identity":"18b1b572-babc-4787-baf8-9dcb7af0a064","added_by":"auto","created_at":"2026-04-03 11:38:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1545820,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9058136/v1/7e36d20f-06dd-49ec-bde2-e21fc6b6cc20.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAlbuminuria Is Associated with Multidimensional Cardiorenal injury in Adults with Steady-State Sickle Cell Disease: A Multicenter Study with Measured GFR\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSickle cell disease (SCD) is a multisystem genetic disorder that affects several organs, including the kidneys. Chronic kidney disease (CKD) related to SCD represents a major contributor to morbidity and is associated with a mortality rate of approximately 16\u0026ndash;18% among affected individuals younger than 40 years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Early identification of renal involvement is therefore essential to improve survival and quality of life in this population. Albuminuria is recognized as one of the earliest clinical markers of renal injury and reflects underlying pathophysiological and molecular alterations that precede overt renal dysfunction [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While albuminuria provides important clinical information, assessment of glomerular filtration rate (GFR) remains useful for characterizing renal functional status and contextualizing early renal injury in SCD.\u003c/p\u003e \u003cp\u003eRenal involvement in SCD typically develops early and has traditionally been attributed to glomerulopathy associated with increased renal plasma flow and glomerular hyperfiltration. These hemodynamic changes promote glomerular hypertrophy and progressive sclerosis, ultimately leading to disruption of the glomerular filtration barrier, including podocytes, endothelial cells, and mesangial cells [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Several biological pathways contribute to this injury, including activation of the renin\u0026ndash;angiotensin\u0026ndash;aldosterone system (RAAS) and endothelin-1 signaling, both of which play key roles in the progression of glomerular damage [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, growing evidence suggests that early renal injury in SCD also involves tubular dysfunction and systemic vascular alterations, indicating that albuminuria may reflect a broader spectrum of renal and cardiorenal injury. In this context, direct measurement of GFR may provide additional insight into renal functional changes that accompany albuminuria, particularly in SCD where estimation equations may be influenced by hyperfiltration, chronic anemia, and altered muscle mass.\u003c/p\u003e \u003cp\u003eHyperfiltration, frequently detected during childhood in patients with SCD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], may persist into adulthood and contribute to the development of albuminuria [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, chronic intravascular hemolysis, a central feature of SCD, contributes to renal injury through the release of cell-free hemoglobin and heme, leading to nitric oxide depletion, oxidative stress, inflammation, and microvascular dysfunction affecting both glomerular and tubular compartments [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Clinically, albuminuria is of particular importance because it is strongly associated with subsequent decline in glomerular filtration rate (GFR), highlighting the need for early detection and timely intervention. Measurement of GFR may therefore complement albuminuria evaluation by providing a more comprehensive characterization of renal involvement in SCD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe reported prevalence of albuminuria among individuals with SCD varies widely across populations, ranging from 15% to 50% globally [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In sub-Saharan Africa, prevalence estimates are approximately 27% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], while studies conducted among children in the Democratic Republic of Congo (DRC) have reported prevalence rates of 18.5% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Notably, a study conducted in eastern DRC across all age groups reported a remarkably high microalbuminuria prevalence of 86.7% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], underscoring the potential magnitude of renal involvement in this region.\u003c/p\u003e \u003cp\u003eWe hypothesized that albuminuria in adults with SCD reflects a multifactorial renal injury driven by the interaction between chronic hemolysis, tubular dysfunction, and systemic vascular alterations rather than isolated glomerular damage. Therefore, this study aimed to determine the prevalence of albuminuria and identify associated factors among adults with SCD in a steady-state condition in Kinshasa.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Population\u003c/h2\u003e \u003cp\u003eThis was a multicentre, analytical, cross-sectional study conducted between March and December 2023 in Kinshasa, Democratic Republic of the Congo. Adult patients with steady-state SCD were recruited from 13 healthcare centres: the Centre for Mixed Medicine and SS Anemia, Makala General Reference Hospital, Bonkoko Medical Center, Akram Hospital, Messie Center, Elisabeth Clinic, Amza Foundation, Rezodrepa, Codek, Colombe, Kintambo Hospital, Salvation Center, and Lisungi.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e was obtained from the Ethics Committee of the School of Public Health at the University of Kinshasa (Approval No. ESP/CE/143/2022). All examinations and methods were performed after obtaining written informed consent from the patients and an explanation in accordance with the Helsinki guidelines.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eInclusion and Exclusion Criteria\u003c/p\u003e \u003cp\u003eEligible participants were adults (\u0026ge;\u0026thinsp;18 years old) with SCD in a steady-state condition. Patients with HIV infection, hepatitis B or C, or diabetes mellitus were excluded from the study.\u003c/p\u003e \u003cp\u003eBiological Assessments\u003c/p\u003e \u003cp\u003eAlbuminuria was quantified using the urinary albumin-to-creatinine ratio (UACR, mg/g), calculated as the ratio of urinary albumin (mg/L) to urinary creatinine (mg/L), measured by immunonephelometry (Roche Diagnostics, Mannheim, Germany). Prior to this, urinalysis was performed using a standard 10-parameter dipstick test. Urinary α-1 microglobulin was assessed using the same method. Other biological parameters were measured using standard hospital laboratory techniques. Serum creatinine and cystatin C levels were determined enzymatically and by immunoturbidimetry, respectively, using a Roche Cobas analyzer. Complete blood counts were conducted via impedance analysis with a Zybio analyzer (Seoul, South Korea). Lactate dehydrogenase (LDH), aspartate transaminase (GOT), and bilirubin (total and direct) were measured by kinetic enzymatic methods using a semi-automated platform. Fetal hemoglobin (HbF) and hemoglobin S (HbS) levels were quantified by cellulose acetate electrophoresis using a Gazelle analyzer (Hemex Health, Portland, USA).\u003c/p\u003e \u003cp\u003eRenal Function Assessment\u003c/p\u003e \u003cp\u003eGlomerular filtration rate (GFR) was measured by plasma clearance of iohexol (Omnipaque, 350 mg I/mL, GE Healthcare, Belgium), with each patient receiving a 5 mL injection. Five blood samples were collected from the contralateral arm at 60, 120, 180, 240 and 300 minutes post-injection [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Samples were stored at \u0026minus;\u0026thinsp;80\u0026deg;C and later analyzed at the University of Li\u0026egrave;ge (Belgium) using liquid chromatography\u0026ndash;tandem mass spectrometry (LC-MS/MS) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCardiac Evaluation\u003c/p\u003e \u003cp\u003eTransthoracic Doppler echocardiography was performed by a single experienced cardiologist using a Mindray Z60 ultrasound machine (Shenzhen, China), following international guidelines [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Measurements in diastole included the left ventricular end-diastolic diameter, interventricular septum thickness, and posterior wall thickness. Left ventricular mass (LVM) was calculated and indexed to body surface area (BSA) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The ejection fraction was calculated using Simpson\u0026rsquo;s modified biplane method, and the left atrial volume was indexed to BSA. Transmitral flow parameters (E/A ratio, E/E\u0026rsquo;) and left ventricular outflow velocity-time integral were obtained via Doppler. Cardiac output and cardiac index (CI) were also calculated. Pulmonary hypertension was defined as a tricuspid regurgitant jet velocity\u0026thinsp;\u0026gt;\u0026thinsp;2.5 m/s [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Systemic vascular resistance (SVR) was considered low when \u0026lt;\u0026thinsp;700 dynes\u0026middot;s/cm⁵, and was calculated using the formula: SVR\u0026thinsp;=\u0026thinsp;80 \u0026times; mean arterial pressure / CI [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVascular Stiffness Measurement\u003c/p\u003e \u003cp\u003eAortic stiffness was assessed via carotid-to-femoral pulse wave velocity (PWV), measured by foot-to-foot method using the Popmeter device (Axelfil, France) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. PWV was calculated by dividing the distance between the recording sites by the pulse transit time. Additional vascular parameters recorded included central systolic pressure (CSP), central diastolic pressure (CDP), pulse pressure, and heart rate.\u003c/p\u003e \u003cp\u003e \u003cb\u003eOperational definitions\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSteady-state SCD: Absence of a history of vaso-occlusive crisis (VOC) or within 1 month of infection, hospitalization for acute chest syndrome, fever in the last month, ongoing pregnancy, urinary tract infection, or use of aminoglycosides or non-steroidal anti-inflammatory drugs in the preceding month.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRecent vaso-occlusive crises: history of vaso-occlusive crises in the previous trimester\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAdult: Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAlbuminuria grade A1: UACR\u0026thinsp;\u0026lt;\u0026thinsp;30 mg/g [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAlbuminuria grade A2: UACR: 30\u0026ndash;300 mg/g,\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAlbuminuria grade A3: UACR\u0026thinsp;\u0026ge;\u0026thinsp;300 mg/g\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll data were recorded using Microsoft Excel and analyzed with SPSS version 21. Descriptive statistics were used to summarize the characteristics of patients with and without albuminuria. Quantitative variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or as median with minimum and maximum values, while categorical variables were expressed as percentages. Comparisons between groups were performed using the unpaired t-test for continuous variables and the Chi-square test or Fisher\u0026rsquo;s exact test for categorical variables. A significance level (α) of 0.05 was considered for all comparisons. Multiple linear regression and multiple logistic regression analyses were used to identify independent determinants of albuminuria, with 95% confidence intervals (CIs) reported for each factor. The association between albuminuria and various clinical or biological parameters was also analyzed using Spearman\u0026rsquo;s correlation and the Kruskal-Wallis test to evaluate differences across albuminuria categories. Adjustments were made for SBP, LDH and PWV. A two-tailed p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 279 patients with steady-state sickle cell disease (SCD) were included in the study. The median urinary albumin-to-creatinine ratio (UACR) for the study population was 6.6 mg/g (3.4\u0026ndash;12.7) in grade A1, 79.1 mg/g (45.1\u0026ndash;133.6) in grade A2, and 790.3 mg/g (412.2\u0026ndash;1209.3) in grade A3 albuminuria. The overall prevalence of albuminuria was 29.1% (81/279). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes patient characteristics by albuminuria category. Several clinical complications differed significantly across groups: history of vaso-occlusive crisis (VOC) in the previous trimester (79 [41.6%] vs 23 [38.3%] vs 16 [80.0%]; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), leg ulceration (50 [26.2%] vs 15 [25.0%] vs 11 [55.0%]; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028), α-1-microglobulin positivity (105 [53.0%] vs 51 [85.0%] vs 20 [95.2%]; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and low systemic vascular resistance (SVR) (19 [22.1%] vs 4 [26.7%] vs 3 [30.0%]; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018).\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\u003eGeneral characteristics of patients studied according to albuminuria\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\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\u003eOver all\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;279)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlbuminuria grade A1 (n\u0026thinsp;=\u0026thinsp;198)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAlbuminuria grade A2 (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAlbuminuria grade A3 (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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=\"char\" char=\".\" 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\u003cp\u003e26.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e152(54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e112(56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27(45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13(61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;25 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e127(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86(43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33(55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8(38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolic acid intake\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e255(94.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e179(94.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57(95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e19(95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.514\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydroxyurea use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e101(37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73(38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19(31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9(45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.479\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66(24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51(26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of VOC (previous trimester)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e118(43.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79(41.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23(38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16(80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeg ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76(28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50(26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11(55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePriapism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3(5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetinopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43(15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32(16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8(13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAseptic necrosis of femoral head\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.933\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4(1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1(0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3(5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTabacco\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24(8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13(6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2(10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64(23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47(24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eα-1 microglobulin\u0026thinsp;\u0026ge;\u0026thinsp;12 mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e176(63.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105(53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51(85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20(95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP\u0026thinsp;\u0026ge;\u0026thinsp;6 mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e169(60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e117(59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39(65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13(61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorphology of LV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43(37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32(37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6(28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5(62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcentric remodeling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7(6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5(5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1(12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcentric LVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15(13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13(15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2(9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEccentric LVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50(43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36(41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12(57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2(25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow SVR (\u0026lt;\u0026thinsp;700)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26(23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4(26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3(30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal Kidney\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e91(82.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62(79.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20(87.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e9(100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNephromegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17(15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14(17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3(13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.420\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, absolute (n) and relative (in percent) frequencies. Abbreviations: Low SVR: Low Systemic vascular resistance; LVH: Left ventricular hypertrophy; LV Morphology: Left ventricular Morphology;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCystatin-C did not differ significantly between groups (0.84 [0.72\u0026ndash;0.93] vs 0.86 [0.74\u0026ndash;1.06] vs 0.91 [0.72\u0026ndash;1.11] mg/L; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.120). By contrast, LDH varied significantly (211.2 [195.5\u0026ndash;264.4] vs 200.6 [184.5\u0026ndash;253.0] vs 238.0 [200.0\u0026ndash;402.6] IU/L; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), as did systolic blood pressure (105.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 vs 102.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 vs 111.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 mmHg; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031). GOT and reticulocyte counts were similar across groups, as were total and direct bilirubin and CRP. Although PWV tended to be lowest in grade A3, a significant overall difference was observed (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017). TAPSE, while within the normal range, also differed (2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 vs 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 vs 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 cm; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.040). Cardiac output did not vary significantly, but SVR was lower in grade A3 than in the other groups (Table\u0026nbsp;\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\u003eBiological, hemodynamic and echocardiographic characteristics of the population studied according to Albuminuria\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\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\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAlbuminuria grade A1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAlbuminuria grade A2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAlbuminuria grade A3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105.0\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e111.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBSA, m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.51(1.42\u0026ndash;1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.51(1.42\u0026ndash;1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.48(1.38\u0026ndash;1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.53(1.44\u0026ndash;1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePWV, m/sec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eABI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVSd, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePWd, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.856\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEDD, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRVEDD, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eiLVM, g/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108.1\u0026thinsp;\u0026plusmn;\u0026thinsp;26.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108.7\u0026thinsp;\u0026plusmn;\u0026thinsp;27.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106.4\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e106.5\u0026thinsp;\u0026plusmn;\u0026thinsp;29.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVC, mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE/E'\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTRV, m/sec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAPSE, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.040\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac output, l/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.71(5.33\u0026ndash;8.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.68(5.33\u0026ndash;8.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.86(5.75\u0026ndash;8.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.03(4.91\u0026ndash;7.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.395\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVR, dynes sec/cm\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e832.5(678.9-1089.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e992.0(695.1-1141.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e825.6(669.0-1093.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e772.6(699.1-1040.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eα-1 microglobulin, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.1(7.9\u0026ndash;40.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.7(6.3\u0026ndash;30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.2(16.1\u0026ndash;57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79.7(29.3\u0026ndash;127.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACR, mg/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.2(4.2\u0026ndash;41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.6(3.4\u0026ndash;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.1(45.1-133.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e790.3(412.2-1209.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\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\" colname=\"c2\"\u003e \u003cp\u003e0.6(0.5\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6(0.5\u0026ndash;0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6(0.5\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.60(0.47\u0026ndash;0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.892\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCystatine, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85(0.73\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.84(0.72\u0026ndash;0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.86(0.74\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.91(0.72\u0026ndash;1.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeasured GFR, mL/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128.0(105.0-150.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127.0(108.0-151.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128.0(94.0-155.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e135.0(99.3-147.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.747\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrea, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.81(3.5-6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.86(3.70\u0026ndash;6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.94(3.32\u0026ndash;5.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.55(3.24\u0026ndash;6.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.785\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC x 10\u003csup\u003e6\u003c/sup\u003e, /mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6(2.3\u0026ndash;3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.6(2.2\u0026ndash;3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.68(2.26\u0026ndash;3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.89(2.33\u0026ndash;3.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.366\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\" colname=\"c2\"\u003e \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHct, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReticulocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.0(15.0\u0026ndash;18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.0(15.0\u0026ndash;18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.0(15.0\u0026ndash;18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.0(14.0-17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC x 10\u003csup\u003e3\u003c/sup\u003e, /mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.7(8.8\u0026ndash;13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1(8.9\u0026ndash;14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.5(8.5\u0026ndash;13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.1(8.2\u0026ndash;14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets x 10\u003csup\u003e3\u003c/sup\u003e, /mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156.3(150.6-163.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156.2(150.4-162.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e156.9(151.1-164.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e161.2(150.5-171.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGOT, IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.9(27.0-45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3(27.0-44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.0(26.9\u0026ndash;50.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.3(27.3\u0026ndash;47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bili, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0(0.9\u0026ndash;1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0(0.92\u0026ndash;1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00(0.92\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09(0.88\u0026ndash;1.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDirect Bili, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.30(0.24\u0026ndash;0.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30(0.24\u0026ndash;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.31(0.25\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25(0.24\u0026ndash;0.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.447\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH, IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210.3(193.2-265.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e211.2(195.0-260.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200.6(184.5\u0026ndash;253.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e238.0(200.0-402.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin, ng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e267.1(97.9-663.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e247.4(95.7-600.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e319.0(102.2\u0026ndash;761.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e276.1(171.5-569.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.539\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.5(3.3\u0026ndash;20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.1(3.2\u0026ndash;18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5(4.4\u0026ndash;24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.0(2.5\u0026ndash;15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal Hb, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.0(8.0\u0026ndash;13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.0(8.0\u0026ndash;13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.0(8.0\u0026ndash;16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.0(6.8\u0026ndash;11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (interquartile range), absolute (n) and relative (in percent) frequencies. Abbreviations: ABI: Ankle brachial index; ACR: Albuminuria-creatinine ratio; BSA: Body surface area; CRP: C-reactive protein; DBP: Diastolic blood pressure; GOT: glutamooxaloacetate transferase; Hb: Haemoglobin; Hct: Haematocrit; IVC: Inferior vena cava; LDH: Lactate dehydrogenase; LVEDD: Left ventricular end-diastolic diameter; LVEF: Left ventricular ejection fraction; SBP: Systolic blood pressure; LVMi : Indexed left ventricular mass; PW: Posterior wall; PWV: Pulse wave velocity; RBC: Red blood cells; TAPSE: Tricuspid annular plane systolic excursion; TRV: Tricuspid regurgitation time; SBP: Systolic blood pressure; SVR: Systemic vascular resistance; WBC: White blood cells.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eLDH, SBP, and PWV were markedly higher in grade A3 than in grades A1 or A2 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010, 0.031, and 0.010, respectively; Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Multiple linear regression (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) showed albuminuria was independently associated with SBP (β\u0026thinsp;=\u0026thinsp;2.56; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), LDH (β\u0026thinsp;=\u0026thinsp;1.373; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), PWV (β\u0026thinsp;=\u0026thinsp;3.279; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037), cardiac output (β\u0026thinsp;=\u0026thinsp;1.262; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029), and SVR (β = -0.081; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021), explaining 56.3% of the variance (R\u0026sup2; = 0.563).\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\u003eAssociated factors of albuminuria in the population studied (Multiple linear regression)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eꞵ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCI 95%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Constante)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.994\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-67.3\u0026nbsp;; 33.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSBP, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(2.3\u0026nbsp;; 17.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, Kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.843\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-74.9\u0026nbsp;; 62.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary α-1 microglobulin, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-1.25\u0026nbsp;; 2.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC, /mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-4.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-28.1\u0026nbsp;; 18.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH, IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.45\u0026nbsp;; 3.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePWV, m/sec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.037\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.87\u0026nbsp;; 12.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAPSE, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-26.3\u0026nbsp;; 36.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac output, L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(0.25\u0026nbsp;; 11.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVR, dyn.s/cm\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(-0.79 ; \u0026minus;\u0026thinsp;0.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eR\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.563\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations. SBP: Systolic blood pressure; BMI: Body mass index; WBC: White blood cell; LDH: Lactate dehydrogenase; PWV: Pulse wave velocity, SVR: Systemic vascular resistance\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn univariate logistic regression, α-1-microglobulin\u0026thinsp;\u0026ge;\u0026thinsp;12 mg/L, recent VOC, leg ulcers, LDH\u0026thinsp;\u0026gt;\u0026thinsp;246 IU/L, and SVR\u0026thinsp;\u0026lt;\u0026thinsp;700 dyn\u0026middot;s/cm⁵ were each associated with albuminuria (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). After multivariate adjustment, four factors remained significant: α-1-microglobulin\u0026thinsp;\u0026ge;\u0026thinsp;12 mg/L (aOR\u0026thinsp;=\u0026thinsp;3.01, 95% CI 1.80\u0026ndash;4.02; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016), recent VOC (aOR\u0026thinsp;=\u0026thinsp;2.71, 95% CI 1.22\u0026ndash;4.21; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024), LDH\u0026thinsp;\u0026gt;\u0026thinsp;246 IU/L (aOR\u0026thinsp;=\u0026thinsp;3.57, 95% CI 2.40\u0026ndash;6.13; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), and SVR\u0026thinsp;\u0026lt;\u0026thinsp;700 dyn\u0026middot;s/cm⁵ (aOR\u0026thinsp;=\u0026thinsp;1.91, 95% CI 1.51\u0026ndash;7.15; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociated factors of albuminuria in the population studied (Logistic regression)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaOR (CI 95%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eaOR (CI 95%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary α-1 microglobuline, mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \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 \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.02(2.09\u0026ndash;4.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.01(1.80\u0026ndash;4.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of VOC (previous trimester)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \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 \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.38(1.79\u0026ndash;5.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.71(1.22\u0026ndash;4.21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeg ulcer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \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 \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36(1.77\u0026ndash;3.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.36(0.39\u0026ndash;4.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\u0026thinsp;\u0026gt;\u0026thinsp;246 IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \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 \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.91(1.59\u0026ndash;3.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.57(2.40\u0026ndash;6.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSVR\u0026thinsp;\u0026lt;\u0026thinsp;700 dyn.s/cm\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \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 \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.37(1.50\u0026ndash;3.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.91(1.51\u0026ndash;7.15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations. LDH: Lactate dehydrogenase; PWV: Pulse wave velocity, SVR: Systemic vascular resistance; VOC: Vaso-occlusive crise\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study reported a 29.1% prevalence of albuminuria among adults with sickle cell disease (SCD), including 21.5% with grade A2 and 7.5% with grade A3 albuminuria. Albuminuria was independently associated with systolic blood pressure (SBP), lactate dehydrogenase (LDH), pulse wave velocity (PWV), increased cardiac output, reduced systemic vascular resistance (SVR), urinary α-1 microglobulin, and recent vaso-occlusive crises (VOC). Taken together, these findings support the concept that albuminuria in SCD reflects a multifactorial cardiorenal injury resulting from the interaction between hemolysis, tubular dysfunction, and systemic vascular alterations rather than isolated glomerular damage.\u003c/p\u003e \u003cp\u003eThe prevalence of albuminuria observed in our adult cohort was higher than that reported among Congolese children by Aloni et al. (18%) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and was comparable to estimates from McPherson et al. (20.7%) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and Ataga et al. (26%) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, it remained lower than prevalences reported by Kambale-Kombi et al. (86.7%) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], Laurin et al. (45%) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], and Drawz et al. (64%) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These variations likely reflect differences in age distribution, study design, and therapeutic exposure, particularly the use of RAAS inhibitors, hydroxyurea, and statins [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Persistent albuminuria has been reported to occur more frequently in patients with higher baseline albuminuria or delayed initiation of hydroxyurea therapy, particularly after childhood [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe median albuminuria levels observed in our cohort were comparable to those reported by Drawz et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] but lower than those described by Ataga et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The pathophysiology of renal injury in SCD is complex and involves multiple interacting mechanisms including hyperfiltration, oxidative stress, and chronic intravascular hemolysis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Hyperfiltration, a hallmark of early sickle nephropathy, has been reported in both pediatric and adult populations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and has been associated with progressive glomerular remodeling and albumin leakage [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, elevated SBP was significantly associated with albuminuria. Increased renal plasma flow in SCD, often driven by elevated cardiac output and reduced SVR, may increase glomerular perfusion pressure and contribute to glomerular stress [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Similar observations were reported by Gosmanova et al., who identified SBP as a predictor of CKD progression in SCD populations [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These findings support the concept that systemic hemodynamic alterations contribute to renal injury.\u003c/p\u003e \u003cp\u003eChronic intravascular hemolysis represents another major contributor to renal damage. Reduced nitric oxide bioavailability, increased endothelin-1 activity, oxidative stress, and endothelial dysfunction have been described in SCD and have been associated with microvascular injury and albuminuria [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The higher prevalence of leg ulcers among patients with grade A3 albuminuria in our cohort further supports the link between systemic vasculopathy and renal involvement.\u003c/p\u003e \u003cp\u003eLDH, a surrogate marker of intravascular hemolysis, was significantly associated with albuminuria severity. Chronic hemolysis has been linked to hyperfiltration and glomerular hypertrophy through heme-mediated vascular and inflammatory pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In addition, chronic anemia may increase cardiac output and contribute to glomerular hemodynamic stress, which may explain the association between elevated cardiac output and albuminuria observed in our study. Previous studies have also shown that hydroxyurea therapy may reduce hyperfiltration and albuminuria, further supporting the role of hemolysis in renal injury [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTubular dysfunction also appears to play a central role in SCD-related renal injury. Urinary α-1 microglobulin, a marker of proximal tubular injury, was independently associated with albuminuria, consistent with findings reported by Elsherif et al. [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Tubular injury in SCD has been attributed to recurrent ischemia-reperfusion injury during VOC episodes and oxidative stress. Histopathological studies demonstrating hemosiderin deposition in proximal tubular cells further support the relationship between hemolysis and tubular injury [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. These findings suggest that albuminuria in SCD may partly reflect tubular-glomerular crosstalk rather than isolated glomerular pathology.\u003c/p\u003e \u003cp\u003eAlthough CRP was not independently associated with albuminuria in our cohort, inflammation remains an important component of SCD pathophysiology. Hemolysis-related oxidative stress and inflammatory cytokine release, including TNF-α and IL-1β, have been implicated in endothelial activation and chronic renal injury [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVascular dysfunction further contributes to renal vulnerability in SCD. Increased PWV, reflecting arterial stiffness, was associated with albuminuria, consistent with findings reported by Ranque et al. [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. PWV reflects structural and functional alterations in medium and small arteries that may predispose to renal microvascular injury [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Reduced SVR, commonly observed in SCD due to nitric oxide-mediated vasodilation, has also been associated with increased renal plasma flow and filtration stress [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTaken together, these findings support an integrated cardiorenal model of renal injury in sickle cell disease. As illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, chronic intravascular hemolysis promotes nitric oxide depletion, oxidative stress, and inflammation, leading to systemic vascular dysfunction characterized by reduced systemic vascular resistance, increased cardiac output, and arterial stiffness. These hemodynamic alterations promote glomerular hyperfiltration and renal stress. Concurrently, recurrent vaso-occlusive events and hemolysis-related injury contribute to tubular dysfunction, reflected by increased urinary α-1 microglobulin. The combined effects of vascular dysfunction, glomerular stress, and tubular injury ultimately lead to albuminuria, which may represent an integrated marker of systemic vascular and renal injury rather than an isolated glomerular abnormality.\u003c/p\u003e \u003cp\u003eThis study has several limitations. The absence of additional markers of hemolysis and oxidative stress, such as haptoglobin, limited characterization of hemolytic burden. Albuminuria was assessed at a single time point, precluding evaluation of persistence. Nevertheless, this study represents the first investigation in the Democratic Republic of Congo combining direct measurement of glomerular filtration rate using iohexol clearance with albuminuria assessment and vascular evaluation using PWV, parameters recognized as valuable tools for early detection of renal dysfunction in recent SCD-specific recommendations [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eClinical Implications\u003c/h3\u003e\n\u003cp\u003eThe present findings have several important clinical implications for the management of adults with sickle cell disease. First, the high prevalence of albuminuria observed in this study supports systematic screening for renal involvement even in patients in steady-state condition. Second, the strong association between albuminuria and markers of tubular injury, hemolysis, and vascular dysfunction suggests that renal risk assessment in sickle cell disease should not rely solely on glomerular markers but rather adopt an integrated cardiorenal approach. The identification of urinary α-1 microglobulin as an independent determinant of albuminuria highlights the potential value of tubular biomarkers for early detection of renal injury and improved risk stratification. In addition, the association between albuminuria and systemic hemodynamic alterations, including increased arterial stiffness and reduced systemic vascular resistance, underscores the need for multidisciplinary monitoring incorporating cardiovascular evaluation. Early identification of patients at higher renal risk may allow timely implementation of therapeutic strategies, including optimization of hydroxyurea therapy, blood pressure control, and potential use of renin\u0026ndash;angiotensin\u0026ndash;aldosterone system inhibitors. Finally, these findings support the need for longitudinal studies to determine whether combined biomarker-based screening strategies can improve renal outcomes in adults with sickle cell disease.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn adults with sickle cell disease, albuminuria is common and appears to reflect a multidimensional renal vulnerability driven by the interaction between chronic hemolysis, tubular injury, and systemic vascular dysfunction. These findings support the need for integrated renal risk assessment strategies beyond isolated glomerular markers. Longitudinal studies incorporating repeated albuminuria measurements and multimodal renal biomarkers are required to clarify the prognostic significance and therapeutic implications of albuminuria in this population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors wish to thank the various medical centres and their coordinators for collecting data, particularly Dr. Grace Ngoy and Mrs. Ledya, as well as the team of nurses and laboratory technicians from the specialized clinics of Kinshasa. We also extend our sincere appreciation to Professors Pierre Delanaye, Etienne Cavalier, and the entire Sart Tilman Laboratory team at the University Hospital of Li\u0026egrave;ge for their invaluable support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants were provided informed consent during the study accordance with the Helsinki guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report there are no competing interests to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors of the manuscript participated in the realization and preparation of the study. YE, JB, JRM, and ES designed the study; acquired, analyzed, and interpreted the data; and drafted and revised the manuscript. AN performed statistical analysis and interpreted the data. BM performed the echocardiograms. DL performed renal ultrasounds. YN, MFM, BM, VM, FK, EK, BN, JM, AN and ES revised the manuscript. All authors (s) read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was partly supported by the SFNDT (French Speaking Society of Nephrology, Dialysis, and Transplantation)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data can be made available via email to anyone who wishes to contact Yannick Engole at the following address: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHamideh D, Alvarez O. 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Clin Hemorheol Microcirc. 2018; 68(2\u0026ndash;3): 205\u0026ndash;221, 2018. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3233/CH-189008\u003c/span\u003e\u003cspan address=\"10.3233/CH-189008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Albuminuria, α-1 microglobulin, steady-state sickle cell disease, adults, hemolysis, vascular resistance","lastPublishedDoi":"10.21203/rs.3.rs-9058136/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9058136/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAlbuminuria is an early marker of glomerular injury in sickle cell disease (SCD) and predicts progressive renal impairment. Data on albuminuria among adults with SCD in sub-Saharan Africa remain limited. This study aimed to determine the prevalence of albuminuria and identify associated factors in adults with steady-state SCD in Kinshasa, Democratic Republic of Congo.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a multicenter cross-sectional study including 279 adults (\u0026ge;\u0026thinsp;18 years) with steady-state SCD. Albuminuria was assessed using the urinary albumin-to-creatinine ratio (UACR) and categorized according to KDIGO criteria. Glomerular filtration rate (GFR) was measured by plasma iohexol clearance. Cardiac function was evaluated by Doppler echocardiography, and arterial stiffness was assessed using pulse wave velocity (PWV). Multivariate linear and logistic regression analyses were performed to identify independent determinants of albuminuria.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe overall prevalence of albuminuria was 29.1%, including 21.5% grade A2 and 7.5% grade A3. Albuminuria was associated with elevated systolic blood pressure (SBP), lactate dehydrogenase (LDH), PWV, increased cardiac output, and reduced systemic vascular resistance (SVR). In multivariate analysis, urinary α-1 microglobulin\u0026thinsp;\u0026ge;\u0026thinsp;12 mg/L (aOR 3.01, 95% CI 1.80\u0026ndash;4.02), recent vaso-occlusive crisis (aOR 2.71, 95% CI 1.22\u0026ndash;4.21), LDH\u0026thinsp;\u0026gt;\u0026thinsp;246 IU/L (aOR 3.57, 95% CI 2.40\u0026ndash;6.13), and SVR\u0026thinsp;\u0026lt;\u0026thinsp;700 dyn\u0026middot;s/cm⁵ (aOR 1.91, 95% CI 1.51\u0026ndash;7.15) remained independently associated with albuminuria.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNearly one-third of adults with steady-state SCD had albuminuria. Hemolysis, tubular injury, recent vaso-occlusive events, and vascular dysfunction were key determinants, highlighting the interplay between glomerular hyperfiltration and systemic vasculopathy. Longitudinal studies are warranted to assess persistence and progression of renal involvement.\u003c/p\u003e","manuscriptTitle":"Albuminuria Is Associated with Multidimensional Cardiorenal injury in Adults with Steady-State Sickle Cell Disease: A Multicenter Study with Measured GFR","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 09:52:03","doi":"10.21203/rs.3.rs-9058136/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-13T09:03:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-11T19:22:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222457475329115024605235231055870808279","date":"2026-03-30T00:24:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-29T21:19:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100423289468451666896794222223910164087","date":"2026-03-29T20:48:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-29T14:38:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117912933017707416854673338448329831471","date":"2026-03-29T14:31:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-29T10:50:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-11T16:08:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-10T11:44:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-10T11:43:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2026-03-07T11:38:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a27081a4-d230-46e1-94db-9ad241d5571e","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-03T14:08:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 09:52:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9058136","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9058136","identity":"rs-9058136","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}