Factors related to serum brain-derived neurotrophic factor level in chronic hemodialysis patients

Factors related to serum brain-derived neurotrophic factor level in chronic hemodialysis patients | 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 Factors related to serum brain-derived neurotrophic factor level in chronic hemodialysis patients Harumichi Higashi, Reiko Nishichi, Masakazu Washio, Kazuhiko Tsuruya, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7827190/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 Brain-derived neurotrophic factor (BDNF) may play a role in glucose and lipid metabolism as well as mental health. We previously reported a negative association between BDNF levels and mental health in hemodialysis (HD) patients. Cardiovascular disease (CVD) is a common cause of death in patients undergoing HD. However, we have not yet evaluated the associations between serum BDNF levels and risk factors for CVD in HD patients. Methods A cross-sectional study was conducted to evaluate the factors associated with serum BDNF levels in HD patients without active mental disorders. Seventy-seven HD patients were divided into two groups according to their serum BDNF levels: (i) the high BDNF group (BDNF>12 ng/mL: n=39), and (ii) the low BDNF group (BDNF < 12 ng/mL: n=38). Demographic and laboratory parameters were compared between the two groups. Results The values for total cholesterol, low-density lipoprotein (LDL) - cholesterol, body mass index, white blood cell count and platelet count were higher in the high BDNF group than in the low BDNF group. Higher serum total cholesterol levels, white blood cell counts and platelet counts were associated with an increased risk of higher serum BDNF levels even after controlling for age and sex. Furthermore, a higher platelet count remained a significant risk factor for higher BDNF levels even after controlling for higher total serum cholesterol levels and white blood cell counts. Conclusions Since platelets are suggested to play important roles not only in the initiation but also in the progression of atherosclerosis, BDNF might play a role in the development of atherosclerosis in patients on HD. Brain-derived neurotrophic factor Cardiovascular disease Chronic renal failure Hemodialysis Figures Figure 1 Background According to an annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry, there were 3,447,474 dialysis patients in Japan by the end of 2022 [ 1 ]. Diabetes mellitus (DM) (39.5%) is a leading cause of end-stage kidney disease (ESKD) that requires HD therapy [ 1 ]. Cardiovascular disease(CVD) is highly common in patients with ESKD [ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]. Patients on HD have comorbidities related to the risk of cardiovascular diseases (i.e., hypertension [ 3 ], [ 4 ], [ 5 ], DM [ 1 ], [ 2 ], [ 4 ], [ 5 ], and dyslipidemia [ 3 ], [ 4 ], [ 5 ]). Therefore, secondary prevention (i.e., early detection and treatment) of treatable risk factors is important to reduce the risk of CVD in HD patients. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. In addition to its neurotrophic and synaptotrophic actions, it promotes the growth and survival of neurons [ 6 ]. BDNF is suggested to play a role not only in learning and memory [ 7 ] but also in glucose and lipid metabolism and energy homeostasis [ 8 ], [ 9 ]. BDNF is present in the nervous system and peripheral tissues [ 10 ] and is also found in the blood [ 10 ]. In addition, plasma BDNF has been reported to be correlated with multiple risk factors for metabolic syndrome (e.g., obesity, blood pressure, total cholesterol and triglycerides) and cardiovascular dysfunction [ 11 ]. Zoladz et al. [ 12 ] reported that serum BDNF levels were lower in HD patients than in age-and sex-matched controls. In our previous study [ 13 ], serum BDNF levels in HD patients were significantly lower than those in healthy subjects. In addition, serum BDNF levels were lower in the psychiatric distress group than in the non-psychiatric distress group of HD patients [ 13 ]. However, we did not evaluate the association between serum BDNF levels and risk factors for CVD. Therefore, the present study was conducted to evaluate the factors associated with the serum BDNF levels in HD patients without active psychiatric disease. Subjects and methods In November 2006, 173 HD patients of ≥ 50 years old or older received HD therapy at St. Mary's Hospital in Kurume City, Fukuoka Prefecture, Japan. Of these, 59 were excluded. Patients with active psychiatric diseases, acute infections, or acute complications due to uremia were excluded because they were treated with antidepressant agents or other drugs. The other exclusion criteria were severe cognitive impairment, depression requiring major tranquilizers, and poor activity of daily living (ADL) ability. The final exclusion criterion was patients who underwent a short duration of HD treatment (i.e., < 6 months). Therefore, 114 HD patients were asked to participate in this study. Of these, 88 agreed to participate. Among them, 11 patients with incomplete data from questionnaires and biochemical tests were excluded from this study. Therefore, the study subjects were 77 HD patients (females, n = 26, males, n = 51) with a mean age of 62.8 ± 8.3 (SD) years. In addition to HD patients, 15 healthy volunteers with a mean age of 55.6 ± 4.0 years agreed to donate blood samples to for the measurement of BDNF. Biochemical and hematologic data were obtained prior to dialysis on December 1st and 2nd, 2006, respectively. Other clinical variables, including HD duration, primary renal disease, and comorbid diseases, were also documented. The body mass index (BMI) was calculated as the participant’s dry weight in kilograms divided by the square of their height in meters. Blood pressure was measured before the dialysis procedure in the supine position after bed rest. Hypertension was defined as present if patients had a systolic blood pressure of ≥ 140 mmHg or higher and/or a diastolic blood pressure of ≥ 90 mmHg [ 14 ]. The blood tests included a complete blood count, serum chemistry, blood glucose, and hemoglobin A 1 c (HbA 1 c), which were examined in the St. Mary's Hospital laboratory. Serum BDNF levels were measured using a BDNF Emax Immunoassay System Kit (Promega, Madison, WI, USA). The cardiothoracic ratio (CTR) was calculated by dividing the cardiac diameter by the thoracic diameter on chest radiography (posterior-anterior view) before HD, whereas ischemic electrocardiogram (ECG) changes were defined as ST-depression detected by the standard twelve-lead ECG recorded before HD. Ethics All participants received oral and written information about the experimental procedures before providing their written informed consent. This study was approved by the Ethical Committees of St. Mary's Hospital (0611-02, 24–0702) and St. Mary's College (H18-012). Statistical analysis The mean serum BDNF level (± SD) of HD patients was 12.4 ± 5.4. HD patients were divided into two groups according to their serum BDNF level (i.e., with a cutoff value of serum BDNF 12 ng/mL): (i) the high BDNF group (BDNF > 12 ng/mL: n = 39), and (ii) the low BDNF group (BDNF ≤ 12 ng/mL: n = 38). Statistical analyses were performed using Statistical Analysis System (SAS Institute, Cary, NC, USA). The Mann-Whitney U test or chi-square test was used to compare the high and low BDNF groups. An unconditional logistic model was applied to evaluate the odds ratios (ORs) and their 95% confidence intervals (CIs) with adjustments for several covariates. The CORR procedure was used to compute the Pearson and Spearman’s rank correlation coefficients. All p-values for the statistical tests were two-tailed, and a p-values of < 0.05 were considered to indicate statistical significance. Results Table 1 presents the characteristics of the participants. The characteristics of the participants did not differ between the high and low BDNF groups. Table 1 Characteristics of participants according to serum BDNF Factors High BDNF Group (n = 39) Low BDNF group (n = 38) p-value Age, years 62.9 ± 8.5 62.6 ± 8.2 0.85 Males, n (%) 25 (64.1%) 26 (68.4%) 0.69 Duration of dialysis, years 14.5 ± 14.9 15.0 ± 15.6 0.89 Diabetic nephropathy, n (%) 11 (28.2%) 10 (26.3%) 0.85 Cardiothoracic ratio, % 51.2 ± 3.8 51.5 ± 5.6 0.80 Ischemic findings on ECG, n (%) 3 (7.7%) 6 (15.8%) 0.27 Systolic blood pressure, mmHg 126 ± 15 129 ± 18 0.44 Diastolic blood pressure, mmHg 67 ± 7 68 ± 6 0.85 Ischemic heart disease, n (%) 3 (7.7%) 6 (15.8%) 0.27 Cerebrovascular disease, n (%) 3 (7.7%) 2 (5.3%) 0.66 Continuous data are expressed as the mean ± SD and were examined using the Mann-Whitney U-test. Categorical data are expressed as the number with percentage and were examined using the chi-square test. BDNF, brain-derived neurotrophic factor; ECG, electrocardiogram Table 2 displays the laboratory data and body mass index (BMI) of the participants based on their serum BDNF levels. Total cholesterol, LDL-cholesterol, body mass index, white blood cell count and platelet count were higher in the high BDNF group than in the low BDNF group. Table 2 Laboratory data and body mass index of participants according to serum BDNF Factors Higher BDNF Group (n = 39) Lower BDNF group (n = 38) p-value BDNF (ng/mL) 17.0 ± 3.0 7.6 ± 2.7 < 0.01 Total cholesterol (mg/dL) 156.4 ± 34.6 138.3 ± 25.4 0.01 LDL-cholesterol (mg/dL) 80.6 ± 27.3 69.4 ± 21.9 0.049 Triglyceride (mg/dL) 103.9 ± 55.5 88.1 ± 39.2 0.15 HDL-cholesterol (mg/dL) 48.6 ± 13.9 45.5 ± 12.4 0.32 Adiponectin (ng /ml) 15.3 ± 9.8 14.4 ± 6.3 0.65 Total protein (mg/dL) 6.9 ± 0.4 6.8 ± 0.6 0.95 Albumin (mg/dL) 3.8 ± 0.2 3.7 ± 0.3 0.20 Blood sugar (mg/dL) 118.1 ± 31.9 117.3 ± 40.7 0.92 Hemoglobin A1c (%) 5.14 ± 0.96 5.01 ± 0.90 0.54 Body mass index (kg/m 2 ) 22.2 ± 3.9 20.4 ± 2.6 0.02 White blood cell (x10 2 /mm 3 ) 60.7 ± 15.6 51.0 ± 17.0 0.01 Red blood cell (x10 4 /mm 3 ) 333 ± 48 323 ± 49 0.33 Hemoglobin (g/dL) 10.3 ± 0.9 10.1 ± 1.3 0.46 Platelets (x10 4 /mm 3 ) 20.2 ± 4.4 13.1 ± 4.3 < 0.01 Intact PTH (pg/mL) 297 ± 299 286 ± 445 0.92 Phosphate (mg/dL) 5.0 ± 0.8 5.0 ± 1.0 0.75 Calcium (mg/dL) 9.4 ± 0.6 9.3 ± 0.6 0.93 Data are expressed as the mean ± SD and were examined using the Mann-Whitney U-test. BDNF, brain-derived neurotrophic factor; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PTH, parathyroid hormone. Table 3 shows age-and sex-adjusted ORs and 95% CIs for higher BDNF levels with respect to laboratory data and BMI. Higher serum cholesterol levels (> 147 mg/dl vs. ≤147 mg/dl: OR = 2.82, 95% CI = 1.09–7.32), white blood cell counts (> 5400/mm 3 vs. ≤5400/mm 3 ; OR = 2.74, 95% CI = 1.08–6.98) and platelet counts (> 160,000/mm 3 vs. ≤160,000/mm 3 ; OR = 36.90, 95% CI = 10.10-134.83) were associated with an increased risk of higher BDNF even after adjusting for age and sex, whereas higher BMI (> 21 kg/m 2 vs. ≤21 kg/m 2 ; OR = 2.50, 95% CI = 0.97–6.46) tended to be associated with higher BDNF levels, but failed to reach statistical significance. Table 3 Factors related to high serum BDNF and their age- and sex-adjusted odds ratios and 95% confidence intervals Factors High BDNF Group (n = 39) Low BDNF group (n = 38) Age and sex-adjusted odds ratio (95% confidence intervals) Age and sex- adjusted p-value Total cholesterol > 147 mg/dL 22 (56.4%) 12 (31.6%) 2.82 (1.09–7.32) 0.03 LDL–cholesterol > 75 mg/dL 18 (46.2%) 13 (34.2%) 1.60 (0.63–4.05) 0.33 White blood cell count > 5400/mm 3 24 (61.5%) 14 (36.8%) 2.74 (1.08–6.98) 0.03 Platelet count > 160,000/mm 3 33 (84.6%) 5 (13.2%) 36.90 (10.10–134.83) 21 kg/m 2 21 (53.8%) 12 (31.6%) 2.50 (0.97–6.46) 0.06 Data are expressed as the number with percentage༎ BDNF, brain-derived neurotrophic factor; LDL, low-density lipoprotein. Even after adjusting for age, sex and all factors in Table 3 , a higher platelet count (> 160,000/mm 3 vs. ≤ 160,000/mm 3 ; OR = 60.89, 95% CI = 10.38-357.29) showed a significantly increased OR (not shown in the table). As shown in Fig. 1 , a significantly positive relationship was observed between platelet count and serum BDNF levels in the present study (Spearman rank correlation: r = 0.76, p < 0.01). Discussion BDNF has been suggested to play a role in glucose and lipid metabolism and energy homeostasis [ 8 ], [ 9 ]. In the present study, total cholesterol, LDL-cholesterol, and body mass index were higher in the high BDNF group (BDNF > 12 ng/mL) than in the low BDNF group (BDNF ≤ 12 ng/mL). The results of the present study (mean age 62.8 years) are consistent with the results of the Baltimore Longitudinal Study of Aging (mean age: males, 71.9 years; females, 70.3 years) [ 6 ], [ 11 ]. They reported that BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol in females whereas BDNF was positively correlated with diastolic blood pressure, and triglycerides in males [ 11 ]. Krabbe et al. [ 15 ] reported an inverse association between plasma BDNF and fasting plasma glucose levels. In their study, plasma levels of BDNF were lower in patients with type 2 DM than in those without DM, and were lower in obese participants than in non-obese participants [ 15 ]. In contrast, Suwa et al. [ 9 ] reported that serum BDNF levels were higher in patients with early-stage DM than in healthy subjects. In their study [ 9 ], serum BDNF levels were positively associated with BMI, body fat percentage, triglyceride level, fasting blood glucose level and insulin resistance score among patients with early-stage DM. In the present study, the proportions of diabetic nephropathy, blood sugar and hemoglobin A1c did not differ between the high- and low- BDNF groups, which may be partly due to the small number of diabetic patients in the present study (i.e., 11 of 39 HD patients [28.2%] in the high BDNF group, and 10 out of 38 HD patients [26.3%] in the low BDNF group). We excluded the following patients: (1) patients with active psychiatric diseases, infections, or acute complications due to uremia; (2) patients with severe cognitive impairment, depression requiring major tranquilizers, or poor ADL ability; and (3) patients who underwent short-duration HD treatment (i.e., < 6 months). Therefore, further studies with larger numbers of HD patients are recommended to explain the findings of the present study. Hypertension (including prehypertension), which is major risk factors for coronary artery disease (CAD) [ 16 ], [ 17 ], and left ventricular hypertrophy (LVH), are highly common in patients with ESRD [ 4 ]. Hypertension and anemia are risk factors for LVH [ 4 ], [ 18 ], and LVH increases the risk of mortality in HD patients [ 4 ], [ 19 ]. Therefore, secondary prevention (i.e., early detection and treatment) of treatable risk factors is important to reduce the risk of CVD. In the present study, however, the degree of hypertension (i.e., systolic blood pressure, diastolic blood pressure), degree of anemia (i.e., red blood cell counts or hemoglobin), and CTR did not differ between the higher and lower groups. In contrast, the average CTR was > 50% in both groups. HD-induced stress (e.g., high arteriovenous blood flow, hemodynamic stress due to rapid volume contraction, and a significant amount of fluid weight between HD sessions) [ 20 ] may partly explain the increase in CTR. Amadio et al. [ 21 ] reported that plasma BDNF levels in patients with CAD were lower than those in healthy subjects. Furthermore, plasma BDNF was lower in patients with stable angina than in patients with acute myocardial infarction CAD patients in their study [ 21 ]. In addition, Kaess et al. [ 21 ] [ 22 ] reported that serum BDNF was inversely associated with the cardiovascular disease risk in the community in a cohort study (i.e., the Framingham Heart Study). In the present study, the proportion of HD patients with CAD was two times that in the low BDNF group than in the high BDNF group (15.8% vs. 7.7%), however this difference was not statistically significant because of the small number of participants in the present study. Platelet counts in HD patients may decrease during HD because platelet counts in patients on continuous ambulatory peritoneal dialysis (CAPD) are closer to the normal range [ 23 ]. There are several possible explanations for a decrease in the platelet count. First, heparin, which is used as an anticoagulant for HD patients, is known to promote platelet agglutination [ 23 ]. Exposure to heparin tends to cause platelets to self-aggregate [ 23 ]. Second, dialyzer hypersensitivity symptoms are infrequently associated with a reduction in platelet counts, and some activation and aggregation of platelets during dialysis may be due not only to the exposure of blood to the dialyzer but also to the exposure of blood to the roller pump segment of the dialysis tubing or to microbubbles [ 23 ]. In the present study, the platelet count in the high BDNF group was higher than the in the low BDNF group. In addition, a positive relationship was observed between platelet count and serum BDNF level in the present study (Spearman rank correlation: r = 0.76, p < 0.01) (Fig. 1 ), which may be partly explained as follows: since platelets bind, store, and release BDNF upon activation at the site of traumatic injury to facilitate tissue repair [ 10 ], platelets may release BDNF upon activation of injured blood cells during the dialysis procedure. Therefore, there may be a positive relationship between serum BDNF levels and platelet counts in patients undergoing HD. HD patients are at a high risk of contracting blood-borne infections such as hepatitis B virus [ 24 ], [ 25 ] and hepatitis C virus [ 25 ], [ 26 ]. Although isolation of carriers and screening of blood donors may be effective in the prevention of blood-borne viral infections among HD patients [ 27 ], hepatitis B and C remain prevalent in dialysis patients [ 25 ]. Thrombocytopenia is common in patients with chronic liver diseases [ 28 ], which may be partly explained by the fact that chronic liver disease (hepatitis B, hepatitis C, and nonalcoholic fatty liver disease) is prevalent in dialysis patients [ 25 ]. Iwamoto et al. [ 29 ] reported a negative association between platelet counts and years of HD among Japanese HD patients. The present study had several limitations. First, it was a cross-sectional study. Therefore, we could not determine whether factors related to higher serum BDNF levels were the cause or result of higher serum BDNF. Second, the number of participants in the present study was not sufficient to evaluate the factors in a multivariate analysis. Third, the participants in the present study were HD patients. Therefore, the findings of the present study were influenced not only by the uremic condition itself but also by the intermittent dialysis procedure (3 days a week). Fourth, echocardiographic examinations were not performed in this study. Conclusions In summary, serum total cholesterol level, white blood cell count and platelet count were positively associated with serum BDNF levels even after controlling for age and sex. Furthermore, platelet count remained a significant risk factor for increased BDNF levels even after controlling for age, sex, total serum cholesterol level, and white blood cell count. Since platelets are suggested to play important roles not only in the initiation but also in the progression of atherosclerosis [ 30 ], further studies are needed to clarify the role of serum BDNF in HD patients. A part of this study was presented at the 58th Annual Meeting of the Japanese Society for Dialysis Therapy in Fukuoka in 2013. Abbreviations BDNF: Brain-derived neurotrophic factor HD: Hemodialysis CVD: Cardiovascular disease LDL: Low-density lipoproteins DM: Diabetes mellitus ADL: Activities of daily living BMI: Body mass index CVD: Cardiovascular disease HbA1c: Hemoglobin A 1 c ECG: Electrocardiogram ORs: Odds ratios LVH: Left ventricular hypertrophy CAD: Coronary artery disease CAPD: Continuous ambulatory peritoneal dialysis CTR: Cardiothoracic ratio Declarations Founding Not applicable Ethics approval and consent to participate Informed consent was obtained from all the participants. This study was approved by the Ethical Committees of St. Mary's Hospital (0611-02, 24–0702) and St. Mary's College (H18-012). Consent for publication Not applicable Competing interests The authors declare no competing interests. Author Contribution H.H., R.N., M.W., and K.T. contributed to the conception and design of the study and contributed to the analysis and interpretation of the data. H.H., R.N., M.W., K.T., K.T., T.N., M.K, and T.K. contributed to the critical reading of the article for important intellectual content, final approval of the article, and drafting of the article. Acknowledgement This study was partly supported by St. Mary’s Hospital, and St. Mary's College. Data Availability All data generated or analysed during this study are included in this published article. References Hanafusa N, Abe M, Joki N, Hoshino J, Taniguchi M, Kikuchi K, et al. 2022 annual dialysis data report, JSDT renal data registry. 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Higashi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYBACA2YgwdggIYciCCKYCWkxZmAjWgsDWAtDYgO6FpzAnJ394sefOyzS589vYN3wc89hBt325g0MH/cwsJvj0GLZzFMszXtGInfDMQa2mz3PDjOYnTlWwDjjGQOzZQMOhx3mSZBmbANqYeP/doPnwOH6bTdyDJh5DjAwGxzAqSX55882iXT5NqAtfw4Abbn/hpAW9mMSvG0SCQxAh93mAWm5wUPQFjZroBbDDccS2G7LHEgH+iWt4OCMAxK4/XL++OObP9vq5OWbD7DdfHPAmsHs+OGNDz4csEnGFWIMDDwosdAMJoFOkkjGHTvsD5B5dXCWHf4IHQWjYBSMghEEAJBjW9/ElYjRAAAAAElFTkSuQmCC","orcid":"","institution":"St. Mary’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Harumichi","middleName":"","lastName":"Higashi","suffix":""},{"id":551583975,"identity":"b8d05490-e28f-4ce2-834a-f05e32504f30","order_by":1,"name":"Reiko Nishichi","email":"","orcid":"","institution":"St. Mary’s College","correspondingAuthor":false,"prefix":"","firstName":"Reiko","middleName":"","lastName":"Nishichi","suffix":""},{"id":551583980,"identity":"a7a945a0-660e-4754-8afc-b1e5e1dd7ffd","order_by":2,"name":"Masakazu Washio","email":"","orcid":"","institution":"St. Mary’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masakazu","middleName":"","lastName":"Washio","suffix":""},{"id":551583982,"identity":"d45a52fa-fce3-4f46-8d19-3b1820b2b381","order_by":3,"name":"Kazuhiko Tsuruya","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kazuhiko","middleName":"","lastName":"Tsuruya","suffix":""},{"id":551583983,"identity":"6052b1d7-60f6-47f3-9e30-f6ab8b50b243","order_by":4,"name":"Kumiko Torisu","email":"","orcid":"","institution":"Kyushu 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07:45:34","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":84842,"visible":true,"origin":"","legend":"","description":"","filename":"9c42fb7fbb6c49919a12599680e35b851structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7827190/v1/774c9d637bb91babeec3f9ed.xml"},{"id":97119503,"identity":"289a2d4e-4d19-4485-a3bf-5f67d661da74","added_by":"auto","created_at":"2025-12-01 07:45:34","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92661,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7827190/v1/80cef184f14003bad80a0e10.html"},{"id":97119495,"identity":"e9b131f0-228c-4d2a-af13-1ccff5c4e3b3","added_by":"auto","created_at":"2025-12-01 07:45:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110261,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between platelet count and the serum BDNF level in HD patients.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7827190/v1/24a444aee7419bbf383a399e.png"},{"id":97248449,"identity":"6e9cd018-fa1e-4527-914e-d1a6cf449805","added_by":"auto","created_at":"2025-12-02 12:58:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":795349,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7827190/v1/d703f64f-81f3-4274-85e9-704291f288bc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Factors related to serum brain-derived neurotrophic factor level in chronic hemodialysis patients","fulltext":[{"header":"Background","content":"\u003cp\u003eAccording to an annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry, there were 3,447,474 dialysis patients in Japan by the end of 2022 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Diabetes mellitus (DM) (39.5%) is a leading cause of end-stage kidney disease (ESKD) that requires HD therapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCardiovascular disease(CVD) is highly common in patients with ESKD [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Patients on HD have comorbidities related to the risk of cardiovascular diseases (i.e., hypertension [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], DM [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and dyslipidemia [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]). Therefore, secondary prevention (i.e., early detection and treatment) of treatable risk factors is important to reduce the risk of CVD in HD patients.\u003c/p\u003e\u003cp\u003eBrain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. In addition to its neurotrophic and synaptotrophic actions, it promotes the growth and survival of neurons [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. BDNF is suggested to play a role not only in learning and memory [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] but also in glucose and lipid metabolism and energy homeostasis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. BDNF is present in the nervous system and peripheral tissues [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and is also found in the blood [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition, plasma BDNF has been reported to be correlated with multiple risk factors for metabolic syndrome (e.g., obesity, blood pressure, total cholesterol and triglycerides) and cardiovascular dysfunction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eZoladz et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] reported that serum BDNF levels were lower in HD patients than in age-and sex-matched controls. In our previous study [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], serum BDNF levels in HD patients were significantly lower than those in healthy subjects. In addition, serum BDNF levels were lower in the psychiatric distress group than in the non-psychiatric distress group of HD patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, we did not evaluate the association between serum BDNF levels and risk factors for CVD.\u003c/p\u003e\u003cp\u003eTherefore, the present study was conducted to evaluate the factors associated with the serum BDNF levels in HD patients without active psychiatric disease.\u003c/p\u003e"},{"header":"Subjects and methods","content":"\u003cp\u003eIn November 2006, 173 HD patients of \u0026ge;\u0026thinsp;50 years old or older received HD therapy at St. Mary's Hospital in Kurume City, Fukuoka Prefecture, Japan. Of these, 59 were excluded. Patients with active psychiatric diseases, acute infections, or acute complications due to uremia were excluded because they were treated with antidepressant agents or other drugs. The other exclusion criteria were severe cognitive impairment, depression requiring major tranquilizers, and poor activity of daily living (ADL) ability. The final exclusion criterion was patients who underwent a short duration of HD treatment (i.e., \u0026lt; 6 months). Therefore, 114 HD patients were asked to participate in this study. Of these, 88 agreed to participate. Among them, 11 patients with incomplete data from questionnaires and biochemical tests were excluded from this study. Therefore, the study subjects were 77 HD patients (females, n\u0026thinsp;=\u0026thinsp;26, males, n\u0026thinsp;=\u0026thinsp;51) with a mean age of 62.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3 (SD) years. In addition to HD patients, 15 healthy volunteers with a mean age of 55.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 years agreed to donate blood samples to for the measurement of BDNF.\u003c/p\u003e\u003cp\u003eBiochemical and hematologic data were obtained prior to dialysis on December 1st and 2nd, 2006, respectively. Other clinical variables, including HD duration, primary renal disease, and comorbid diseases, were also documented.\u003c/p\u003e\u003cp\u003eThe body mass index (BMI) was calculated as the participant\u0026rsquo;s dry weight in kilograms divided by the square of their height in meters.\u003c/p\u003e\u003cp\u003eBlood pressure was measured before the dialysis procedure in the supine position after bed rest. Hypertension was defined as present if patients had a systolic blood pressure of \u0026ge;\u0026thinsp;140 mmHg or higher and/or a diastolic blood pressure of \u0026ge;\u0026thinsp;90 mmHg [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe blood tests included a complete blood count, serum chemistry, blood glucose, and hemoglobin A\u003csub\u003e1\u003c/sub\u003ec (HbA\u003csub\u003e1\u003c/sub\u003ec), which were examined in the St. Mary's Hospital laboratory. Serum BDNF levels were measured using a BDNF Emax Immunoassay System Kit (Promega, Madison, WI, USA).\u003c/p\u003e\u003cp\u003eThe cardiothoracic ratio (CTR) was calculated by dividing the cardiac diameter by the thoracic diameter on chest radiography (posterior-anterior view) before HD, whereas ischemic electrocardiogram (ECG) changes were defined as ST-depression detected by the standard twelve-lead ECG recorded before HD.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eEthics\u003c/h2\u003e\u003cp\u003e All participants received oral and written information about the experimental procedures before providing their written informed consent. This study was approved by the Ethical Committees of St. Mary's Hospital (0611-02, 24\u0026ndash;0702) and St. Mary's College (H18-012).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe mean serum BDNF level (\u0026plusmn;\u0026thinsp;SD) of HD patients was 12.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4. HD patients were divided into two groups according to their serum BDNF level (i.e., with a cutoff value of serum BDNF 12 ng/mL): (i) the high BDNF group (BDNF\u0026thinsp;\u0026gt;\u0026thinsp;12 ng/mL: n\u0026thinsp;=\u0026thinsp;39), and (ii) the low BDNF group (BDNF\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;12 ng/mL: n\u0026thinsp;=\u0026thinsp;38).\u003c/p\u003e\u003cp\u003eStatistical analyses were performed using Statistical Analysis System (SAS Institute, Cary, NC, USA). The Mann-Whitney U test or chi-square test was used to compare the high and low BDNF groups. An unconditional logistic model was applied to evaluate the odds ratios (ORs) and their 95% confidence intervals (CIs) with adjustments for several covariates. The CORR procedure was used to compute the Pearson and Spearman\u0026rsquo;s rank correlation coefficients. All p-values for the statistical tests were two-tailed, and a p-values of \u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the characteristics of the participants. The characteristics of the participants did not differ between the high and low BDNF groups.\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\u003e \u003cb\u003eCharacteristics of participants according to serum BDNF\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigh BDNF Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow BDNF group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMales, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (64.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (68.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of dialysis, years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.89\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetic nephropathy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (28.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (26.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiothoracic ratio, %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic findings on ECG, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (15.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystolic blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e126\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e129\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic blood pressure, mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (15.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebrovascular disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (7.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eContinuous data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and were examined using the Mann-Whitney U-test.\u003c/p\u003e\u003cp\u003eCategorical data are expressed as the number with percentage and were examined using the chi-square test.\u003c/p\u003e\u003cp\u003eBDNF, brain-derived neurotrophic factor; ECG, electrocardiogram\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the laboratory data and body mass index (BMI) of the participants based on their serum BDNF levels. Total cholesterol, LDL-cholesterol, body mass index, white blood cell count and platelet count were higher in the high BDNF group than in the low BDNF group.\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\u003eLaboratory data and body mass index of participants according to serum BDNF\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigher BDNF Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLower BDNF group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBDNF (ng/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e17.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cholesterol (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e156.4\u0026thinsp;\u0026plusmn;\u0026thinsp;34.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e138.3\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL-cholesterol (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e80.6\u0026thinsp;\u0026plusmn;\u0026thinsp;27.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e69.4\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.049\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglyceride (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e103.9\u0026thinsp;\u0026plusmn;\u0026thinsp;55.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e88.1\u0026thinsp;\u0026plusmn;\u0026thinsp;39.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.15\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDL-cholesterol (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e48.6\u0026thinsp;\u0026plusmn;\u0026thinsp;13.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e45.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdiponectin (ng /ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e15.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e14.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal protein (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood sugar (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e118.1\u0026thinsp;\u0026plusmn;\u0026thinsp;31.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e117.3\u0026thinsp;\u0026plusmn;\u0026thinsp;40.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1c (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e5.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e22.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite blood cell (x10\u003csup\u003e2\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e60.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e51.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRed blood cell (x10\u003csup\u003e4\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e333\u0026thinsp;\u0026plusmn;\u0026thinsp;48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e323\u0026thinsp;\u0026plusmn;\u0026thinsp;49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin (g/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e10.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets (x10\u003csup\u003e4\u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntact PTH (pg/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e297\u0026thinsp;\u0026plusmn;\u0026thinsp;299\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e286\u0026thinsp;\u0026plusmn;\u0026thinsp;445\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphate (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium (mg/dL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e9.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and were examined using the Mann-Whitney U-test.\u003c/p\u003e\u003cp\u003eBDNF, brain-derived neurotrophic factor; LDL, low-density lipoprotein; HDL, high-density lipoprotein; PTH, parathyroid hormone.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows age-and sex-adjusted ORs and 95% CIs for higher BDNF levels with respect to laboratory data and BMI. Higher serum cholesterol levels (\u0026gt;\u0026thinsp;147 mg/dl vs. \u0026le;147 mg/dl: OR\u0026thinsp;=\u0026thinsp;2.82, 95% CI\u0026thinsp;=\u0026thinsp;1.09\u0026ndash;7.32), white blood cell counts (\u0026gt;\u0026thinsp;5400/mm\u003csup\u003e3\u003c/sup\u003e vs. \u0026le;5400/mm\u003csup\u003e3\u003c/sup\u003e; OR\u0026thinsp;=\u0026thinsp;2.74, 95% CI\u0026thinsp;=\u0026thinsp;1.08\u0026ndash;6.98) and platelet counts (\u0026gt;\u0026thinsp;160,000/mm\u003csup\u003e3\u003c/sup\u003e vs. \u0026le;160,000/mm\u003csup\u003e3\u003c/sup\u003e; OR\u0026thinsp;=\u0026thinsp;36.90, 95% CI\u0026thinsp;=\u0026thinsp;10.10-134.83) were associated with an increased risk of higher BDNF even after adjusting for age and sex, whereas higher BMI (\u0026gt;\u0026thinsp;21 kg/m\u003csup\u003e2\u003c/sup\u003e vs. \u0026le;21 kg/m\u003csup\u003e2\u003c/sup\u003e; OR\u0026thinsp;=\u0026thinsp;2.50, 95% CI\u0026thinsp;=\u0026thinsp;0.97\u0026ndash;6.46) tended to be associated with higher BDNF levels, but failed to reach statistical significance.\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\u003eFactors related to high serum BDNF and their age- and sex-adjusted odds ratios and 95% confidence intervals\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=\"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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigh BDNF Group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLow BDNF group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;38)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAge and sex-adjusted\u003c/p\u003e\u003cp\u003eodds ratio\u003c/p\u003e\u003cp\u003e(95% confidence intervals)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAge and sex- adjusted\u003c/p\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;147 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (56.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (31.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.82 (1.09\u0026ndash;7.32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL\u0026ndash;cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;75 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (46.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13 (34.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.60 (0.63\u0026ndash;4.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite blood cell count\u0026thinsp;\u0026gt;\u0026thinsp;5400/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24 (61.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (36.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.74 (1.08\u0026ndash;6.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet count\u0026thinsp;\u0026gt;\u0026thinsp;160,000/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33 (84.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (13.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e36.90 (10.10\u0026ndash;134.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody mass index\u0026thinsp;\u0026gt;\u0026thinsp;21 kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (53.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (31.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.50 (0.97\u0026ndash;6.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData are expressed as the number with percentage༎\u003c/p\u003e\u003cp\u003eBDNF, brain-derived neurotrophic factor; LDL, low-density lipoprotein.\u003c/p\u003e\u003cp\u003eEven after adjusting for age, sex and all factors in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, a higher platelet count (\u0026gt;\u0026thinsp;160,000/mm\u003csup\u003e3\u003c/sup\u003e vs. \u0026le; 160,000/mm\u003csup\u003e3\u003c/sup\u003e; OR\u0026thinsp;=\u0026thinsp;60.89, 95% CI\u0026thinsp;=\u0026thinsp;10.38-357.29) showed a significantly increased OR (not shown in the table).\u003c/p\u003e\u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, a significantly positive relationship was observed between platelet count and serum BDNF levels in the present study (Spearman rank correlation: r\u0026thinsp;=\u0026thinsp;0.76, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBDNF has been suggested to play a role in glucose and lipid metabolism and energy homeostasis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In the present study, total cholesterol, LDL-cholesterol, and body mass index were higher in the high BDNF group (BDNF\u0026thinsp;\u0026gt;\u0026thinsp;12 ng/mL) than in the low BDNF group (BDNF\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;12 ng/mL). The results of the present study (mean age 62.8 years) are consistent with the results of the Baltimore Longitudinal Study of Aging (mean age: males, 71.9 years; females, 70.3 years) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. They reported that BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol in females whereas BDNF was positively correlated with diastolic blood pressure, and triglycerides in males [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eKrabbe et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] reported an inverse association between plasma BDNF and fasting plasma glucose levels. In their study, plasma levels of BDNF were lower in patients with type 2 DM than in those without DM, and were lower in obese participants than in non-obese participants [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In contrast, Suwa et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] reported that serum BDNF levels were higher in patients with early-stage DM than in healthy subjects. In their study [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], serum BDNF levels were positively associated with BMI, body fat percentage, triglyceride level, fasting blood glucose level and insulin resistance score among patients with early-stage DM.\u003c/p\u003e\u003cp\u003eIn the present study, the proportions of diabetic nephropathy, blood sugar and hemoglobin A1c did not differ between the high- and low- BDNF groups, which may be partly due to the small number of diabetic patients in the present study (i.e., 11 of 39 HD patients [28.2%] in the high BDNF group, and 10 out of 38 HD patients [26.3%] in the low BDNF group). We excluded the following patients: (1) patients with active psychiatric diseases, infections, or acute complications due to uremia; (2) patients with severe cognitive impairment, depression requiring major tranquilizers, or poor ADL ability; and (3) patients who underwent short-duration HD treatment (i.e., \u0026lt;\u0026thinsp;6 months). Therefore, further studies with larger numbers of HD patients are recommended to explain the findings of the present study.\u003c/p\u003e\u003cp\u003eHypertension (including prehypertension), which is major risk factors for coronary artery disease (CAD) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and left ventricular hypertrophy (LVH), are highly common in patients with ESRD [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Hypertension and anemia are risk factors for LVH [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and LVH increases the risk of mortality in HD patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Therefore, secondary prevention (i.e., early detection and treatment) of treatable risk factors is important to reduce the risk of CVD.\u003c/p\u003e\u003cp\u003eIn the present study, however, the degree of hypertension (i.e., systolic blood pressure, diastolic blood pressure), degree of anemia (i.e., red blood cell counts or hemoglobin), and CTR did not differ between the higher and lower groups. In contrast, the average CTR was \u0026gt;\u0026thinsp;50% in both groups. HD-induced stress (e.g., high arteriovenous blood flow, hemodynamic stress due to rapid volume contraction, and a significant amount of fluid weight between HD sessions) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] may partly explain the increase in CTR.\u003c/p\u003e\u003cp\u003eAmadio et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported that plasma BDNF levels in patients with CAD were lower than those in healthy subjects. Furthermore, plasma BDNF was lower in patients with stable angina than in patients with acute myocardial infarction CAD patients in their study [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In addition, Kaess et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] reported that serum BDNF was inversely associated with the cardiovascular disease risk in the community in a cohort study (i.e., the Framingham Heart Study). In the present study, the proportion of HD patients with CAD was two times that in the low BDNF group than in the high BDNF group (15.8% vs. 7.7%), however this difference was not statistically significant because of the small number of participants in the present study.\u003c/p\u003e\u003cp\u003ePlatelet counts in HD patients may decrease during HD because platelet counts in patients on continuous ambulatory peritoneal dialysis (CAPD) are closer to the normal range [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. There are several possible explanations for a decrease in the platelet count. First, heparin, which is used as an anticoagulant for HD patients, is known to promote platelet agglutination [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Exposure to heparin tends to cause platelets to self-aggregate [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Second, dialyzer hypersensitivity symptoms are infrequently associated with a reduction in platelet counts, and some activation and aggregation of platelets during dialysis may be due not only to the exposure of blood to the dialyzer but also to the exposure of blood to the roller pump segment of the dialysis tubing or to microbubbles [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the present study, the platelet count in the high BDNF group was higher than the in the low BDNF group. In addition, a positive relationship was observed between platelet count and serum BDNF level in the present study (Spearman rank correlation: r\u0026thinsp;=\u0026thinsp;0.76, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), which may be partly explained as follows:\u003c/p\u003e\u003cp\u003esince platelets bind, store, and release BDNF upon activation at the site of traumatic injury to facilitate tissue repair [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], platelets may release BDNF upon activation of injured blood cells during the dialysis procedure. Therefore, there may be a positive relationship between serum BDNF levels and platelet counts in patients undergoing HD.\u003c/p\u003e\u003cp\u003eHD patients are at a high risk of contracting blood-borne infections such as hepatitis B virus [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] and hepatitis C virus [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Although isolation of carriers and screening of blood donors may be effective in the prevention of blood-borne viral infections among HD patients [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], hepatitis B and C remain prevalent in dialysis patients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Thrombocytopenia is common in patients with chronic liver diseases [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], which may be partly explained by the fact that chronic liver disease (hepatitis B, hepatitis C, and nonalcoholic fatty liver disease) is prevalent in dialysis patients [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Iwamoto et al. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] reported a negative association between platelet counts and years of HD among Japanese HD patients.\u003c/p\u003e\u003cp\u003eThe present study had several limitations. First, it was a cross-sectional study. Therefore, we could not determine whether factors related to higher serum BDNF levels were the cause or result of higher serum BDNF. Second, the number of participants in the present study was not sufficient to evaluate the factors in a multivariate analysis. Third, the participants in the present study were HD patients. Therefore, the findings of the present study were influenced not only by the uremic condition itself but also by the intermittent dialysis procedure (3 days a week). Fourth, echocardiographic examinations were not performed in this study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, serum total cholesterol level, white blood cell count and platelet count were positively associated with serum BDNF levels even after controlling for age and sex. Furthermore, platelet count remained a significant risk factor for increased BDNF levels even after controlling for age, sex, total serum cholesterol level, and white blood cell count.\u003c/p\u003e\u003cp\u003eSince platelets are suggested to play important roles not only in the initiation but also in the progression of atherosclerosis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], further studies are needed to clarify the role of serum BDNF in HD patients.\u003c/p\u003e\u003cp\u003eA part of this study was presented at the 58th Annual Meeting of the Japanese Society for Dialysis Therapy in Fukuoka in 2013.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cdfn\u003eBDNF:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eBrain-derived neurotrophic factor\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eHD:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eHemodialysis\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eCVD:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eCardiovascular disease\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eLDL:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eLow-density lipoproteins\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eDM:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eDiabetes mellitus\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eADL:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eActivities of daily living\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eBMI:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eBody mass index\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eCVD:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eCardiovascular disease\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eHbA1c:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eHemoglobin A\u003csub\u003e1\u003c/sub\u003ec\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eECG:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eElectrocardiogram\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eORs:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eOdds ratios\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eLVH:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eLeft ventricular hypertrophy\u003cdfn\u003e\u0026nbsp;\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eCAD:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eCoronary artery disease\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eCAPD:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eContinuous ambulatory peritoneal dialysis\u003c/p\u003e\n\u003cp\u003e\u003cdfn\u003eCTR:\u003c/dfn\u003e\u003c/p\u003e\n\u003cp\u003eCardiothoracic ratio\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFounding\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eInformed consent was obtained from all the participants. This study was approved by the Ethical Committees of St. Mary\u0026apos;s Hospital (0611-02, 24\u0026ndash;0702) and St. Mary\u0026apos;s College (H18-012).\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eH.H., R.N., M.W., and K.T. contributed to the conception and design of the study and contributed to the analysis and interpretation of the data. H.H., R.N., M.W., K.T., K.T., T.N., M.K, and T.K. contributed to the critical reading of the article for important intellectual content, final approval of the article, and drafting of the article.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThis study was partly supported by St. Mary\u0026rsquo;s Hospital, and St. Mary\u0026apos;s College.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHanafusa N, Abe M, Joki N, Hoshino J, Taniguchi M, Kikuchi K, et al. 2022 annual dialysis data report, JSDT renal data registry. Nihon Toseki Igakukai Zasshi (J Jpn Soc Dial Ther) 2023; 56(12): 473-536. (in Japanese)\u003c/li\u003e\n\u003cli\u003eMasakane I, Nakai S, Ogata S, Kimata N, Hanafusa N, Hamano T, et al. An Overview of Regular Dialysis Treatment in Japan (As of 31 December 2013). Therapeutic Apheresis and Dialysis 2015; 19(6):540\u0026ndash;574.\u003c/li\u003e\n\u003cli\u003ePrichard SS. Impact of Dyslipidemia in End-Stage Renal Disease. J Am Soc Nephrol 2003; 14: S315\u0026ndash;S320. doi: 10.1097/01.asn.0000081698.10331.83.\u003c/li\u003e\n\u003cli\u003eCozzolino M, Mangano M, Stucchi A, Ciceri P, Conte F, Galassi A. Cardiovascular disease in dialysis patients. Nephrol Dial Transplant 2018; 33: iii28-iii34 doi:10.1093/ndt/gfy174.\u003c/li\u003e\n\u003cli\u003ePrichard SS. Coronary artery disease in end-stage renal disease: risk factors and treatment strategies. Nihon Toseki Igakukai Zasshi (J Jpn Soc Dial Ther) 2000;33(3):159-164. DOI: https://doi.org/10.4009/jsdt.33.159\u003c/li\u003e\n\u003cli\u003eThoenen H. Neurotrophins and neuronal plasticity. Science 1995; 270:593-598. doi: 10.1126/science.270.5236.593.\u003c/li\u003e\n\u003cli\u003eMa YL, Wang HL, Wu HC, Wei CL, Lee EHY. Brain-derived neurotrophic factor antisense oligonucleotide impairs memory retention and inhibits long-term potentiation in rats. Neuroscience 1998; 82:957-967. doi: 10.1016/s0306-4522(97)00325-4.\u003c/li\u003e\n\u003cli\u003eTsuchida A, Nonomura T, Nakagawa T, Itakura Y, Ono-Kishino M, Yamanaka M, et al. Brain-derived neurotrophic factor ameliorates lipid metabolism in diabetic mice. Diabetes Obes Metab 2002; 4(4):262-269. doi: 10.1046/j.1463-1326.2002.00206.x.\u003c/li\u003e\n\u003cli\u003eSuwa M, Kishimoto H, Nofuji Y, Nakano H, Sasaki H, Radak K, et al. Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabolism 2006; 55(7): 852-857. \u003c/li\u003e\n\u003cli\u003eFujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 2002; 87(4): 728-734.\u003c/li\u003e\n\u003cli\u003eGolden E, Emiliano A, Maudsley S, Windham BG, Carlson OD, Egan JM, et al. Circulating Brain-Derived Neurotrophic Factor and Indices of Metabolic and Cardiovascular Health: Data from the Baltimore Longitudinal Study of Aging. PLoS One. 2010 Apr 9;5(4): e10099. doi: 10.1371/journal.pone.0010099.\u003c/li\u003e\n\u003cli\u003eZoladz JA, Śmigielski M, Majerczak J, Nowak ŁR, Zapart-Bukowska J, Smoleński O. Hemodialysis decreases serum brain-derived neurotrophic factor concentration in humans. Neurochem Res. 2012; 37(12):2715-2724.\u003c/li\u003e\n\u003cli\u003eNishichi R, Higashi H, Washio M, Todo K, Kumagai S. Association between mental health and serum brain-derived neurotrophic factor in hemodialysis patients. Intern Med J 2011; 18 (2): 114 -116.\u003c/li\u003e\n\u003cli\u003eThe Japanese society of hypertension. Guidelines for the management of hypertension 2019. Tokyo: Life Science Publishing Co., LTd, 2019. (in Japanese)\u003c/li\u003e\n\u003cli\u003eKrabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, et al. et al. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007; 50(2):431-4.\u003c/li\u003e\n\u003cli\u003eHata J, Kiyohara Y. Epidemiology of stroke and coronary artery disease in Asia. Circ J. 2013;77(8): 1923-32. doi: 10.1253/circj. CJ-13-0786.\u003c/li\u003e\n\u003cli\u003eWashio M, Tokunaga S, Yoshimatsu K, Kodama H, Liu Y, Sasazuki S, et al. Role of prehypertension in the development of coronary atherosclerosis in Japan. J Epidemiol 2004;14(2):57-62. doi:10.2188/jea.14.57.\u003c/li\u003e\n\u003cli\u003eWashio M, Okuda S, Mizoue T, Kiyama S, Ando T, Sanai T, et al. Risk factors for left ventricular hypertrophy in chronic hemodialysis patients. Clin Nephrol 1997; 47(6): 362-366.\u003c/li\u003e\n\u003cli\u003eParfrey PS, Harnett JD, Griffiths SM, Taylor R, Hand J, King A, et al. The clinical course of left ventricular hypertrophy in dialysis patients. Nephron 1990; 55(2):114-120. doi:10.1159/000185937.\u003c/li\u003e\n\u003cli\u003eAhmadmehrabi S, Tang WHW. Hemodialysis-induced cardiovascular disease. Semin Dial 2018;31(3): 258-267.doi:10.1111/sdi.12694\u003c/li\u003e\n\u003cli\u003eAmadio P, Cosentino N, Eligini S, Barbieri S, Tedesco CC, Leonardo S, et al. Potential Relation between Plasma BDNF Levels and Human Coronary Plaque Morphology. Diagnostics 2021, 11, 1010. https://doi.org/10.3390\u003cins cite=\"mailto:Editor\" datetime=\"2025-07-07T14:11\"\u003e/\u003c/ins\u003e\u003cdel cite=\"mailto:Editor\" datetime=\"2025-07-07T14:11\"\u003e/ \u003c/del\u003ediagnostics11061010\u003c/li\u003e\n\u003cli\u003eKaess BM, Preis SR, Lieb W, Beiser AS, Yang Q, Chen TC, et al. Circulating brain-derived neurotropic factor concentrations and the risk of cardiovascular disease in the community. J Am Heart Assoc 2015; 4(3): e001544. doi: 10.1161/JAHA.114.001544.\u003c/li\u003e\n\u003cli\u003eDaugirdas JT, Bernardo AA. Hemodialysis effect on platelet count and function and hemodialysis-associated thrombocytopenia. Kidney International 2012; 82: 147\u0026ndash;157.\u003cdel cite=\"mailto:Editor%202\" datetime=\"2025-07-07T13:49\"\u003e \u003c/del\u003e\u003cdel cite=\"mailto:Editor%202\" datetime=\"2025-07-07T13:49\"\u003e \u003c/del\u003e\u003c/li\u003e\n\u003cli\u003eWashio M, Tokui N, Okuda S, Nagashima A, Sanai T, Hirakata H, et al. Hepatitis B surface antigen and antibody among chronic hemodialysis patients in Fukuoka, Japan: a high risk for becoming Hepatitis B virus carriers. J Epidemiol 1994; 4: 99-102. \u003c/li\u003e\n\u003cli\u003eSwift O, Sharma S, Ramanarayanan S, Umar H, Laws KR, Vilar E, et al. Prevalence and outcomes of chronic liver disease in patients receiving dialysis: systematic review and meta-analysis. Clin Kidney J 2021; 15(4): 747-757.\u003c/li\u003e\n\u003cli\u003eWashio M, Ikeda M, Okuda S, Nakamura S, Fukumitsu T, Mizoue T, et al. Hepatitis C virus antibody in patients on chronic hemodialysis in Fukuoka, Japan. J Epidemiol 1991; 1: 31-36. \u003c/li\u003e\n\u003cli\u003eWashio M. Blood-borne viral infection in hemodialysis units: special reference to hepatitis B virus, hepatitis C virus and human T-lymphotropic virus type 1. Nihon Koshu Eisei Zasshi (Japanese Journal of Public Health). 1998; 45(10):960-967. (in Japanese)\u003c/li\u003e\n\u003cli\u003ePeck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2017 ;37(6):778-793.\u003c/li\u003e\n\u003cli\u003eIwamoto Y, Ando M, Tsuchiya K, Nihei H. Clinical analysis of thrombocytopenia in chronic dialysis patients. Jpn J Nephrol 1999; 41: 712-718. (in Japanese)\u003c/li\u003e\n\u003cli\u003ePalomo I, Toro C, Alarc\u0026oacute;n M. The role of platelets in the pathophysiology of atherosclerosis (Review). Mol Med Rep. 2008;1(2):179-84.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Brain-derived neurotrophic factor, Cardiovascular disease, Chronic renal failure, Hemodialysis","lastPublishedDoi":"10.21203/rs.3.rs-7827190/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7827190/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBrain-derived neurotrophic factor (BDNF) may play a role in glucose and lipid metabolism as well as mental health. We previously reported a negative association between BDNF levels and mental health in hemodialysis (HD) patients. Cardiovascular disease (CVD) is a common cause of death in patients undergoing HD. However, we have not yet evaluated the associations between serum BDNF levels and risk factors for CVD in HD patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA cross-sectional study was conducted to evaluate the factors associated with serum BDNF levels in HD patients without active mental disorders. Seventy-seven HD patients were divided into two groups according to their serum BDNF levels: (i) the high BDNF group (BDNF\u0026gt;12 ng/mL: n=39), and (ii) the low BDNF group (BDNF \u003cu\u003e\u0026lt;\u003c/u\u003e 12 ng/mL: n=38). Demographic and laboratory parameters were compared between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe values for total cholesterol, low-density lipoprotein (LDL) - cholesterol, body mass index, white blood cell count and platelet count were higher in the high BDNF group than in the low BDNF group.\u003c/p\u003e\n\u003cp\u003eHigher serum total cholesterol levels, white blood cell counts and platelet counts were associated with an increased risk of higher serum BDNF levels even after controlling for age and sex. Furthermore, a higher platelet count remained a significant risk factor for higher BDNF levels even after controlling for higher total serum cholesterol levels and white blood cell counts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSince platelets are suggested to play important roles not only in the initiation but also in the progression of atherosclerosis, BDNF might play a role in the development of atherosclerosis in patients on HD.\u003c/p\u003e","manuscriptTitle":"Factors related to serum brain-derived neurotrophic factor level in chronic hemodialysis patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 07:45:29","doi":"10.21203/rs.3.rs-7827190/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-01T16:52:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-06T23:11:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T01:43:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197714423886129334275488019844785360752","date":"2025-11-28T15:02:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27742719552341424533087092108670344146","date":"2025-11-27T01:07:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-26T02:06:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"272462579273161846373262563736873459334","date":"2025-11-26T01:40:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255379316636523660377573604535554936381","date":"2025-11-23T23:36:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-23T23:35:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-20T10:34:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-20T02:30:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Internal Medicine","date":"2025-10-10T12:46:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-internal-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Internal Medicine](https://ejim.springeropen.com/)","snPcode":"43162","submissionUrl":"https://submission.springernature.com/new-submission/43162/3","title":"The Egyptian Journal of Internal Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38c4dfd5-5bc7-4154-b944-bdd71c719260","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T10:12:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 07:45:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7827190","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7827190","identity":"rs-7827190","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}