Non-diabetic Hemodialysis Patients Research Articles

Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: a randomized double-blind study.

Polyphenols contained in natural sources such as grapes, have been considered pharmacological agents to combat oxidative stress and inflammation, common features in Chronic Kidney Disease patients. To evaluate the effects of grape powder supplementation on inflammatory and antioxidant biomarkers in hemodialysis (HD) patients. The double-blind placebo-controlled randomized clinical trial evaluated non-diabetic HD patients that received grape powder (500 mg of polyphenols/day) (n = 16, 9 men, 53.0 ± 9.8 years of age, 111.6 ± 58.2 HD months) or placebo (n = 16, 9 men, 52.7 ± 13.7 years of age, 110.4 ± 93.1 HD months) for five weeks. The glutathione peroxidase (GSH-Px) activity and C-reactive protein (CRP) levels were evaluated by ELISA method. After the intervention period, the patients receiving grape powder showed an increase in the GSH-Px activity (16.5 (41.0) to 42.0 (43.3) nmol/min/ml) (p < 0.05) and they did not have the CRP levels increased as seen in placebo group (2.6 (0.28) to 2.8 (0.23 mg/L) (p < 0.05). The use of grape powder as phenolic source could play an important role as an antioxidant and anti-inflammatory agent in non-diabetic HD patients.

Correlation of Interleukin-17-Producing Effector Memory T Cells and CD4+CD25+Foxp3 Regulatory T Cells with the Phosphate Levels in Chronic Hemodialysis Patients

Background and Objectives. Hyperparathyroidism and hyperphosphatemia contribute to the inflammatory effects in chronic hemodialysis (HD) patients. Interleukin-17-producing CD4 + effector memory T (Th17) cells and CD4+CD25+Foxp3 regulatory T (Treg) cells both play critical roles in immune activation and inflammation. We investigated the relationship between the Treg and Th17 cells and the phosphate level in chronic HD patients. Methods. 105 patients aged ≥35 years on chronic HD over 3 months were enrolled. The peripheral blood mononuclear cells were collected, cultured, and stimulated by phytohemagglutinin-L, phorbol myristate acetate, and ionomycin at different time points for T cell differentiation. Results. The T cell differentiation was as follows: Th17 cells (mean ± standard deviation (SD): 25.61% ± 10.2%) and Treg cells (8.45% ± 4.3%). The Th17 cell differentiation was positively correlated with the phosphate and albumin levels and negatively correlated with age. The Treg cell differentiation was negatively correlated with albumin level and age. In the nondiabetes group (n = 53), the Th17 cell differentiation was predominantly correlated with the phosphate and iPTH (intact parathyroid hormone) levels as well as the dialysis vintage. Conclusion. Higher phosphate and iPTH levels and longer dialysis duration may increase Th17 cell differentiation, especially in the nondiabetic chronic HD patients.

Impaired postprandial response of the insulin-like growth factor system in maintenance haemodialysis

Patients on maintenance haemodialysis (HD) have reduced circulating free and bioactive insulin-like growth factor I (IGF-I) due to increased IGF-binding proteins (IGFBPs). This study investigated the postprandial response of the IGF system in HD patients compared with matched healthy subjects. In a crossover study, twelve nondiabetic HD patients were assigned in a random order to three 10-h study days: (1) a non-HD day with one meal served at baseline (NHDM1), (2) an HD day with one meal served during HD (HDM1) and (3) an HD day with two meals served during and after HD, respectively (HDM2). Twelve healthy controls conducted session 1. After the baseline meal, insulin concentrations changed similarly in HD patients and controls, whereas hyperglycaemia was more prolonged in HD patients (P < 0·001). Postprandial IGFBP-1 showed greater reductions from baseline in controls (-76% [-81; -70%], mean [95% confidence intervals], P < 0·001) than in patients on non-HD days (-45% [-57; -30%], P < 0·001). In the latter group, the response was even more attenuated during HD (-22% [-38; -1%] and -24% [-40; -4%], P ≤ 0·041). After the second meal on HDM2 days, IGFBP-1 further decreased (-50% [-61; -37%], P < 0·001), whereas IGFBP-1 returned to baseline levels on the other study days. Consistently, at the end of the study days, bioactive IGF-I was significantly above baseline only on HDM2 days (+22% [+5; +43%], P = 0·012). HD patients were unable to suppress IGFBP-1 to the same extent as healthy controls, which may increase the risk of protein-energy wasting in maintenance HD. A second meal after HD, however, effectively suppressed IGFBP-1 and increased bioactive IGF-I.

Carotid intima-media thickness and left ventricular hypertrophy in hemodialysis patients.

Introduction: Two principal findings of cardiovascular disease in end-stage renal disease patients undergoing regular hemodialysis are left ventricular hypertrophy (LVH) and arterial disease due to rapidly progressive atherosclerotic vascular disease that can be characterized by an enlargement and hypertrophy of arteries (intima-media complex thickening; IMT).Objectives: In this study, we sought to evaluate the relationship between left ventricular hypertrophy with intima-media complex thickening in end-stage renal disease patients undergoing regular hemodialysis. Patients and Methods: Sixty-one patients with end-stage renal disease (ESRD) who were undergoing regular and maintenance hemodialysis treatment (F=23, M=38) were studied. The subjects consisted of 50 non-diabetic hemodialysis patients (F=20, M=30) and 11 diabetic hemodialysis patients (F=3, M=8). For all the subjects, echocardiography and carotid intima-media thickness measuring by B-mode ultrasonography were performed. Results: In this study, there was a positive correlation between stages of LVH with duration of hemodialysis treatment, stages of hypertension (HTN), and with carotid-IMT. A positive correlation was also seen between stages of LVH and presence of chest pain, and more thickening of the intima-media complex was seen in the diabetic group. Diabetes mellitus was associated with the presence of chest pain, as was positive correlation between stages of HTN with IMT, and a reverse correlation was observed between IMT with the percent of cardiac ejection fraction. Conclusion: Prevalence of thickening in intima-media complex is more evident in hemodialysis subjects with LVH. When there is LVH, IMT is similar in severity to the LVH.

Ankle‐Brachial Index and Cardiovascular Mortality in Nondiabetic Hemodialysis Patients

Atherosclerosis is a leading cause of morbidity and mortality in hemodialysis (HD) patients. Low (<0.90) and high (>1.40) ankle-brachial index (ABI) is known as a non-invasive diagnostic marker for generalized atherosclerosis associated with higher cardiovascular (CV) mortality in the general population. Less is known about associations between ABI and CV mortality in HD patients. The aim of our study was to determine the impact of the ABI on CV mortality in nondiabetic HD patients. Fifty-two nondiabetic HD patients (mean age 59 years, range 22 - 76 years) were enrolled in our study. Twenty-three (44%) were women and 29 (56%) men. The ABI was determined using an automated, non-invasive, waveform analysis device. All patients were divided according to the ABI into three groups: low ABI (<0.9), normal ABI (0.9-1.4) and high ABI (>1.4). The presence of arterial hypertension and smoking was established. Serum cholesterol (HDL and LDL) and triglycerides were measured by routine laboratory methods. Survival rates were analyzed using Kaplan-Meier survival curves. The Cox regression model was used to assess the influence of the ABI on CV outcomes. The model was adjusted for age, arterial hypertension, smoking, cholesterol and triglycerides. Mean ABI value was 1.2 ± 0.3 (range 0.2-2.2). Patients were observed from the date of the ABI measurement until their death or maximally up to 1620 days. Kaplan-Meier survival analysis showed that the risk for CV death was higher for HD patients with low and high ABI compared to normal ABI (log rank test: P < 0.006; P < 0.0001). In the adjusted Cox multivariable regression model low and high ABI (P < 0.011; P < 0.003) remained predictors of mortality in our patients. The results indicate a U-shaped association between the ABI and CV mortality in nondiabetic HD patients and showed that low and high ABI were directly associated with higher mortality of our patients.

Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study

BackgroundA marked reduction in serum levels of bioactive insulin-like growth factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a 4-h HD session. The aim of the present study was to investigate the beneficial effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory biomarkers.MethodsIn a randomized cross-over study, 11 non-diabetic HD patients received a standardised HD session with either: 1) no treatment, 2) glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10% glucose added 30 IU NovoRapid® per litre, 2.5 mL/kg/h). Each experiment consisted of three periods: pre-HD (−120 to 0 min), HD (0 to 240 min), and post-HD (240 to 360 min). A meal was served at baseline (−120 min); infusions were administered from baseline to 240 min. The primary outcome was change in bioactive IGF-I during the experiment. Secondary outcomes were changes in high-sensitivity C-reactive protein, interleukin-1β, interleukin-6, and tumor necrosis factor α. Comparisons were performed using mixed-model analysis of variance for repeated measures.ResultsFrom baseline to the end of study, no significant differences were observed in the changes in either serum bioactive IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min (95% confidence interval (CI), 9 to 31%; p < 0.001), whereas total IGF-I levels rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min (95% CI, 2 to 9%; p = 0.004). A significant difference was observed in the changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p = 0.008), but differences were only significant in the post-HD period. From baseline to the end of HD, no significant difference was observed in the changes in serum IGFBP-1 levels between study days, and in this time period overall serum IGFBP-1 levels were below baseline at all time points with a maximum decrease of 51% at 180 min (95% CI, 45 to 57%; p < 0.001). None of the investigated inflammatory biomarkers showed any differences in the changes over time between study days.ConclusionsPostprandial insulin secretion stimulated the IGF-system during HD with no further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia during HD had no effect on biomarkers of inflammation.Trial registrationClinicalTrials.gov registry: NCT01209403

Evaluation of choroidal and retinal thickness measurements using optical coherence tomography in non-diabetic haemodialysis patients

The aim of this study is to evaluate the effects of haemodialysis with a high ultrafiltration rate on the choroidal and retinal thickness of non-diabetic end-stage chronic renal failure (CRF) patients using optical coherence tomography (OCT). Twenty-one eyes of 21 male CRF patients aged between 46 and 80 years were included in this prospective study. Retinal and choroidal thicknesses of the patients were measured using high-resolution OCT line scans with the activated enhanced depth imaging mode before and shortly after haemodialysis. Retinal and choroidal thickness measurements were taken at the fovea and at two points that were 1,500 μm nasal and temporal to the fovea. The relationships between the haemodynamic changes, intraocular pressure (IOP) and central corneal thickness (CCT) were also evaluated. The mean choroidal thicknesses before haemodialysis at the subfoveal, temporal and nasal locations were 232.81 ± 71.92, 212.43 ± 70.50 and 182.14 ± 68.88 μm, respectively. The mean choroidal thicknesses after haemodialysis at the subfoveal, temporal and nasal locations were 210.90 ± 65.53, 195.38 ± 66.48 and 165.19 ± 66.73 μm, respectively. There were significant differences between the choroidal thicknesses before and after haemodialysis (p < 0.001 for all). The mean retinal thicknesses before haemodialysis at the foveal, temporal and nasal locations were 215.86 ± 41.06, 308.86 ± 37.73 and 338.00 ± 33.32 μm, respectively. The mean retinal thicknesses after haemodialysis at the foveal, temporal and nasal locations were 216.90 ± 39.70, 313.86 ± 32.89 and 335.29 ± 36.85 μm, respectively. There was no significant difference between the retinal thicknesses before and after haemodialysis (p > 0.05 for all). The mean CCT decreased insignificantly from 550.48 ± 17.46 to 548.10 ± 21.12 μm (p = 0.411). The mean IOP decreased significantly from 14.09 ± 2.58 to 12.54 ± 2.23 mmHg (p = 0.003), which did not correlate with the CCT [r = (-)0.134, p = 0.562]. Haemodialysis with a high ultrafiltration volume did not alter the retinal thickness but caused a significant choroidal thinning and an IOP decrease in non-diabetic end-stage CRF patients.

Long-term effects of arteriovenous fistula on cardiac structure and function in non-diabetic hemodialysis patients

To evaluate the long-term effects of arteriovenous fistula (AVF) on heamodynamic changes and cardiac structure and function in non-diabetic hemodialysis patients. Data were collected from 50 non-diabetic hemodialysis patients (aged 18 to 60 years) who had used AVF as the vascular access. AVF flow (Qa), stoke volume (SV), cardiac output (CO), cardiac index (CI), central blood volume (CBV) and peripheral vascular resistance (PR) were measured using the ultrasound dilution technique. Echocardiography was performed in the second day after hemodialysis sessions to evaluate the influence of AVF on the cardiac structure and function. The cubic polynomial regression model best fit the relationships of Qa with SV, CO, and CI. CO and CI significantly increased and PR reduced when the Qa of AVF was more than 2.0 L/min(all P<0.05), and no statistical difference of CO, CI and PR in groups of Qa between 0.6-2.0 L/min and less than 0.6 L/min(all P>0.05). In different Qa groups, the grades of cardiac function (based on New York Heart Association classification) showed significant difference, among which the cardiac failure was significantly common when Qa >2.0 L/min(both P<0.05). Echocardiography showed the left atrium dimension, thickness of posterior wall and interventricular seprum of left ventricle, left ventricular end-systolic dimension (LVESD) and end-diastolic dimension (LVEDD), venae cava inferior, and pulmonary artery systolic pressure gradually increased when Qa increased, while the ejection fraction and fractional shortening reduced(all P<0.05). Notably, the changes of LVESD, LVEDD, and venae cava inferior with different Qa were statistically significant(all P<0.05). Long-term AVF remarkably affects the cardiovascular dynamics of non-diabetic hemodialysis patients. A cubic polynomial regression model best fits the relationship of AVF Qa with SV, CO, and CI. The cardiac adaptic changes after long-term AVF include the enlargement of left ventricle and the thickening of ventricular wall. The risk of cardiac failure significantly increases when the Qa of AVF is more than 2.0 L/min with much higher CO and lower PR.

Relationship between serum parathyroid hormone levels and lipid profile in non-diabetic hemodialysis patients.

Elevated levels of intact parathyroid hormone (iPTH) may play an important role in the pathogenesis of the dyslipidemia in hemodialysis (HD) patients, but the underlying mechanisms are not clearly defined. In this cross-sectional study, we examined the effects of iPTH on dyslipidemia among HD patients by analyzing the data of 51 patients (18 males and 33 females) with combined mean age 51.7 ± 18.3 years (range 22-85 years) who were on HD between April 2009 and April 2010, in the dialysis center of Imam Khomeini Hospital Complex in Iran. On enrollment, we measured lipid profile, apoprotein (apo) A, apo B, alkaline phosphatase, calcium and phosphorus and also recorded the duration that they were on HD, and evaluated the correlation of these with iPTH level using Spearman's rank analysis. The mean duration on HD was 7.07 ± 6.53 years. Except for high-density lipoprotein, there were no changes in the lipid parameters in our HD patients. We also compared lipid profile among subjects, classifying them according to their iPTH levels. There was no correlation between serum lipids and iPTH levels in these groups. A significant positive correlation was found between iPTH and alkaline phosphatase( ALP) (r = 0.333, P = 0.017) between iPTH and HD duration (r = 0.408, P = 0.003), whereas there was a significant negative correlation between iPTH and Ca (r = -0.294, P = 0.037) between iPTH and apo B (r = -0.431, P = 0.002) and between iPTH and Body Mass Index (r = -0.362, P = 0.009). In conclusion, no significant relationship between iPTH and lipids was found in the studied HD patients. These findings suggest that iPTH most probably does not play a significant role in the dyslipidemia of renal failure.

Insulin Resistance and Left Ventricular Mass in Non-Diabetic Hemodialysis Patients

BackgroundInsulin resistance (IR) is frequently recognized in patients with uremia, and it is thought that IR has a basic role in the pathogenesis of cardiovascular disease. ObjectiveTo evaluate the effect of IR on cardiovascular risk in non-diabetic patients receiving hemodialysis (HD). MethodsWe performed a cross-sectional observational study that comprised 186 non-diabetic patients receiving HD (95 men; mean [SD] age, 46.4 [10.8] years; age range, 35–60 years) who had been receiving HD for 7.3 (3.5) years. Demographic variables and laboratory values were recorded. Insulin resistance was determined using the Homeostatic Model Assessment (HOMA), and the left ventricular mass index (LVMI) was calculated via echocardiography. ResultsAccording to HOMA-IR levels, patients were categorized as having IR (HOMA-IR score ≥2.5; n = 53) or not having IR (HOMA-IR score <2.5; n = 133). Insulin resistance was determined in 28.4% of study patients. Compared with the non-IR group, the IR group had been receiving HD longer; had greater body mass index; and had higher serum creatinine, uric acid, triglyceride, insulin, and C-reactive protein concentrations, leukocyte count, and LVMI (P < 0.05). Patients with increased LVMI had significantly higher body mass index, systolic blood pressure, serum cholesterol and C-reactive protein concentrations, and HOMA score. At multivariate analysis, systolic blood pressure (β = 0.22; P = 0.03) and HOMA score (β = 0.26; P = 0.01) affected LVMI. ConclusionsInsulin resistance and hypertension are independent risk factors for left ventricular hypertrophy in non-diabetic patients with uremia who are receiving HD. Further studies are needed to indicate the benefits of improving IR for cardiovascular mortality in this subgroup of patients with uremia.

Measurement of free GH and bioactive IGF-I in non-diabetic haemodialysis patients treated with GH for 7 days

End-stage renal failure (ESRF) patients demonstrate augmented growth hormone (GH) secretion, but normal insulin-like growth factor-I (IGF-I) concentrations, indicating a state of GH resistance. To test this hypothesis, we compared the IGF-I response with exogenous GH in haemodialysis patients and healthy controls, with special focus on free GH and bioactive IGF-I. Ultrafiltered free GH and total GH were measured in serum collected hourly for 24 h at baseline and after 7 days of recombinant human (rh) GH (50 µg/kg/day) treatment in 11 non-diabetic haemodialysis patients and 10 matched controls. Serum levels of bioactive IGF-I (determined by cell-based IGF-I receptor activation assay), total IGF-I and the GH-binding protein (GHBP) were assayed twice daily. At baseline, patients showed elevated total GH (24 ± 5 versus 9 ± 1 µg/L × h, P < 0.02), free GH (21 ± 5 versus 7 ± 1 µg/L × h, P < 0.02), reduced GHBP (1.5 ± 0.3 versus 2.5 ± 0.2 nmol/L, P < 0.01), high-normal total IGF-I (173 ± 18 versus 135 ± 14 µg/L, P = 0.12) and subnormal bioactive IGF-I (2.1 ± 0.3 versus 2.8 ± 0.2 µg/L, P < 0.05) when compared with controls. After 7 days of rhGH treatment, there was a greater GH increase in the non-diabetic haemodialysis patients than in controls (total GH: 293 ± 33 versus 166 ± 13 µg/L × h, P < 0.001; free GH: 284 ± 40 versus 126 ± 15 µg/L × h, P < 0.001). GHB remained unaffected and total IGF-I increased to the same extent in patients and controls (701 ± 87 versus 572 ± 33 µg/L, P = 0.17), whereas bioactive IGF-I tended to be lower in patients (5.37 ± 0.55 versus 6.63 ± 0.25 µg/L, P < 0.10). When adjusting for the actual increments in plasma GH, the ability of exogenous GH to stimulate bioactive IGF-I levels was reduced by ~50% in ESRF (P < 0.02), whereas the response of total IGF-I remained normal (74%; P= 0.18) The study demonstrates that ESRF is associated with markedly elevated serum levels of free GH. Furthermore changes in bioactive, but not immunoreactive, IGF-I indicated that the hepatic sensitivity to GH was reduced by 50% in ESRF patients. Clearly, the physiological importance of our observations awaits further studies, but they suggest that changes in total IGF-I may not necessarily reflect changes in the endogenous activity of IGF-I in ESRF patients on GH treatment.

Plasma Protein Characteristics of Long-Term Hemodialysis Survivors

Hemodialysis (HD) patients are under recurrent circulatory stress, and hemodialysis has a high mortality rate. The characteristics of plasma proteomes in patients surviving long-term HD remain obscure, as well as the potential biomarkers in predicting prognoses. This study reports the proteome analyses of patient plasma from non-diabetic long-term HD (LHD, dialysis vintage 14.9±4.1 years, n = 6) and the age/sex/uremic etiology-comparable short-term HD (SHD, dialysis vintage 5.3±2.9 years, n = 6) using 2-DE and mass spectrometry. In addition, a 4-year longitudinal follow-up of 60 non-diabetic HD patients was subsequently conducted to analyze the baseline plasma proteins by ELISA in predicting prognosis. Compared to the SHD, the LHD survivors had increased plasma vitamin D binding proteins (DBP) and decreased clusterin, apolipoprotein A-IV, haptoglobin, hemopexin, complement factors B and H, and altered isoforms of α1-antitrypsin and fibrinogen gamma. During the 45.7±15 months for follow-up of the 60 HD patient cases, 16 patients died. Kaplan-Meier analysis demonstrated that HD patients with the lowest tertile of the baseline plasma DBP level have a significantly higher mortality rate. Multivariate Cox regression analysis further indicated that DBP is an independent predictor of mortality. In summary, the altered plasma proteins in LHD implicated accelerated atherosclerosis, defective antioxidative activity, increased inflammation/infection, and organ dysfunction. Furthermore, lower baseline plasma DBP in HD patients is related to mortality. The results suggest that the proteomic approach could help discover the potential biomarker in HD prognoses.

Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis

Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors. Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay. Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD. Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.

Sex hormones and free androgen index in non-diabetic male hemodialysis and renal transplanted patients

Ageing and diabetes mellitus (DM) are known to affect sex hormones. Several studies have reported on sex hormones in male hemodialysis patients (HDPs) and renal transplant recipients (RTRs). None of those studies had excluded the effect of either ageing or DM, which might be one of the reasons why those studies had contradicting results. The aim of this study was to calculate free androgen index (FAI), assess the level of sex hormones in non-diabetic male (NDM) HDPs and RTRs whose ages were below 50 years, and to compare our findings with those of the others. In this study, NDM HDPs and RTRs had equal total testosterone (TT) level that was not significantly different from that of the controls; however, their FAI was significantly lower than that of the controls. Levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol, prolactin, and sex hormone binding globulin (SHBG) were higher in those two patients groups than in the control group. In conclusion, NDM HDPs and RTRs had TT level that was not different from that of the controls, but they had abnormally low FAI level and abnormally elevated levels of LH, FSH, estradiol, prolactin, and SHBG. Key words: Free androgen index, sex hormones, hemodialysis, transplantation.

Association between vascular access failure and microparticles in hemodialysis patients

BackgroundVascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses.MethodsWe investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42− or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration.ResultsThe levels of EMP (both CD31+CD42− and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42−EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42−EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival ≥ 4 years).ConclusionElevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients.

Interleukin-6 -634 C/G and -174 G/C Polymorphisms in Korean Patients Undergoing Hemodialysis

Background/AimsChronic inflammatory status is a possible risk factor for vascular access dysfunction in hemodialysis (HD) patients, but susceptibility differences appear among individuals. Interleukin (IL)-6 is a well-known inflammatory cytokine with various polymorphisms. We examined whether IL-6 polymorphisms are associated with vascular access dysfunction in HD patients.MethodsA total of 80 HD patients (including 42 diabetic patients) were enrolled. Polymorphisms in the IL-6 gene promoter (-634 C/G and -174 G/C) were studied using restriction length polymorphism polymerase chain reaction analysis. Vascular access patency was compared between the patient groups with respect to IL-6 polymorphisms. An additional 89 healthy individuals were enrolled in the control group. Plasma IL-6 levels were de termined by enzyme-linked immunosorbent assay.ResultsThe GG genotype and G allele at position -634 in the IL-6 promoter were more frequently observed in HD patients than in controls. Furthermore, the distribution of the -634 polymorphism differed according to vascular access patency in non-diabetic HD patients. However, the G allele was not a significant risk factor for early access failure. No significant association appeared between the IL-6 -634 C/G polymorphism and plasma IL-6 levels. The C allele of the IL-6 -174 G/C polymorphism was not detected in our study population.ConclusionsThe IL-6 -634 G allele appears with greater frequently in patients with end-stage renal disease and may be associated with vascular access dysfunction in non-diabetic HD patients.

Association of adiponectin with cardiovascular events in diabetic and non-diabetic hemodialysis patients

Adiponectin is a novel collagen-like protein synthesized by white adipose tissue. Its levels are decreased in obesity, type-2 diabetes and insulin-resistant states, and are increased in chronic renal failure. It has anti-inflammatory and anti-atherogenic properties. This study was planned to evaluate the levels of adiponectin in uremic patients with and without diabetes and to find any relationship between adiponectin levels and some cardiovascular risk factors, and to determine the possible predictive value of adiponectin for cardiovascular complications (CVC). The study included 100 subjects, 20 of them were healthy subjects and served as the control group (group I), 40 were uremic non-diabetic patients (group II) (half of them were without CVC, group IIA, and the other half were patients with CVC, group IIB) and, lastly, 40 uremic diabetic patients (group III) (half of them were without CVC, group IIIA, and the other half were patients with CVC, group IIIB). All subjects were subjected to complete clinical examination, including determination of mean arterial blood pressure (MABP), body mass index (BMI), waist to hip ratio, routine laboratory investigations, fasting plasma glucose, fasting plasma insulin, lipid profile (cholesterol, TG, LDL, HDL), determination of insulin resistance by homeostasis model assessment index (HOMA-IR) and estimation of serum levels of adiponectin. There was a significant increase in serum adiponectin levels in all the uremic patients (group II and group III) when compared with the control (group I) group, P <0.01; also, serum adiponectin levels were significantly decreased in uremic diabetic patients (group III) when compared with uremic non-diabetic patients (group II), P <0.01; but this was still higher than in the controls. The patients with CVC, whether uremic non-diabetic (group IIB) or uremic diabetic (group IIIB), had a significant decrease in serum adiponectin levels when compared with patients without CVC (group IIA and group IIIA), P <0.01. Serum adiponectin has a significant positive correlation with HDL and a significant negative correlation with MABP, BMI, plasma insulin, HOMA-IR, LDL, TG and cholesterol in all the patients. Therefore, it can be concluded that adiponectin levels in uremic patients, whether diabetic or non-diabetic, may be a good indicator of cardiovascular disease risk.

Oxidative Stress and Raloxifene

Dear Editor, We read “Effects of raloxifene on bone metabolism in hemodialysis patients with type 2 diabetes” by Saito et al. (1) with a great interest. This paper shows that raloxifene works in diabetic or non-diabetic hemodialysis patients to reduce bone loss. This was shown by means of significant decrease in NTx and a significant increase in SOS measurements in both treatment groups compared to the un-treated control arms. We would like to draw attention to the possible anti-oxidant role of raloxifene regarding beneficial effects on the bone turnover markers as well as bone mass. The targeted population in this study consisted hemodialysis patients with type 2 diabetes who under a great oxidative stress related to both renal failure and diabetes (2, 3). We have previously demonstrated that women with post-menopausal osteoporosis had lower erythrocyte catalase (CAT) enzyme activity and higher erythrocyte malondialdehyde (MDA) levels (4). Interestingly, in another study we showed that raloxifene treatment for 3 months significantly enhanced CAT enzyme activity and reduced the MDA levels in women with PMO (5). Similar anti-oxidant effects of raloxifene were confirmed by others (6). Although neither discussed nor studied by means of enzymatic parameters, we would like to attract Authors’ attention to the potent anti-oxidant effect of raloxifene particularly in this special study population. Significant decrease in N-terminal cross-linking telopeptide of type I collagen (NTx) as well as oxidative stress parameters has been achieved with the use of potent anti-oxidants (lycopene) in patients with PMO (7). We think the results of this present study should also be admissible regarding the anti-oxidant effects of raloxifene particularly in hemodialysis patients with type 2 diabetes who are under great oxidative stress.

Erratum to: Endogenous soluble receptor of advanced glycation end-products (esRAGE) is negatively associated with vascular calcification in non-diabetic hemodialysis patients

Erratum to: Endogenous soluble receptor of advanced glycation end-products (esRAGE) is negatively associated with vascular calcification in non-diabetic hemodialysis patients

Anti-PF4/heparin antibodies are associated with arteriovenous fistula thrombosis in non-diabetic hemodialysis patients

Anti-platelet factor 4/heparin complex antibodies (anti-PF4/heparin Ab) have been found to cause heparin-induced thrombocytopenia (HIT), a clinical syndrome thrombocytopenia and thrombosis. There is still controversy as to whether the presence of anti-PF4/heparin antibodies in hemodialysis patients augments clot formation in access fistula thrombosis, peripheral artery disease (PAD), and coronary heart disease (CHD). We enrolled 111 non-diabetic hemodialysis patients without liver cirrhosis and without an ankle-brachial index (ABI) ≥1.3 (arterial calcification). ABI measurements were performed and patients with an ABI≤0.9 were defined as having PAD and included in the PAD group. ELISA was used for determination of anti-PF4/heparin Ab. Correlation factors include PAD, native arteriovenous fistula (AVF) thrombosis, platelet count, and CHD. Thirty-seven of 111 patients (33.3%) presented with anti-PF4/heparin Ab. Thirty-eight of 111 patients (34%) had PAD; fourteen of these patients (36.8%) and 23/73 of patients without PAD (31.5%) were anti-PF4/heparin Ab-positive (P=0.57). Fifty-two of 111 patients (46.8%) had AVF thrombosis; twenty-three of these patients (44.2%) and 14/59 of patients without AVF thrombosis (23.7%) were anti-PF4/heparin Ab-positive (P=0.02). The odds ratio for AVF thrombosis was 2.55 (95% CI 1.14-5.71) for anti-PF4/heparin Ab-positive patients. Thirty-two of 111 patients (28.8%) had thrombocytopenia (platelet count <140×10(3)/μL); eleven of these patients (34.3%) and 26/79 patients without thrombocytopenia (32.9%) were anti-PF4/heparin Ab-positive (P=0.88). Ten of 111 patients (9%) had CHD; two of these patients (20%) and 35/101 patients without CHD (34.6%) were anti-PF4/heparin Ab-positive (P=0.49). We found that anti-PF4/heparin Ab may contribute to an increased risk of AVF thrombosis in non-diabetic hemodialysis patients.