Ender Hur

Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study

BACKGROUND Online haemodiafiltration (OL-HDF) is considered to confer clinical benefits over haemodialysis (HD) in terms of solute removal in patients undergoing maintenance HD. The aim of this study was to compare postdilution OL-HDF and high-flux HD in terms of morbidity and mortality. METHODS In this prospective, randomized, controlled trial, we enrolled 782 patients undergoing thrice-weekly HD and randomly assigned them in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. The mean age of patients was 56.5 ± 13.9 years, time on HD 57.9 ± 44.6 months with a diabetes incidence of 34.7%. The follow-up period was 2 years, with the mean follow-up of 22.7 ± 10.9 months. The primary outcome was a composite of death from any cause and nonfatal cardiovascular events. The major secondary outcomes were cardiovascular and overall mortality, intradialytic complications, hospitalization rate, changes in several laboratory parameters and medications used. RESULTS The filtration volume in OL-HDF was 17.2 ± 1.3 L. Primary outcome was not different between the groups (event-free survival of 77.6% in OL-HDF versus 74.8% in the high-flux group, P = 0.28), as well as cardiovascular and overall survival, hospitalization rate and number of hypotensive episodes. In a post hoc analysis, the subgroup of OL-HDF patients treated with a median substitution volume >17.4 L per session (high-efficiency OL-HDF, n = 195) had better cardiovascular (P = 0.002) and overall survival (P = 0.03) compared with the high-flux HD group. In adjusted Cox-regression analysis, treatment with high-efficiency OL-HDF was associated with a 46% risk reduction for overall mortality {RR = 0.54 [95% confidence interval (95% CI) 0.31-0.93], P = 0.02} and a 71% risk reduction for cardiovascular mortality [RR = 0.29 (95% CI 0.12-0.65), P = 0.003] compared with high-flux HD. CONCLUSIONS The composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups. In a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival.

Effect of Fluid Management Guided by Bioimpedance Spectroscopy on Cardiovascular Parameters in Hemodialysis Patients: A Randomized Controlled Trial

BACKGROUND Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN Prospective, randomized, and controlled study. SETTING & PARTICIPANTS 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS Ambulatory blood pressure data were not available for all patients. CONCLUSIONS Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Endogenous Testosterone and Mortality in Male Hemodialysis Patients: Is It the Result of Aging?

BACKGROUND AND OBJECTIVES Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile. RESULTS Mean testosterone level was 8.69 ± 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P = 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P = 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses. CONCLUSIONS Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

Introduction. Acute kidney injury (AKI) pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im) daily; Genta group, gentamicin 100 mg/kg/day (im); Genta + vitamin D, gentamicin 100 mg/kg/day (im) in addition to 1α, 25 (OH)2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

The effect of immunosuppressive treatment on arterial stiffness and matrix Gla protein levels in renal transplant recipients

INTRODUCTION Arterial stiffness is a risk marker for cardiovascular events. In this study we aimed to compare the effect on calcineurin inhibitors (CNI) and mammalian Target of Rapamycine inhibitors (mTORi) on arterial stiffness in renal transplant patients. PATIENTS AND METHODS 81 renal transplant patients under CNI-based or mTORi-based protocol for at least 6 months were included in the study. Arterial stiffness was measured by using the SphygmoCor device (AtCor Medical, Sydney, Australia). Vitamin K-dependent, calcification inhibitor matrix Gla protein (MGP) concentrations were quantified by ELISA methods (Biomedica, Vienna, Austria). RESULTS 34 patients were on mTORi-based and 47 on CNI-based immunosuppression. Mean age was 37.9 ± 10.8 (18 - 71) years and 45% were female. Age, gender, graft functions and follow-up period of the groups were similar. Augmentation index was 15.2 ± 12.6% in CNI and 18.8 ± 14.0% in mTORi groups (p > 0.05). There was no difference regarding carotid-femoral pulse wave velocity between groups. Arterial stiffness was positively correlated with age, total cholesterol, LDL cholesterol, mean arterial pressure (MAP) and proteinuria. MGP levels were higher in the mTORi group but were not predictors for carotid-femoral pulse wave velocity. CONCLUSION Rather than specific immunosuppressive drug effects, conventional risk factors, blood pressure and proteinuria are the most important predictors for arterial stiffness in renal transplant patients.

The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats.

INTRODUCTION Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats. METHODS 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 ml isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated. RESULTS Although the MMF and resting groups showed beneficial effects on ultrafiltration and D1/D0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGFβ1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm2 of submesothelial area, decreased in the treatment group. CONCLUSIONS MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.

Hypervolemia for Hypertension Pathophysiology: A Population-Based Study

Objectives. Hypertension and hypervolemia relationship was proven among renal disease, although it is not known in normal population. Present study determines the fluid distribution defects in relation to blood pressure. Material and Methods. In a population-based survey in Turkey demographics, height, weight, blood pressure, urine analysis, and serum creatinine measurements were recorded. Bioimpedance measured with the Body Composition Monitor. Results. Total 2034 population of 71.6% male, mean age 47 ± 12.6 (18–89) years, systolic blood pressure (SBP) 134.7 ± 20, diastolic blood pressure 77.9 ± 11.6 mmHg. Body mass index (BMI) was 28.5 ± 4.5 (15.8–50.6) kg/m2; overhydration was 0.05 ± 1.05 L. There was a correlation between extracellular water (ECW)/height and SBP (r = 0.21, P < 0.001). Receiver operating characteristic (ROC) curve with the performance of 0.60 (P < 0.001) that showed cut-off value of ECW/height was 10.06 L/m, with the 69% sensitivity and 45% specificity for SBP: 140 mmHg values. Risk factors for high SBP were increase of ECW/Height, age, BMI and presence of diabetes. ECW/height, SBP, and fat tissue index (FTI) increased in BMI categories (low, normal, and obese) and in diabetics. SBP and FTI were lower in smokers. Conclusions. High blood pressure may be accompanied by increased extracellular volume indices. In the future volume status assessment could be of use in evaluating the effectiveness of pharmacological intervention in the treatment of hypertension.

Octreotide lessens peritoneal injury in experimental encapsulated peritoneal sclerosis model

Aim:  Encapsulated peritoneal sclerosis is characterized by neoangiogenesis and fibrosis. Octreotide, a somatostatin analogue is a well‐known antifibrotic, antiproliferative and anti‐angiogenic agent. The aim of the study is to evaluate the effects of octreotide in encapsulated peritoneal sclerosis‐induced neoangiogenesis and fibrosis and compare the results with resting.

Progression of graft fibrosis under mammalian target of rapamycin inhibitor-based regimen

Aim:  Nephrotoxic potential of mammalian target of rapamycin inhibitors (mTORi) is different from calcineurin inhibitors (CNI). The aim of this study is to investigate the interstitial fibrosis (ci) and tubular atrophy (ct) progression from the baseline to first year under a mTORi‐based, CNI‐free regimen.

The Mean Platelet Volume and Atherogenic Index of Plasma in Nondipper Normotensive Individuals Compared to Dippers

Mean platelet volume (MPV) is a determinant of platelet activation. Atherogenic index of plasma (AIP), which is defined as the logarithm of the ratio of plasma level of triglycerides to the level of high-density lipoprotein (HDL)-cholesterol (log[ TG/HDL-C]), has recently been used as a marker of atherogenicity. This study included 104 normotensive individuals. Mean platelet volume and AIP were measured in all patients. Nondipper individuals (8.6 ± 0.9 fL, 0.3 ± 0.2) demonstrated higher values of MPV and AIP compared with dippers (7.9 ± 1.1 fL, 0.1 ± 0.2) (P < .001 and < .001, respectively). Mean platelet volume and AIP have a positive correlation with insufficient decline in nocturnal blood pressure.