Lowering dialysate sodium improves systemic oxidative stress in maintenance hemodialysis patients.

PURPOSE: The purpose of the current prospective study was to evaluate the effects of low sodium dialysate on oxidative stress parameters, blood pressure (BP) and endothelial dysfunction in maintenance hemodialysis (HD) patients. METHODS: After baseline measurements were taken, the dialysate sodium concentration was reduced from 140 to 137 mEq/L. Oxidative stress parameters and flow-mediated dilatation (FMD %) were measured before and after 6 months of HD with low sodium dialysate. Interdialytic weight gain (IDWG) and pre- and post-dialysis BP were monitored during the study. RESULTS: A total of 52 patients were enrolled and 41 patients completed the study. There was a significant reduction in systolic blood pressure at the end of the study [130.00 (90.00-190.00) vs. 120.00 (90.00-150.00), p < 0.001]. Similarly, there were significant improvements in IDWG [2670.00 (1670.00-4300.00) vs. 1986.00 (1099.00-3998.00), p < 0.001] and FMD % [7.26 (4.55-8.56) vs. 9.56 (6.55-12.05), p < 0.001]. Serum MDA levels (p < 0.001) were significantly decreased; serum SOD (p < 0.001) and GPx (p < 0.001) activities were significantly increased after low sodium HD compared to standard sodium HD. CONCLUSION: Our data seem to suggest a potential role of 137 mEq/L sodium dialysate for improving hemodynamic status, endothelial function and reducing oxidative stress than 140 mEq/L sodium dialysate in maintenance HD patients.

Epicardial fat tissue thickness is correlated with diminished levels of co-enzyme Q10, a major antioxidant molecule among hemodialysis patients.

OBJECTIVES: Accelerated atherosclerosis is the major cause of mortality in patients on chronic maintenance hemodialysis (HD). Epicardial fat tissue (EFT) is a new risk factor in cardiovascular disease (CVD). The aim of this study was to evaluate the relation between plasma coenzyme Q10 levels (Co-Q10) which is a potent physiologic antioxidant and EFT thickness in HD patients. DESIGN AND METHODS: Seventy one chronic HD patients and 65 age and sex matched healthy individuals were included in the study. Plasma Co-Q10 levels were performed by high-performance liquid chromatography (HPLC) measurements. EFT was measured by transthoracic echocardiograpy (TTE) performed with a VIVID 7 instrument. RESULTS: Plasma Co-Q10 levels (1.36±0.43 vs 2.53±0.55, p<0.001) were significantly lower in HD patients compared to controls. EFT was significantly increased in HD patients compared to healthy controls (6.53±1.01 vs. 5.79±1.06 mm respectively, p<0.001). Correlation analysis showed that plasma Co-Q10 levels were inversely correlated with EFT (r=-0.263, p<0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. According to linear regression analysis, age, BMI, total cholesterol and Co-Q10 levels were found to be independent predictors of EFT (adjusted r(2)=0.38, p<0.001). CONCLUSION: This study demonstrated that EFT thickness was significantly higher among HD patients compared to healthy controls. In addition; this study was the first to demonstrate an inverse correlation between EFT thickness and Co-Q10 levels in this patient population.

Epicardial fat thickness is associated with impaired coronary flow reserve in hemodialysis patients.

Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD) patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of this study was to evaluate the association between EFT and coronary artery flow reserve (CFR), which is an early indicator of endothelial dysfunction in coronary vessels of HD patients. We performed a cross-sectional study including 71 chronic HD patients and 65 age- and sex-matched healthy controls. Epicardial fat tissue was significantly higher in HD patients when compared to healthy controls (6.53 ± 1.01 mm vs. 5.79 ± 1.06 mm, respectively, P < 0.001). On transthoracic Doppler echocardiography, CFR values were significantly lower in HD patients when compared to healthy controls (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001). Correlation analysis showed CFR values to be inversely correlated with EFT (r = -0.287, P < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. Artery flow reserve, age, body mass index and total cholesterol levels were independently correlated with EFT thickness. This study demonstrated that EFT was significantly higher among HD patients compared to healthy controls. In addition, this study was the first to demonstrate an inverse correlation between EFT and CFR in this patient population.

Decreased serum selenium levels are correlated with diminished coronary flow reserve among hemodialysis patients.

Cardiovascular diseases are the main reason of high mortality among hemodialysis patients. Decreased serum selenium levels may have a role in accelerated atherosclerosis in this patient group. The hypothesis of this study was to show a correlation between decreased serum selenium levels and coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in HD patients. Seventy-one chronic hemodialysis patients and age 65 and sex-matched healthy controls were included in the study. Plasma selenium levels were measured by spectrophotometry, and coronary flow reserve was assessed by transthoracic Doppler echocardiography. Serum selenium levels (34.16 ± 6.15 ng/ml vs. 52.4 ± 5.51 ng/ml, P < 0.001) and coronary flow reserve values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in hemodialysis patients compared with controls, respectively. There was a significant positive correlation between coronary flow reserve and serum levels of selenium (r = 0.676, P < 0.001). A linear regression analysis showed that serum levels of selenium were independently and positively correlated with coronary flow reserve (regression coefficient = 0.650, P < 0.05). This study was the first to show a positive and independent correlation between decreased selenium levels and diminished coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in hemodialysis patients. Our data suggest that decreased serum selenium levels may facilitate the development of endothelial dysfunction and disruption of coronary flow reserve which occur before the development of overt atherosclerosis.

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients.

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy-one chronic HD patients and 65 age- and sex-matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high-performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.

Effect of the direct renin inhibitor aliskiren in the prevention of experimental contrast-induced nephropathy in the rat.

BACKGROUND: Renal vasoconstriction, activated by the renin-angiotensin system, plays a pivotal role in the pathogenesis of contrast-induced nephropathy (CIN). The purpose of this study was to evaluate the effect of aliskiren, a direct renin inhibitor, for the prophylaxis of experimental CIN in the rat. METHODS: Thirty-two Wistar albino rats were divided into four groups of 8 rats each, namely the control (C), aliskiren (A), contrast media (CM) and aliskiren plus contrast media (ACM) groups. Aliskiren was given orally at a dose of 50 mg/kg/day once daily for 5 consecutive days. CIN was induced by intravenous administration of indomethacin, N-nitro-L-arginine methyl ester and high-osmolar contrast medium meglumine amidotrizoate. Renal function parameters, kidney histology and tubular expression of vascular endothelial growth factor were determined. RESULTS: Mean serum creatinine was significantly lower (p < 0.001) and mean creatinine clearance was higher (p < 0.001) in the ACM group compared with the CM group. However, there were no differences between the ACM and CM groups in terms of tubular necrosis, proteinaceous casts, medullary congestion and vascular endothelial growth factor expression. CONCLUSION: Our preliminary data seem to suggest a potential role of aliskiren for the prophylaxis of CIN in an experimental rat model.

Effects of rapamycin and tacrolimus on mature endothelial cells and endothelial progenitor cells.

OBJECTIVE: To investigate the effects of the potent immunosuppressive agents tacrolimus and rapamycin on the number of circulating mature endothelial cells and circulating endothelial progenitor cells in an experimental model. METHODS: It was an experimental study performed from December 2007 to January 2008 in which the effects of the immunosuppressive agents tacrolimus and rapamycin on endothelial progenitr cells and circulating mature endothelial cells were analysed on 24 male wistar albino rats in a controlled environment model. Circulating cell populations were measured by flow-cytometric analysis. Maun-Whitney U test and analysis of vartiance were used for statistical purposes. RESULTS: Rapamycin increased the number of circulating mature endothelial cells approximately 2-fold compared to tacrolimus. The number of endothelial progenitor cells also was increased in the peripheral blood of rats treated with rapamycin compared to those treated with tacrolimus. CONCLUSION: The study showed that treatment with rapamycin is associated with an increase in endothelial progenitor cells and circulating mature endothelial cells. This increase may be associated with endothelial cell damage and repair.

Protective effect of the vasopressin agonist terlipressin in a rat model of contrast-induced nephropathy.

BACKGROUND/AIMS: Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute renal failure. Terlipressin, a long-acting analog of vasopressin, may improve renal function. This study aimed to investigate the possible protective effect of terlipressin against the development of experimental CIN in rats. METHODS: Wistar albino rats (n = 32) were allocated randomly into four equal groups of 8 each, i.e. control, terlipressin, contrast media (CM), and terlipressin plus contrast media (TCM). CIN was induced by intravenous administration of indomethacin (10 mg/kg), N-nitro L-arginine methyl ester (L-NAME, 10 mg/kg, twice at 15 and 30 min), and high-osmolar contrast media meglumine amidotrizoate 60%. Renal function parameters, kidney histology, and tubular expression of vascular endothelial growth factor (VEGF) were determined. RESULTS: Mean serum creatinine levels were decreased (p < 0.05) and creatinine clearance (p < 0.05) increased in the TCM group compared with the CM group. Notably, rats in the TCM group displayed less tubular necrosis (p < 0.05), medullary congestion (p < 0.05), and a reduced tubular expression of VEGF (p < 0.05) compared with the CM group. CONCLUSION: These results demonstrate that terlipressin can inhibit the development of CIN.

A comparison of different methods for the determination of glomerular filtration rate in elderly patients with chronic renal failure.

OBJECTIVE: The aim of the present study was to asses the accuracy of prediction equations in elderly patients with advanced renal disease (ARD). PATIENTS AND METHODS: Twenty-three elderly patients (>60 years) with chronic kidney disease (CKD) stages 3-5 underwent technetium-99 m-diethylenetriaminepentaacetic acid (Tc-99m-DTPA) radionuclide measurement of glomerular filtration rate (GFR). To predict GFR, estimation formulas [Cockcroft-Gault (CG), 6-variable Modification of Diet in Renal Disease (6-var-MDRD) and the corrected 24-hour creatinine clearance (24-h CCL) method] were used. Estimates of bias and precision were obtained to compare prediction equations of GFR with standard radionuclide measurement. RESULTS: In the present study, all the prediction equations overestimated the GFR measured with the radionuclide method. Six-var-MDRD and 24-h CCL methods correlated better with standard radionuclide measurements compared to the CG formula (Rc of 0.53 and 0.50 vs. 0.41, respectively) as for GFR prediction, but they were still insufficiently accurate. CONCLUSION: Glomerular filtration rate prediction equations correlate poorly with standard radionuclide measurements and their use may lead to late initialization of renal replacement therapy in elderly patients with ARD. Therefore, measurement by standard radionuclide method (Tc-99m-DTPA) is recommended to accurately assess GFR in elderly patients with ARD.