Do Statins Counteract the Effect of Antidiabetic Drugs? Results of the SCEAD Study.

PURPOSE: Diabetes and dyslipidemia are leading causes of mortality and morbidity. According to international guidelines, statins are the cornerstone of treatment in patients with diabetes and/or dyslipidemia. However, statins and antidiabetic agents have opposite pharmacological effects, because statins, particularly atorvastatin and rosuvastatin, impair glucose homeostasis, increasing the risk of new-onset diabetes, whereas antidiabetic drugs improve glycemic homeostasis. The aim of this study was to investigate the effect of atorvastatin, rosuvastatin, and pitavastatin on glucose homeostasis in patients with type 2 diabetes mellitus (T2DM) and dyslipidemia during stable treatment with hypoglycemic drugs. MATERIALS AND METHODS: The study was conducted as a pilot, prospective, randomized, open label, parallel group with blinded-endpoints (PROBE) study. Of 180 recruited patients with T2DM and dyslipidemia, 131 were randomized to atorvastatin (n=44), rosuvastatin (n=45), and pitavastatin (n=42) and treated for 6 months. RESULTS: Fasting plasma glucose (FPG) marginally decreased in patients assigned to atorvastatin (-3.5 mg/dL, p=0.42) and rosuvastatin (-6.5 mg/dL, p=0.17), while it decreased much more in patients treated with pitavastatin (-19.0 mg/dL, p<0.001). Mean glycated hemoglobin A1c (HbA1c ) values remained unchanged during treatment with atorvastatin (-0.10%, p=0.53) and rosuvastatin (0.20%, p=0.40), but were significantly reduced with pitavastatin (-0.75%, p=0.01). Atorvastatin, rosuvastatin, and pitavastatin significantly lowered (p<0.001) plasma levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides, while high-density lipoprotein-cholesterol (HDL-C) levels increased significantly (p=0.04) only in the pitavastatin group. CONCLUSION: The results of the present study suggest that pitavastatin affects FPG and HbA1c less than atorvastatin and rosuvastatin in patients with T2DM and concomitant dyslipidemia. Lipid-lowering efficacies were not significantly different among the three statins, with the exception of HDL-C, which increased significantly with pitavastatin. Although the pharmacological mechanism of pitavastatin on glucose homeostasis in patients with T2DM during stable antidiabetic therapy is not known, it can be assumed that pitavastatin has less drug interaction with hypoglycemic agents or that it increases plasma levels of adiponectin.

A prospective study of living kidney donors: 6 years follow-up from a cardiovascular disease risk perspective.

OBJECTIVE: The purpose of this prospective study was to evaluate the clinical, laboratory, and donation-specific outcomes of living kidney donors 6 years after donation. METHODS: We included a total of 93 kidney donors and 54 age- and sex-matched individuals as control group through a type 2 cohort consecutive recruitment. We detected kidney function abnormalities and the presence of hypertension, diabetes, and cardiovascular events during the 6 years follow-up period. RESULTS: The mean serum creatinine levels were higher (p<0.001), and the estimated glomerular filtration rate levels were lower (p<0.001) in living kidney donors 6 years after donation when compared with controls. The protein/creatinine ratio of the study population was also higher (p=0.014). There was no difference in outcomes between the groups for end-stage kidney disease and cardiovascular mortality. A higher rate of new-onset hypertension (6.4 vs. 32.9%), diabetes mellitus (0.0 vs. 4.3%), chronic kidney disease (0.0 vs. 2.1%), and cardiovascular disease (0.0 vs. 2.1%) was demonstrated among donors 6 years after donation (p<0.001, respectively). CONCLUSION: Our data have demonstrated that the reduction in Glomerular filtration rate induced by kidney donation might cause an increase in adverse renal and cardiovascular events.

A prospective study of living kidney donors: 6 years follow-up from a cardiovascular disease risk perspective

SUMMARY OBJECTIVE: The purpose of this prospective study was to evaluate the clinical, laboratory, and donation-specific outcomes of living kidney donors 6 years after donation. METHODS: We included a total of 93 kidney donors and 54 age- and sex-matched individuals as control group through a type 2 cohort consecutive recruitment. We detected kidney function abnormalities and the presence of hypertension, diabetes, and cardiovascular events during the 6 years follow-up period. RESULTS: The mean serum creatinine levels were higher (p<0.001), and the estimated glomerular filtration rate levels were lower (p<0.001) in living kidney donors 6 years after donation when compared with controls. The protein/creatinine ratio of the study population was also higher (p=0.014). There was no difference in outcomes between the groups for end-stage kidney disease and cardiovascular mortality. A higher rate of new-onset hypertension (6.4 vs. 32.9%), diabetes mellitus (0.0 vs. 4.3%), chronic kidney disease (0.0 vs. 2.1%), and cardiovascular disease (0.0 vs. 2.1%) was demonstrated among donors 6 years after donation (p<0.001, respectively). CONCLUSION: Our data have demonstrated that the reduction in Glomerular filtration rate induced by kidney donation might cause an increase in adverse renal and cardiovascular events.

Can Ischemia Modified Albumin (IMA) Levels Be a Predictor of Acute Pancreatitis?

BACKGROUND: We aimed to evaluate the value of ischemia modified albumin (IMA) as a prognostic marker in acute pancreatitis (AP) patients, determine whether it is efficient in assessing the disease severity or not, and to estimate the correlation between IMA and the inflammatory markers, prognostic markers and scoring systems routinely used in clinical practice. METHODS: 100 adult patients (18 years and older) who have been hospitalized and evaluated with AP diagnosis in Tepecik Training and Research Hospital,, Department of Gastroenterology, between April 1, 2017 and April 1, 2018 have been enrolled in the study. Patients have been stratified disease etiology (biliary or non-biliary). The non-biliary group has been divided into subgroups as alcoholic, lipemic, or idiopathic. Disease severity has been categorized as mild, moderate, or severe pancreatitis according to the Atlanta classification. Ranson, Harmless Acute Pancreatitis Score (HAPS), Bedside Severity Index for Acute Pancreatitis (BISAP) scores have been determined for each patient. Patients have been grouped as necrotizing or edematous according to the Atlanta classification. RESULTS: According to our findings, IMA has been found to be correlated with disease severity, Ranson and BISAP scores, and procalcitonin levels. We have observed that some laboratory parameters including blood urea nitrogen and hematocrit levels and HAPS scoring system are not correlated to IMA. CONCLUSION: Our study is the first study to compare multiple prognostic factors with IMA in AP patients. In our study, the association between IMA and AP has been evaluated in the context of prognostic scoring and disease severity.

Hypertension in Kidney Transplant Recipients: Where Are We Today?

PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death and allograft loss among kidney transplant recipients, and hypertension is an independent risk factor for cardiovascular morbidity of this patient population. The etiology of hypertension is multifactorial, including pre-transplant volume overload, post-transplant recipient and donor-associated variables, and transplant-specific causes (immunosuppressive medications, allograft dysfunction and surgical complications such as transplant artery stenosis). RECENT FINDINGS: No randomized controlled trials have assessed the optimal blood pressure targets and explored the best antihypertensive regimen for kidney transplant recipients. According to the large observational studies, it is reasonable to achieve a blood pressure goal of equal to or less than 130/80 mmHg in the long-term follow-up for minimizing the cardiovascular morbidity. The selection of antihypertensive agents should be based on the patient's co-morbidities; however, the initial choice could be calcium channel blockers especially in the first few months of transplantation. In patients with cardiovascular indications of renin-angiotensin-aldosterone system inhibition, given the well-described benefits in diabetic and proteinuric patients, it is reasonable to consider the use of renin-angiotensin-aldosterone system inhibitors. There is a need for future prospective trials in the transplant population to define optimal blood pressure goals and therapies.

Once- vs Twice-Daily Tacrolimus: Survival Rates and Side Effects: Single-Center Experience.

BACKGROUND: This study aimed to determine whether de novo, prolonged-release tacrolimus- (PR-tacro) based immunosuppressive regimen affected graft and patient survival when compared to an immediate-release, twice-daily, tacrolimus- (IR-tacro) based regimen in kidney transplant recipients. We also aimed to determine the difference between the frequency of side effects, including diabetes control, in study groups. METHODS: A total of 115 standard risk kidney transplant recipients were enrolled in this single center, retrospective study. Fifty-two patients received PR-tacro and 63 patients received IR-tacro as a calcineurin inhibitor. The primary outcome measures included incidence of graft loss and delayed graft function (DGF), biopsy-proven acute rejection , graft and patient survival, and creatinine clearance. Secondary outcome measures included the incidence of non-adherence, drug-induced tremor; post-transplant diabetes mellitus diagnosis rate; and control of diabetes in pre-transplant diabetic patients. RESULTS: Baseline characteristics and mean tacrolimus trough levels were comparable between groups. Incidence of graft loss, DGF, and graft and patient survival were similar between groups (P > .05). Mean creatinine clearance level was also similar (P > .05). Mean serum levels of fasting glucose (P < .05) and A1C (P < .05) were lower in PR-tacro group when compared to IR-tacro group. Post-transplant diabetes mellitus diagnosis rate was also lower in PR-tacro group when compared to IR-tacro group (P = .040). CONCLUSION: This study suggests that there is no statistically significant difference between PR-tacro and IR-tacro in terms of patient and graft survival, DGF, and biopsy-proven acute rejection rates in kidney transplant recipients. Post-transplant diabetes mellitus frequency is lower in non-diabetic patients, and glucose metabolism control is better in diabetic patients.

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus.

BACKGROUND: In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. OBJECTIVES: The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. MATERIALS AND METHODS: A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. RESULTS: No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. CONCLUSIONS: These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges.

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.

EDTA interference in electrochemiluminescence ACTH assay.

Background As plasma is the recommended sample type for Roche adrenocorticotropic hormone (ACTH) assay, we evaluated the effect of EDTA concentration on Cobas ACTH assay. Methods Samples containing twofold and fourfold higher concentrations of EDTA were prepared by adding plasma to empty K2EDTA tubes and by making under-filled EDTA tubes. All measurements were performed with four replicates. Results Increased EDTA concentration resulted in a significant decrease in ACTH concentration. Fifty-per cent-filled EDTA tube showed 19% decrease in ACTH concentration and 25% filled EDTA tube showed 50% decrease in ACTH concentration. Conclusion We recommend that inadequately filled EDTA specimens should be rejected when using Cobas ACTH assay.

Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model.

BACKGROUND: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. METHODS: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. RESULTS: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. CONCLUSION: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model.

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n = 32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A + P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4 µg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A + P had lower mean fractional sodium excretion (p < 0.001) as well as higher creatinine clearance (p = 0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p = 0.035) and serum 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p < 0.001) were significantly lower; superoxide dismutase (p = 0.024) and glutathione peroxidase (p = 0.007) activities of renal tissue were significantly higher in group A + P than in group A. The mean scores of tubular necrosis (p = 0.024), proteinaceous casts (p = 0.038), medullary congestion (p = 0.035), and VEGF immunoexpression (p = 0.018) were also lower in group A + P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.

Prevention of peritonitis in newly-placed peritoneal dialysis catheters: efficacy of oral prophylaxis with cefuroxime axetil - a preliminary study.

BACKGROUND: Peritonitis is one of the causes of early peritoneal dialysis (PD) failure in newly-placed catheters. Antibiotic prophylaxis has been recommended to decrease the risk of infection after PD catheter placement. In this study, we compared the efficacy of parenteral versus oral prophylactic cefuroxime axetil for preventing peritonitis after placed PD catheters. METHODS: In total, 67 patients (F/M: 32/35; mean age: 46.6±13.2 years) undergoing 70 percutaneous PD catheter placement procedures were included (in three patients, placement was repeated). In 37 patients (parenteral group), we administered a single intravenous (IV) 750-mg dose of cefuroxime axetil, approximately 30 min before placement. In the oral group, 33 patients received a 500-mg dose of oral cefuroxime axetil 1 hour before the procedure and the patients continued that twice daily for 3 days. Patients were evaluated for peritonitis over the following 14 days. The costs of both oral and parenteral forms of cefuroxime axetil were calculated. RESULTS: The two groups were similar regarding age and gender. Three patients (9%) in the oral group and three (8.1%) in the parenteral group developed peritonitis (P=0.578). All were responded to therapy for peritonitis. The cost of parenteral prophylaxis was $US 7.58, while that of the oral form was $US 3.92. CONCLUSION: For patients undergoing percutaneous PD catheter insertion, a 3-day regimen of oral cefuroxime axetil for preventing early peritonitis was safe, equally effective, and had lower cost comparing with single intravenous dose of the same agent.

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.

Cinacalcet may improve oxidative DNA damage in maintenance hemodialysis patients: an observational study.

BACKGROUND: Oxidative stress is accepted as a non-classical cardiovascular risk factor in patients on maintenance hemodialysis (HD). The aim of this study was to evaluate the impact of cinacalcet on oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine), endothelial function (FMD %) and carotid artery intima-media thickness (CIMT) in HD patients. METHODS: Forty-two chronic HD patients with secondary hyperparathyroidism undergoing 60 mg/day cinacalcet treatment with a follow-up of 6 months and 38 age- and sex-matched healthy individuals were included in this prospective study. Plasma malondialdehyde (MDA) levels and 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG) were determined as oxidative stress markers. Superoxide dismutase (SOD), paraoxonase (PON), catalase (CAT), carbonic anhydrase (CAN) and glutathione peroxidase (GPx) activities were measured as antioxidants. FMD % and CIMT were assessed by ultrasonography. RESULTS: MDA levels were decreased; SOD, PON, CAT, CAN and GPx activities were increased after 6 months of cinacalcet treatment in HD patients. Although CIMT remained stabile, there was a significant improvement in FMD % as well as a notable reduction trend in 8-OHdG/dG ratio after 6 months of treatment. CONCLUSION: Our data have demonstrated that cinacalcet improves oxidative stress, genomic damage, endothelial function and increases antioxidant protection in HD patients after 6 months of treatment.

Urinary gamma-glutamyl transferase-to-creatinine ratio as an indicator of tubular function in Bence Jones proteinuria.

Increased urinary gamma-glutamyl transferase (GGT) activity suggests early renal tubular damage. The aim of this study was to evaluate the urinary GGT activity as a marker of renal injury in different types of Bence Jones Proteinuria (BJP). One hundred and three individuals with BJP were included in the study. Urinary GGT activity, urinary GGT-to-creatinine ratio and urinary protein-to-creatinine ratio were studied. Urine samples were tested by immunofixation agarose gel electrophoresis. Total urinary excretion of kappa and lambda light chains were measured by nephelometric method. There were no significant differences in demographic characteristics of the patients in Lambda BJP, Kappa BJP and Control groups. GGT-to-creatinine ratio of the Lambda BJP group was significantly higher than Kappa BJP group and controls (p = 0.018 and 0.002, respectively). There was no correlation between the quantitative kappa and lambda BJP and urinary GGT-to-creatinine ratio. Our data have demonstrated that urinary GGT-to-creatinine ratio could be a tubular damage marker of lambda light chain proteinuria.

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 lowering dialysate sodium on carotid artery atherosclerosis and endothelial dysfunction in maintenance hemodialysis patients.

PURPOSE: Our aim in this study was to examine the effects of low-sodium dialysate on carotid artery atherosclerosis, endothelial dysfunction, and blood pressure (BP) in maintenance hemodialysis (HD) patients. METHODS: After baseline measurements were obtained, the dialysate sodium concentration was reduced from 140 to 137 mEq/L. Carotid artery intima-media thickness (CIMT) and flow-mediated dilatation (FMD%) were measured before and after 6 months of HD with low-sodium dialysate. Interdialytic weight gain (IDWG), pre- and post-dialysis BP, and dialysis-related symptoms were monitored during the study. RESULTS: Fifty-two patients were enrolled, and 41 patients completed the study. Twenty-one patients had hypertension and were receiving antihypertensive medications. The average number of antihypertensive drugs per patient was 1.9±0.8. There was no significant reduction in BP at the end of the study, but the average number of antihypertensive drugs was reduced to 1.2±0.4 (P<0.001). There were significant improvements in CIMT (P=0.003) and FMD (P<0.001) with low-sodium HD. The IDWG decreased significantly during the low-sodium dialysate treatment (P<0.001). However, hypotensive episodes and cramps were more frequent during the study period. CONCLUSIONS: Our study demonstrated that the lowering of dialysate sodium concentration reduced CIMT, improved FMD, and provided better control of IDWG and BP, but increased the incidence of dialysis-related symptoms.