Manganese superoxide dismutase, glutathione peroxidase and catalase gene polymorphisms and clinical outcomes in acute kidney injury.

INTRODUCTION: The aim of this study was to evaluate the potential association of single gene polymorphisms of manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1) and catalase (CAT) with clinical outcomes of acute kidney injury (AKI). MATERIALS AND METHODS: Ninety AKI patients and 101 healthy volunteers were included in the study. Determination of MnSOD rs4880, GPX1 rs1050450 and CAT rs769217 polymorphisms was performed using real-time polymerase chain reaction amplification. The duration of hospitalization of AKI patients, dialysis and intensive care requirements, sepsis, oliguria and in-hospital mortality rates were assessed. RESULTS: The MnSOD, GPX1 and CAT genotypes and allele frequencies of AKI patients did not differ significantly from those of healthy controls. In patients with a T allele in the ninth exon of the CAT gene, intensive care requirements were greater than those of patients with the CC genotype (p = 0.04). In addition, sepsis and in-hospital mortality were observed significantly more frequently in patients with a T allele in the ninth exon of the CAT gene (p = 0.03). Logistic regression analysis determined that bearing a T allele was the primary determinant of intensive care requirements and in-hospital mortality, independent of patient age, gender, presence of diabetes and dialysis requirements (OR 6.10, 95% CI 1.34-27.81, p = 0.02 and OR 10.25, 95% CI 1.13-92.80, p = 0.04, respectively). CONCLUSION: Among AKI patients in the Turkish population, hospital morbidity and mortality were found to be more frequent in patients bearing a T allele of the rs769217 polymorphism of the CAT gene.

Effect of cholecalciferol replacement on vascular calcification and left ventricular mass index in dialysis patients.

OBJECTIVE: The aim of this study was to determine the effect of oral cholecalciferol treatment on vascular calcification, left ventricular mass index (LVMI) and other cardiac functions in dialysis patients. DESIGN AND METHODS: A six-month course of oral cholecalciferol treatment was recommended to dialysis patients with vitamin D insufficiency. While 26 patients were given cholecalciferol treatment, 17 patients who could not tolerate to therapy received standard therapy. Initial biochemical parameters were measured, and they were measured again after 6 months of treatment. Echocardiographic measurements were also performed, and the vascular calcification score (VCS) was calculated at baseline and at the 6th month. RESULTS: The cholecalciferol replacement group showed no significant change in LVMI and VCS values (p > 0.05). However, while LVMI was similar between groups at initial evaluation, it was lower in the cholecalciferol group at the 6th month when compared to the standard treatment group (141.8 ± 40.2 g/m(2) vs. 166.3 ± 31.4 g/m(2); p = 0.04). Likewise, left ventricular diastolic diameters (48.8 ± 5.1 mm vs. 47.5 ± 4.6 mm; p = 0.023) and left atrial diameters (41.2 ± 8.9 mm vs. 38.9 ± 8.1 mm; p = 0.006) decreased in the cholecalciferol group. Additionally, significant increases were observed in serum 25-hydroxyvitamin D (25(OH)D) and albumin levels, with a significant decrease in serum C-reactive protein levels. CONCLUSION: A lesser increase in left ventricular mass and better diastolic functions was observed in dialysis patients after 6 months of cholecalciferol treatment.

The effect of biocompatible peritoneal dialysis solutions on neutrophil to lymphocyte ratio.

INTRODUCTION: Long-term exposure to dialysis solutions is an important contributor to the ongoing inflammatory process in peritoneal dialysis (PD) patients. Some studies have shown amelioration of this adverse effect with biocompatible solutions. We aimed to compare the neutrophil-to-lymphocyte (N/L) ratio in PD patients using biocompatible and standard solutions and to find out the association between N/L ratio and peritonitis indices. MATERIALS AND METHODS: This was a cross-sectional, multicenter study involving 120 prevalent PD patients. Seventy-one patients (59%) were using biocompatible solutions and 49 patients (41%) were using standard solutions. From blood samples, N/L ratio and platelet-to-lymphocyte ratio were calculated and mean platelet volume, erythrocyte sedimentation rate and hs-CRP values were detected. Data regarding the peritonitis rate and time to first peritonitis episode were also recorded. RESULTS: Biocompatible and standard groups were similar regarding age and gender. N/L ratio and hs-CRP levels have been found significantly higher in patients using biocompatible solutions (3.75 ± 1.50 vs. 3.27 ± 1.3, p = 0.04 and 3.2 ± 2.5 vs. 1.8 ± 2.0, p < 0.01, respectively). Peritonitis rates and time to the first peritonitis episode were found similar in patients using both types of solutions (0.23 ± 0.35 vs. 0.27 ± 0.32, p = 0.36 and 32.8 ± 35.8 vs. 21.5 ± 26.9 months, p = 0.16, respectively). DISCUSSION: N/L ratio was significantly higher in biocompatible solution users in parallel to hs-CRP levels, so biocompatible solutions seem to be related with increased inflammation in PD patients. Although we cannot make a certain explanation, we assume that there may be an association between acidity of the peritoneal content and virulence of microorganisms.

Utility of serum creatinine/cystatin C ratio in diagnosis of postrenal acute kidney injury.

BACKGROUND: In obstructive uropathy, despite a severe increase in the serum creatinine (Cr) levels, only a mild cystatin C (CysC) increase was previously reported. Therefore, we aimed to determine the availability of serum Cr/CysC ratio in predicting postrenal acute kidney injury (AKI). MATERIALS AND METHODS: This was a cross-sectional study involving 61-adult patients with heterogeneous AKI cases. Patients with bilateral pelvicalyceal dilatation in renal sonography were considered as postrenal AKI group (n = 15) and others were intrinsic AKI group (n = 46). Venous blood sampling for blood urea nitrogen, Cr and CysC measurements were performed on admission. RESULTS: The mean age of study population was 66.3 ± 15.5 years; 38 (62%) of which were male. Two groups were similar regarding age, gender, and comorbidities. Cr/CysC ratio was significantly higher in postrenal AKI group (6.9 ± 3.1 vs. 4.4 ± 2.1, P = 0.007). CONCLUSION: We suggest that serum Cr/CysC ratio seems to be a useful diagnostic tool for detection of postrenal AKI cases, especially for the cases without definite hydronephrosis.

Nebivolol protects erectile functions compared to Metoprolol in hypertensive men with atherogenic, venogenic, psychogenic erectile dysfunction: A prospective, randomized, cross-over, clinical trial.

INTRODUCTION: Both hypertension and ß-blocker drugs used for treating hypertension (HT) can cause erectile dysfunction (ED). Nebivolol, unlike other ß-blockers, may not cause impotence since it increases the release of Nitric Oxide (NO), which is the main mediator of erection. This study investigated the effect of Nebivolol and Metoprolol on erectile functions in hypertensive men. MATERIALS AND METHODS: Married men whose blood pressure were >140/90 mmHg were included in the study. All patients were assessed for ED, and the cause of ED was then investigated. Nebivolol or Metoprolol was started for one month in all patients. After one-month drugless period, the ß-blockers were switched. Blood pressures, pulses and sexual function tests were evaluated, and plasma NO levels were measured at the end of the treatments and during the drugless period. RESULTS: There was no difference in antihypertensive efficacy between the two drugs (p = 0.828;0.194 for systolic and diastolic BP). Metoprolol caused a significant decrease in IIEF-5 score, whereas Nebivolol did not cause a decrease in IIEF-5 score on patients with psychogenic, arteriogenic, and venous failure related ED (respectively, p<0.001,0.004,0.005 for Metoprolol; p = 0.201,0.598,0.088 for Nebivolol). In the non-ED group, both drugs decreased the IIEF-5 score, but the decrease for Metoprolol (p = 0.001) was more than that for Nebivolol (p = 0.012). Plasma NO levels did not change with Metoprolol (p = 0.268) but increased with Nebivolol (p<0.001). There was a positive correlation between plasma NO values and IIEF-5 score used for the assessment of sexual functions (r = 0.284, p = 0.026). CONCLUSION: Nebivolol may be advantageous in terms of preserving sexual functions because of increasing NO in eligible hypertensive male patients.

The role of carnitine in preventing renal damage developed as a result of infrarenal aortic ischemia-reperfusion.

BACKGROUND: This study was designed to use carnitine for preventing deposition of end products of lipid peroxidation in rat models in the prevention of ischemia-reperfusion (IR) damage frequently seen following operations of infrarenal abdominal aorta (AA). METHODS: Forty male rats of Sprague-Dawley type were evenly (n = 8) randomized to five groups: sham laparotomy (SHAM), carnitine control (CC), aortic IR (AIR), AIR + low-dose carnitine (AIR+LDC), and AIR + high-dose carnitine (AIR+HDC). RESULTS: Compared to other groups, serum creatinine levels of AIR group were significantly higher. Also tissue malondialdehyde (MDA) levels of AIR group were significantly higher compared to SHAM, CC, and AIR+HDC groups. In histopathological examination, although tubular necrosis atrophy and tubular degeneration observed in AIR group showed regression with low-dose carnitine, tubular necrosis atrophy, tubular degeneration, glomerular damage, and vascular congestion thrombosis decreased with high-dose carnitine. Total score of histological damage was significantly higher in AIR, AIR+LDC, and AIR+HDC groups compared to SHAM and CC groups. Moreover, total score of histological damage was significantly lower in AIR+HDC group than AIR+LDC group. CONCLUSIONS: In this study, we showed carnitine can partially prevent renal damage in infrarenal AIR models of rats. This result may open new prospects to us in the prevention of renal IR damage during surgery of aorta.

Malnutrition-inflammation score and endothelial dysfunction in hemodialysis patients.

OBJECTIVE: The aim of this study was to find out the relationship between Malnutrition-Inflammation score (MIS) and the endothelial function parameters, including measurements of flow-mediated vasodilatation (FMD) in the brachial artery and serum vascular cell adhesion molecule-1 (VCAM-1). Furthermore, predictors of FMD were also assessed. MATERIALS AND METHODS: A total of 70 anuric hemodialysis patients were enrolled in this cross-sectional study. Measurements of FMD, serum VCAM-1, oxidized low density lipoprotein cholesterol (oxLDL) were done before the mid-week dialysis session from all participants at the time of MIS calculation. Patients were divided into 3 groups according to MIS (the MIS was ≤4 in group I, 4< and ≤7 in group II, and >7 in group III) and compared for above parameters. RESULTS: Patients with higher MIS had higher serum high sensitive C-reactive protein, oxLDL and VCAM-1 levels whereas these patients had lower serum albumin, hemoglobin levels, and FMD rates. MIS was positively correlated with high sensitive C-reactive protein, oxLDL and VCAM-1 levels. However, there was a negative correlation between MIS and FMD. MIS and oxLDL were found as an independent significant predictors of FMD (P = .014 and P = .018, respectively) in a multivariate analysis. CONCLUSIONS: MIS is a useful tool in prediction of the severity of endothelial dysfunction. Furthermore, decrease in MIS by the modifiable parameters and also treatment of oxLDL could be expected to improve endothelial dysfunction in hemodialysis patients.

Relevance of nutritional route and intercellular adhesion molecule-1 in patients with acute renal failure and its prognostic implications.

OBJECTIVE: Nutritional support and the route of nutrition are important conditions for patients with acute renal failure (ARF) in intensive care units (ICUs). Enteral nutrition (EN) is the primary route of nutrition in these patients because of a lower rate of complications. A lack of enteral feeding was reported to increase intercellular adhesion molecule-1 (ICAM-1) in experimental models. Serum soluble ICAM-1 (sICAM-1) level is an independent predictor of mortality in predialysis patients. However, the effect of nutritional route on serum ICAM-1 level is unknown in ARF patients. The aim of this study was to investigate the relationship between route of nutrition and serum ICAM-1 level and its prognostic implications in ICU ARF patients. METHODS: In total, 64 ICU patients with ARF were assessed according to their clinical features, route of nutrition, laboratory parameters, serum sICAM-1 levels, presence of infection, Acute Physiology and Chronic Health Evaluation (APACHE) III scores, and outcomes on their first nephrology consultation day. RESULTS: Thirty-two patients died during the follow-up period. The mortality rate and infection rate were higher in the parenteral nutrition (PN) group compared with the EN group (64% vs 42%, P = .05, and 84% vs 64%, P = .05, respectively). The route of nutrition influenced the serum sICAM-1 level. Parenteral nutrition was associated with a higher serum sICAM-1 level compared to EN (434 ng/mL [range 255 to 1,240] vs 217 ng/mL [range 123 to 296], respectively, P = .0004). The APACHE III score was found to be an independent prognostic factor among the parameters of nutritional route, presence of infection, serum albumin level, and serum sICAM-1 level. CONCLUSIONS: Patients with ARF as supported by PN had a lower serum albumin level, and a higher APACHE III score, sICAM-1 level, and mortality and infection rate. Serum sICAM-1 levels did not independently predict mortality in the present set of ARF patients.

Telomerase activity in patients with stage 2-5D chronic kidney disease.

BACKGROUND: Molecular mechanisms of increased cardiovascular mortality in chronic kidney disease (CKD) associated with biological age are not well understood. Recent studies support the hypothesis that common factors responsible for this phenomenon are cellular aging and telomere dysfunction. OBJECTIVES: The purpose of this study was to investigate the relation between telomerase activity and CKD stages. METHODS: The study included 120 patients who were followed-up for CKD stage 2-5D, composed of 30 patients of each stage and 30 healthy volunteers without any known disease who were admitted to our hospital for routine check-ups. Telomerase activity in peripheral blood mononuclear cells (PBMC) was measured using the TRAP assay. RESULTS: A significant difference was observed for telomerase activity in PBMC between groups. The detected levels were lowest in the healthy control group (0.15±0.02), and highest in CKD stage 5D patients (0.23±0.04). In CKD patients, telomerase activity in PBMC was positively correlated with the CKD stage, serum creatinine, potassium and parathormone levels, and negatively correlated with estimated glomerular filtration rate (eGFR), body mass index (BMI), platelet count and serum calcium levels. According to the linear regression analysis, independent predictors for high telomerase activity in CKD patients were eGFR and BMI. CONCLUSION: Telomerase activity in PBMC increases with advancing CKD stage in CKD patients. Increased telomerase activity in PBMC is associated with eGFR and BMI.

Predictors of mortality in patients with acute renal failure.

Mortality associated with acute renal failure (ARF) remains high despite of developments in therapy strategies and definition of different prognostic factors. Therefore, this study focused on to define new prognostic factors and especially regional characteristics of the ARF patients. One hundred fifteen ARF patients, diagnosed from November 1998 to May 2003, were included to this prospective and observational study. Clinical features, laboratory parameters, Acute Physiology and Chronic Health Evaluation (APACHE) III scores and co-morbid conditions of the patients were examined. Clinical and laboratory data, and APACHE III scores were recorded at the first nephrology consult day. Thirty of the patients (26%) died. APACHE III scores, presence and the total number of co-morbid conditions and serum albumin levels at the time of first nephrology consultation were found as independent predictors of mortality. There was a negative correlation between APACHE III scores and serum albumin levels. Not only increased APACHE III score and presence of co-morbid conditions but also low serum albumin level was found as the predictors of mortality. However, only serum albumin level is seen as modifiable prognostic factor among these parameters. Therefore, further studies are necessary to determine the causes of hypoalbuminemia in patients with ARF and the effect of it's effective treatment on patients outcome.

Sexual dysfunction in dialysis patients: does vitamin D deficiency have a role?

INTRODUCTION: Sexual dysfunction and vitamin D deficiency are highly prevalent in dialysis patients. Low levels of vitamin D have been linked to many diseases. To the best of our knowledge, the relationship between vitamin D and sexual dysfunction in dialysis patients has not been previously reported in the literature. MATERIALS AND METHODS: Cholecalciferol, 50,000 IU/week, was orally administered to 37 dialysis patients with vitamin D insufficiency for 3 months followed by dosage of 10,000 IU every other week for 3 months. The Arizona Sexual Experiences Scale (ASEX), Hospital Anxiety and Depression Scale and Pittsburgh Sleep Quality Index questionnaires were filled out by all patients at baseline and at the sixth month of the study. RESULTS: Sexual dysfunction, poor sleep quality, anxiety and depression rates were 83.7%, 45.9%, 18.9% and 48.6%, respectively in all patients. ASEX total score was found to be positively correlated with age and was negatively correlated with serum 25(OH)D level and serum albumin level. After cholecalciferol treatment, 25(OH)D levels increased significantly, however no significant change was observed in any of the parameters. In multivariate linear regression analysis, age and 25(OH)D level were found to be independent predictors of ASEX total score. CONCLUSIONS: Vitamin D deficiency seems to contribute to sexual dysfunction in dialysis patients. However, it was observed in this study that; cholecalciferol replacement given to dialysis patients with vitamin D insufficiency did not result in any significant changes in sexual functions.

Caffeic acid phenethyl ester protects against amphotericin B induced nephrotoxicity in rat model.

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 µmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 µmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models.

Short-term effect of simvastatin treatment on inflammatory parameters in peritoneal dialysis patients.

OBJECTIVE: Increased serum pro-inflammatory cytokine levels are associated with an increased mortality rate in end-stage renal disease (ESRD) patients. Statins decrease cardiovascular mortality and serum C-reactive protein (CRP) levels in hemodialysis patients. As the anti-inflammatory effect of statins has not previously been studied in peritoneal dialysis (PD) patients with a non-inflammatory status, we wanted to investigate the anti-inflammatory effect of simvastatin in these patients. MATERIAL AND METHODS: Forty-eight PD patients were randomly allocated to either simvastatin treatment (n=25) or placebo (n=23). Patients in the active-treatment group received simvastatin 20 mg/day for 1 month. At baseline and after 1 month of treatment, blood samples were drawn and high-sensitivity CRP, interleukin-6, tumor necrosis factor (TNF)-alpha and plasma lipid profiles were determined. These parameters were compared between the groups at baseline and at the end of the study period. RESULTS: Twenty-five subjects in the treatment group and 20 in the placebo group completed the study. Three patients in the placebo group were excluded from the study due to the occurrence of bacterial peritonitis during the study period. Clinical characteristics and baseline parameters were similar in both groups. Serum total and low-density lipoprotein cholesterol levels, and triglyceride and serum TNF-alpha levels decreased significantly compared to baseline in the treatment group; there were no corresponding differences in the placebo group. CONCLUSIONS: Simvastatin decreased the serum TNF-alpha level in PD patients with a non-inflammatory status. A decrease in the TNF-alpha level could be one of the possible mechanisms of the anti-atherogeneic effect of simvastatin. We suggest that different treatment strategies aimed at decreasing serum cytokine levels could be evaluated to decrease cardiovascular morbidity and mortality in the dialysis population.