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.

The effects of allopurinol on metabolic acidosis and endothelial functions in chronic kidney disease patients.

BACKGROUND: Hyperuricemia and metabolic acidosis have emerged as important risk factors for progression of kidney disease. In this study, we aimed to investigate the effects of allopurinol on metabolic acidosis and endothelial functions in hyperuricemic stage 2-4 chronic kidney disease (CKD) patients. METHODS: Thirty patients with stage 2-4 CKD and serum uric acid levels over 5.5 mg/dl were included in the study group. They were prescribed 300 mg/day per oral allopurinol treatment for three months. Age- and gender-matched CKD patients (n = 30) with similar clinical characteristics were taken as the control group and were not given allopurinol treatment. Endothelial functions were measured via flow-mediated dilatation (∆FMD %) over the forearm. pH and HCO3 levels in venous blood, Cr clearance and proteinuria levels were calculated in all patients at baseline and in the third month. RESULTS: Serum uric acid levels significantly decreased in the study group from 7.9 ± 1.6 to 6.4 ± 1.7 (p < 0.001). Cr clearance (from 43.4 ± 20.1 to 51.4 ± 24.9, p = 0.011), serum bicarbonate levels (from 21.4 ± 3.4 to 23.0 ± 3.4, p = 0.007) and ΔFMD % values (from 5.8 ± 2.5 to 6.2 ± 2.7, p = 0.006) increased significantly in the allopurinol group. There were no significant changes except for ∆FMD % values (decreased from 6.27 ± 1.62 to 5.71 ± 1.90, p = 0.005) in the control group. ∆FMD % variations within the two groups were clearly significant in the repeated ANOVA general linear model. CONCLUSION: We assume that decreasing uric acid levels with allopurinol treatment seems to be helpful in restoring endothelial functions, preventing metabolic acidosis and slowing down the progression of CKD.

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.

Fibromyalgia and nondipper circadian blood pressure variability.

BACKGROUND AND OBJECTIVES: Aberrant circadian rhythm with persistent nocturnal sympathetic hyperactivity has pointed out malfunctioning autonomic nervous system in fibromyalgia (FM) patients. This is a common pathogenesis shared also by patients with nondipping blood pressure (BP) pattern. Therefore, we aimed to investigate the frequency of nondipping BP pattern in normotensive women with newly diagnosed FM compared with healthy women. METHODS: Sixty-seven normotensive women with new diagnosis of FM and 38 age-matched healthy volunteer women were recruited into the study. All subjects underwent 24-hour ambulatory BP monitoring on a usual working day. Individuals were defined as "dippers" if their nocturnal BP values decreased by more than 10% compared with daytime values; defined as "nondippers" in case of a decline less than 10%. Serum creatinine, fasting blood glucose, cholesterol levels, albumin, and thyroid-stimulating hormone levels were assessed. RESULTS: Ambulatory measurements showed significantly higher diastolic BP values in patients with FM for both average of 24-hour recordings. Patients with FM had significantly lower systolic (9.1 ± 3.9 vs 11.5 ± 4.9, P = 0.010) and diastolic dipping ratios (12.3 ± 6.1 vs 16.1 ± 6.4, P = 0.004). The number of nondippers in the FM group was significantly higher than that of controls for both systolic (66% vs 34%, P = 0.002) and diastolic BP measurements (42% vs 21%, P=0.031). Patients with FM were 3.68 times more likely to be systolic nondipper and 2.69 times more likely to be diastolic nondipper. CONCLUSIONS: We have demonstrated a significant relationship between FM and nondipping BP pattern, and we suggest that nondipping profile, which has been closely associated with cardiovascular morbidity, may appear as an additional risk factor in patients with FM.

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.

Daily dietary energy and macronutrient intake and anthropometric measurements of the peritoneal dialysis patients.

INTRODUCTION: This study was planned to investigate the relation between dietary macronutrient status and anthropometric measurements in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: A total of 28 clinically stable patients were enrolled in this study. All patients were taken a dietary therapy according to the guidelines of the American Journal of Kidney Foundation for 12 weeks. The anthropometric measurements were taken by bioelectrical impedance analyzer. The daily macronutrient intakes of the patients were calculated by the food consumption records. RESULTS: The mean age was 48.3 ± 13.10 years [56.3 ± 7.41 years for males (n = 14) and 40.3 ± 12.84 years for females (n = 14)]. There were significant changes in fat percentage (%), total body water (TBW; %, L), extracellular water (ECW; %, L), basal metabolic rate over body weight (BMR/BW), and body fat mass index (BMFI) in males (p < 0.05), but there was no change in females (p > 0.05). The daily dietary energy and protein intakes were under the recommended level in the study period. CONCLUSION: Patients undergoing PD frequently have low intakes of protein and energy. It is recommended that individuals undergoing PD periodically maintain 3-day dietary records followed by dietary interviews conducted by a dietitian.

Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease.

AIM: The current data have proven the pivotal role of inflammation in the development of atherosclerosis and cardiovascular diseases in patients with chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has increasingly been reported as a measure of systemic inflammation. This study assessed N/L ratio and investigated its associations with standard inflammatory biomarkers in different stages of CKD patients. MATERIAL AND METHODS: This cross-sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis patients, and 30 healthy subjects. N/L ratio and important clinical and laboratory parameters were registered. Multivariate regression analyses were carried out to investigate the relations of N/L ratio. RESULTS: N/L ratio was significantly higher in each patient group compared to the healthy subjects (for all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r = 0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p = 0.002) levels and negatively correlated with hemoglobin (r = -0.271, p = 0.001), serum albumin (r = -0.400, p < 0.001), and high-density lipoprotein (HDL) cholesterol levels (r = -0.302, p < 0.001). In CKD patients with hypertension (HT), higher N/L ratio was detected when compared to those without HT (p = 0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and hs-CRP levels were found to be independent predictors of the ratio after adjusting for significant covariates (p < 0.001). CONCLUSION: An easy and inexpensive laboratory measure of N/L ratio might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.

Is colchicine therapy effective in all patients with secondary amyloidosis?

OBJECTIVE: Although colchicine is effective on prevention and regression of amyloidosis in many cases, rate of unresponsiveness to colchicine therapy is not too low. However, there is no sufficient data about which factors effect to response of colchicine therapy on regression of amyloidosis. MATERIALS AND METHODS: 24 patients with renal amyloidosis were enrolled into the study. The patients were divided in two groups according to urinary protein excretions: non-nephrotic stage (14/24) and nephrotic stage (10/24). The patients were also categorized according to the etiology of amyloidosis; familial Mediterranean fever (FMF)-associated amyloidosis (15/24) versus rheumatoid disorders (RD)-associated amyloidosis (9/24). The changes of amount of proteinuria and estimated glomerular filtration rates were investigated after colchicine treatment started in these groups. RESULTS: The mean follow-up period was 27.7 ± 19.2 months. After initiating colchicine therapy, the degree of proteinuria was decreased higher than 50% in 11/14 (78%) of non-nephrotic patients and elevated only in three (22%) patients. In nephrotic group, proteinuria was increased in 5/10 (50%) of patients. Glomerular filtration rates were stable in nephrotic and non-nephrotic groups. Presenting with nephrotic syndrome was higher in RD-associated amyloidosis (RD_A) group (5/9) than FMF-associated amyloidosis (FMF_A) group (5/15) without statistical significance (p > 0.05). After colchicine treatment, proteinuria was decreased in 12/15 patients in FMF_A group, however, the significant decreasing of proteinuria was not observed in RD_A group (p = 0.05 vs. p > 0.05). CONCLUSION: Colchicine therapy was found more effective in low proteinuric stage of amyloidosis. The beneficial effect of colchicine therapy was not observed in patients with RD- associated amyloidosis.

Sunitinib- and sorafenib-induced nephrotic syndrome in a patient with gastrointestinal stromal tumor.

OBJECTIVE: To report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. CASE SUMMARY: A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. DISCUSSION: Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. CONCLUSIONS: The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.

Remission of de novo membranous nephropathy in a kidney allograft recipient: a case report.

Membranous nephropathy (MN), one of the most frequent causes of nephrotic syndrome in native kidneys, is also a common glomerular pathology in transplanted kidneys(Davison AM, Johnston PA. Allograft membranous nephropathy, Nephrol Dial Transplant, 1992;7(Suppl. 1):114-118. Specific treatment modalities have not been described for this population. However, renal transplanted patients presented with MN could have spontaneous remission as those with idiopathic MN. Here, we report a kidney allograft recipient diagnosed with de novo MN in early phases of posttransplantation period having a clinical remission over months.

Successful pregnancy in an end-stage renal disease patient on peritoneal dialysis.

Among women with chronic kidney disease, successful pregnancy with a surviving infant is rather rare. Although these pregnancies carry higher risk, with the possibility of adverse maternal and fetal outcomes, they can be managed with close monitoring and intense renal replacement therapy. Given the hemodynamic advantages of peritoneal dialysis over hemodialysis in pregnancy, peritoneal dialysis therapy is thought to be a favorable renal replacement option in pregnant patients with chronic kidney disease.

Salt intake and hypervolemia in the development of hypertension in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients are often volume-expanded and have higher-than-normal blood pressure (BP) levels. In the present study, we aimed to investigate the role of fluid balance and salt intake for BP control in our PD patients. The study included 37 patients undergoing PD and having complete data for 3 consecutive months. Patients were allocated to one of two groups based on measured BP in the preceding 3 months: hypertensive patients (BP > 140/90 mmHg) and normotensive patients (did not meet the hypertensive BP criteria). Volume status was evaluated by bioimpedance analysis. The 37 patients (18 women, 19 men) had a mean age of 46.4 years. The hypertensive and normotensive groups included 17 and 20 patients respectively. Sex, age, and time on PD were similar between the groups. Weight (77.3 +/- 20.3 kg vs. 64.5 +/- 9.8 kg, p < 0.05), total sodium load (2649.2 +/- 621.9 mmol vs. 2272.4 +/- 511.9 mmol, p < 0.05), daily total sodium removal (160.5 +/- 74.4 mmol vs. 112.1 +/- 48.0 mmol, p < 0.05), extracellular water (19.4 +/- 4.3 L vs. 16.4 +/- 3.5 L, p < 0.05), and normalized extracellular water (11.6 +/- 1.9 L vs. 10.1 +/- 1.8 L, p < 0.05) were all significantly higher in the hypertensive group. Despite higher fluid and sodium removal, hypertensive patients were more hypervolemic than normotensive patients. Increasing fluid and salt removal by peritoneal ultrafiltration results in an increased financial burden and also causes serious clinical problems. Restricting fluid and salt intake is an alternative and safer strategy to maintain good fluid balance.

Acute kidney injury due to rhabdomyolysis in H1N1 influenza infection.

Acute kidney injury (AKI) is rarely reported in the clinical course of H1N1 infection and this condition is strongly related with increasing of mortality risk. However, there are no sufficient data about the development of AKI due to H1N1 infections. The recent reports were documented for elevation of creatinine phosphokinase levels in the course of influenza infection, but rhabdomyolysis was rarely reported. Herein, we present a 28-year-old female patient and a 19-year-old male patient with AKI in the course of H1N1 influenza infection due to rhabdomyolysis.

A patient with Crohn's disease who presented with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.

Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is characterized with fever, purpura, anemia due to microangiopathic hemolysis, thrombocytopenia, kidney damage, and neurologic symptoms. The development of TTP/HUS during the course of inflammatory bowel diseases was rarely reported. However, coexistence of TTP/HUS and Crohn's disease in the same patient has not been reported previously. We herein present a case of TTP/HUS who presented with Crohn's disease. He responded to cyclosporine treatment.

Idiopathic hypoparathyroidism mimicking diffuse idiopathic skeletal hyperostosis.

Idiopathic hypoparathyroidism is an uncommon disease caused by insufficient secretion of parathyroid hormone. Idiopathic hypoparathyroidism may cause various musculoskeletal findings, including diffuse ligamentous and entheseal ossifications. Diffuse idiopathic skeletal hyperostosis is a disorder of the elderly characterized by ossification of the anterior longitudinal ligament of the spine and various extraspinal ligaments. We present a 50-year-old man with idiopathic hypoparathyroidism who had been diagnosed as having DISH at 40 years of age. Resistant neck, left shoulder, and left hip pain did not improve with calcium and calcitriol treatment after diagnosis of idiopathic hypoparathyroidism.

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.

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.