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.

Bilateral optic neuropathy, acral gangrene and visceral ischaemia as a rare presentation of calciphylaxis: A case report.

We report a case with calciphylaxis very rarely presenting with bilateral optic neuropathy, acral gangrene and visceral ischaemia. Bilateral papilloedaema was found in a 43 year-old female with chronic renal failure. Acral dry gangrene was observed. Pathological examination of her amputated thumb revealed calcification, thrombi, obstructive endovascular fibrotic areas in the walls of arteries. She was diagnosed with calciphylaxis. Bilateral optic neuropathy was defined secondary to calciphylaxis. Abdominal computerized tomography revealed prominent calcifications in mesenteric, spleen and renal arteries. She died eight months after the diagnosis. Calciphylaxis should be considered in the differential diagnosis of the optic neuropathy.

The effectiveness of oral essential aminoacids and aminoacids containing dialysate in peritoneal dialysis.

BACKGROUND/AIM: Oral essential amino acids (AAs) containing supplements (EAS) and AA containing dialysate (ACD) are frequently used in peritoneal dialysis (PD) patients with malnutrition. The present study was conducted to investigate two strategies and compare their effects on the malnutrition status of PD patients. MATERIALS AND METHODS: A total of 31 EAS, 14 ACD patients were enrolled in this study. Serum albumin levels were lower than 3.5 g/dL in all subjects. EAS group patients took five pills containing AAs three times a day with meals. In the other, 2.000 cc of 1.1% ACD was given to patients daily during the study. Demographic and laboratory parameters were analyzed and compared at baseline and 6th month. RESULTS: Significant increases in BMI, albumin, and protein in both groups. Mean albumin levels increased significantly by 0.54 g/dL in ACD group (p < 0.005) and 0.49 g/dL in EAS group (p < 0.001) following 6 months. Mean albumin and delta albumin levels did not differ between two groups. CONCLUSION: These strategies may play an important role in increasing albumin levels and improving the nutritional status of PD patients.

The effects of L-carnitine therapy on respiratory function tests in chronic hemodialysis patients.

BACKGROUND: Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy. METHODS: A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months. RESULTS: The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p < 0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 +/- 12.15 and 83.00 +/- 14.49, before and after treatment, respectively, p < 0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25-75% of expired vital capacity were not significant in the treatment group (p > 0.05). CONCLUSION: Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

The effect of dietary ginger (Zingiber officinals Rosc) on renal ischemia/reperfusion injury in rat kidneys.

Oxidative stress has been considered as one of the possible mechanisms of ischemia/ reperfusion (I/R) injury in the kidney. The aim of this study was to analyze the possible protective effect of dietary ginger (Zingiber officinals Rosc), a free radical scavenger, on renal I/R injury in rats. The protective effect of ginger against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Thirty rats were randomly divided into five experimental groups (i.e., control, sham-operated, ginger, I/R, and I/R + ginger groups, n = 6 each). The ginger and I/R + ginger groups were fed on the test diet containing 5% ginger. The rats were subjected to bilateral renal ischemia followed by reperfusion in I/R and I/R + ginger groups. At the end of the reperfusion period, rats were sacrificed, and kidney function tests, serum and tissue oxidants and antioxidants, and renal morphology were evaluated. Serum urea, creatinine, and cystatin C (CYC) levels were significantly elevated in the ischemia group, but these levels remained unchanged in the ginger + I/R group compared to the I/R group. Reduction of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activity was significantly improved by the treatment with ginger compared to I/R group. Administration of ginger resulted in significant reduction levels of tissue malondialdehyde (MDA), NO, protein carbonyl contents (PCC) in the ginger + I/R group compared with the I/R group. Ginger supplementation in the diet before I/R injury resulted in higher total antioxidant capacity (TAC) and lower total oxidant status (TOS) levels than I/R group. The ginger supplemented diet prior to I/R process demonstrated marked reduction of the histological features of renal injury. The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.

Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: an experimental model.

Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.

Association of obesity with inflammation in occult chronic kidney disease.

BACKGROUND: There are few studies concerning the development of chronic kidney disease (CKD) in obese patients independent of its relation with other risk factors. Also, the role of inflammation in this relationship is unclear. In this study we aimed to test the hypothesis that obesity is associated with risk for CKD and whether this risk is associated with serum C-reactive protein (CRP) levels in an apparently healthy obese population. METHODS: Biochemical parameters and urinary protein excretion were determined in 110 patients with body mass index (BMI) >30.0 (calculated as kg/m2) and 50 age-matched healthy controls. Glomerular filtration rate was estimated by calculation of creatinine clearance. RESULTS: Of the patients, 17.3% had CKD. They had higher CRP levels than controls (6.52 +/- 0.58 mg/L and 4.48 +/- 1.26 mg/L, respectively, p=0.001). Furthermore, CRP levels were positively correlated with BMI, waist circumference, waist to hip ratio and proteinuria, and negatively correlated with glomerular filtration rate (GFR). When GFR was considered as the dependent variable in a multiple regression analysis, CRP maintained its significant correlation with GFR. CONCLUSION: Our study of apparently healthy obese individuals, has shown a significant association between BMI and CKD independent of other potential mediators. Furthermore, our findings suggest that inflammation may be the pathogenic mechanism of obesity-related CKD.

Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis.

BACKGROUND: The atherosclerotic process progresses more dynamically in hemodialysis (HD) patients than in the general population. In HD patients, lower magnesium levels were reported to be associated with increased atherosclerosis of the common carotid artery. We tested the hypotheses that magnesium supplementation helps to improve carotid intima media thickness (IMT) in HD patients. MATERIALS AND METHODS: A total of 47 patients on HD were included in the study. Patients were randomly divided into two groups: group A (Mg group), in which patients were given magnesium citrate orally at a dosage of 610 mg every other day for 2 months and group B (control group), in which patients received only calcium acetate therapy as a phosphate binder. At baseline and 2 months later, all patients underwent a carotid artery ultrasound scan to measure carotid IMT. RESULTS: At the end of 2 months, mean serum calcium, phosphorus, and calcium x phosphorus product were not changed in both groups. As expected, mean serum Mg level significantly increased in the Mg group at the end of 2 months. In addition, serum parathyroid hormone (PTH) level significantly decreased in the Mg group at the end of 2 months (P = 0.003). Baseline carotid IMT was similar between the groups. Bilateral carotid IMT was significantly improved in patients treated with magnesium citrate compared to initial values (P = 0.001 for left, P = 0.002 for right). CONCLUSION: Based on the present data, magnesium may play an important protective role in the progression of atherosclerosis in patients on dialysis. Further studies are needed to assess more accurately the role of magnesium in atherosclerotic regression in dialysis patients.

Relation between serum calcium, phosphate, parathyroid hormone and 'nondipper' circadian blood pressure variability profile in patients with normal renal function.

BACKGROUND AND AIMS: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium x phosphate (Ca x P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. METHODS: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. RESULTS: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 +/- 0.61 vs. 3.35 +/- 0.44 mg/dl, p = 0.001), Ca x P product (35.4 +/- 6.5 vs. 31.5 +/- 5.0, p = 0.001) and PTH (75.7 +/- 28.8 vs. 46.6 +/- 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (beta = 0.43, p = 0.001) and phosphate (beta = 0.9, p = 0.03). CONCLUSION: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca x P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.

The protective effect of erdosteine against cyclosporine A-induced cardiotoxicity in rats.

Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection and in the treatment of autoimmune diseases. However, CsA generates reactive oxygen species, which causes nephrotoxicity, hepatotoxicity and cardiotoxicity. The use of antioxidants reduces the adverse effects of CsA. The aim of this study is to determine the protective effects of erdosteine on CsA-induced heart injury through tissue oxidant/antioxidant parameters and light microscopic evaluation in rats. CsA cardiotoxicity was induced by administrating an oral dose of 15mg/kg CsA daily for 21 days. The rats were divided into four groups: control group (n=4), CsA administrated group (15mg/kg, n=5), CsA+erdosteine administrated group (10mg/kg day orally erdosteine, n=4) and only erdosteine administrated group (10mg/kg day orally n=5). CsA treated rats showed increase in the number of infiltrated cells and disorganization of myocardial fibers with interstitial fibrosis. The number of infiltrated cells, disorganization of myocardial fibers and interstitial fibrosis was diminished in the hearts of CsA-treated rats given erdosteine. The malondialdehyde, the protein carbonyl content and nitric oxide levels were increased in the cyclosporine A group in comparison with the control and CsA plus erdosteine groups. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were higher in CsA plus erdosteine group than CsA group. However, the CAT, GSH-Px and SOD activities were significantly lower in CsA group than in control group and erdosteine group. These results suggest that erdosteine has protective effect against CsA-induced cardiotoxicity.

Serum BNP concentration and left ventricular mass in CAPD and automated peritoneal dialysis patients.

OBJECTIVE: To compare ultrafiltration under continuous ambulatory peritoneal dialysis (CAPD) and automated PD (APD), disclosing potential effects on serum B-type natriuretic peptide (BNP) levels and echocardiographic findings. PATIENTS AND METHODS: This cross-sectional clinical study included 32 patients on CAPD and 30 patients on APD without clinical evidence of heart failure or hemodynamically significant valvular heart disease. Peritoneal equilibration tests, BNP levels, and echocardiographic measurements were performed in each subject. BNP measurements were also performed in 24 healthy control subjects. RESULTS: Patients on APD had lower ultrafiltration and higher values of BNP and left ventricular mass index (LVMI) compared with patients on CAPD (respectively: 775 +/- 160 vs 850 +/- 265 mL, p = 0.01; 253.23 +/- 81.64 vs 109.42 +/- 25.63 pg/mL, p = 0.001; 185.12 +/- 63.50 vs 129.30 +/- 40.95 g/m(2), p = 0.001). This occurred despite higher mean dialysate glucose concentrations and far more extensive use of icodextrin in the APD group. CONCLUSION: Treatment with APD is associated with higher plasma BNP levels and LVMI compared to CAPD. This may be the result of chronic fluid retention caused by lower ultrafiltration in APD patients.

Cefuroxime-induced lupus.

Drug-induced lupus erythematosus (DILE) is a syndrome that shares symptoms and laboratory characteristics with idiopathic systemic lupus erythematosus. Recognition of DILE is important because it usually reverts within a few weeks after stopping the offending drug. Antibiotics are uncommonly associated with DILE, and cefuroxime has never been incriminated as a cause. We present herein the first case of DILE induced by cefuroxime. Although this is the first report of cefuroxime-induced DILE, we should be aware of this occurrence.

Comparison of effects of darbepoetin alfa and epoetin alfa on serum endothelin level and blood pressure.

It is well known that epoetin alfa increases serum endothelin (ET)-1 and blood pressure. No data are available, however, on the effects of darbepoetin alfa on serum ET-1 and blood pressure. This study was conducted to compare the effects of darbepoetin alfa and epoetin alfa on serum ET-1 and blood pressure in patients on hemodialysis (HD). A total of 42 patients on HD were included in the study. Serum samples for measuring levels of ET-1 were taken 30 min after administration of epoetin alfa. After blood samples had been taken from all patients, epoetin alfa was changed to darbepoetin alfa. Three months after the start of darbepoetin alfa treatment, blood samples were taken to measure the same parameters. Mean arterial blood pressure was measured before recombinant human erythropoietin (EPO) administration and 30 min after EPO administration while patients were taking epoetin alfa or darbepoetin alfa. Injection of epoetin alfa or darbepoetin alfa significantly increased serum ET-1 levels compared with levels in those patients who were not on EPO therapy (P<.05). When the effects of epoetin alfa on serum ET-1 level were compared with those of darbepoetin alfa, the 2 types of EPO were found to increase serum ET-1 levels similarly (P>.05). Administration of epoetin alfa or darbepoetin alfa increased systolic and diastolic blood pressures significantly over values in the control group (P<.05). Serum systolic and diastolic blood pressures increased similarly after injection of epoetin alfa or darbepoetin alfa. Administration of darbepoetin alfa increased blood pressure in patients on HD in a way that was positively correlated with enhanced ET-1 release; a similar correlation was noted with epoetin alfa.

Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions.

BACKGROUND: Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR) >60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function. MATERIALS AND METHODS: Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients' serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment. RESULTS: A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P < 0.05). However, urine protein excretion remained unchanged (P > 0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P > 0.05). CONCLUSION: We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.

Evaluation of Intraocular Pressure by Ocular Response Analyzer in Patients Undergoing Hemodialysis.

PURPOSE: The aim of this study was to compare the biomechanical parameters of the cornea and intraocular pressure (IOP) before and after hemodialysis (HD) in patients with end-stage renal disease (ESRD) and also healthy subjects. MATERIALS AND METHODS: Twenty-one patients with ESRD undergoing HD treatment (study group) and 21 healthy individuals (control group) were enrolled in this prospective study. Right eyes of each subjects were included. Central corneal thickness (CCT) were measured using Sirius Scheimpflug camera. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated IOP (IOPcc), and Goldmann-related IOP (IOPg) were measured using ocular response analyzer. In the study group, measurements were taken just before HD and 30 minutes after HD. RESULTS: The mean CCT, CRF, IOPg values did not differ between pre-HD, post-HD, and controls (P > 0.05). CH was found to be significantly higher in control group (10.6 ± 1.2 mm Hg) when compared with pre-HD (8.07 ± 1.8 mm Hg) and post-HD (8.8 ± 1.6 mm Hg) CH values (P = 0.0001). The mean IOPcc values did not differ pre-HD (18.5 ± 3.5 mm Hg) and post-HD (17.8 ± 3.9 mm Hg) (P = 0.39). The mean IOPcc values were lower significantly in control group (15.4 ± 2.8 mm Hg) when compared with pre-HD and post-HD values (P = 0.02 and 0.02, respectively). Significant correlations were seen between post-HD CRF and post-HD CCT (r = 0.6, P = 0.03); and post-HD IOPg and post-HD CCT (r = 0.51, P = 0.01). CONCLUSIONS: ESRD may disrupt the biomechanical properties of the cornea. Changes in ocular response analyzer parameters should be kept in mind to evaluate accurate IOP measurements in patients with ESRD.

Hemostatic alterations in fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver failure. Whatever its cause, the liver failure is accompanied by multiple changes in the hemostatic system. The objective of the current report was to study several homeostasis parameters such as protein C, protein S, factor 7, factor 8 levels, platelet counts, prothrombin time and activated partial thromboplastin time, and plasminogen activator inhibitor in patients with fatty liver. A total of 28 consecutive patients with ultrasound proven NAFLD and 33 healthy volunteers were included in the study. Plasma prothrombin time and activated partial thromboplastin time were within normal ranges in both NAFLD and control groups. Plasma factor 7, factor 8, protein S, and protein C levels were decreased in NAFLD patients but the difference was not statistically significant, whereas plasminogen activator inhibitor 1 levels were significantly increased in patients with NAFLD compared to controls. In conclusion, in all types of liver disease, some alterations in hemostatic parameters are awaited. As fatty liver disease is very common in clinical practice, clinicians should be aware of this kind of alterations.