We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally). Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment. The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seedproanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index(AI)and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Acute kidney injury (AKI) is a major cause of mortality and morbidity in hospitalized patients. Incidence and mortality rates vary from country to country, and according to different in-hospital monitoring units and definitions of AKI. The aim of this study was to determine factors affecting frequency of AKI and mortality in our hospital. We retrospectively evaluated data for 1550 patients diagnosed with AKI and 788 patients meeting the Kidney Disease: Improving Global Outcomes (KDIGO) guideline AKI criteria out of a total of 174 852 patients hospitalized in our institution between January 1, 2007 and December 31, 2012. Staging was performed based on KDIGO Clinical Practice for Acute Kidney Injury and RIFLE (Risk, Injury, Failure, Loss of kidney function and End-stage renal failure). Demographic and biochemical data were recorded and correlations with mortality were assessed. The frequency of AKI in our hospital was 0.9%, with an in-hospital mortality rate of 34.6%. At multivariate analysis, diastolic blood pressure (OR 0.89, 95% CI 0.87-0.92; P < 0.001), monitoring in the intensive care unit (OR 0.18, 95% CI 0.09-0.38; P < 0.001), urine output (OR 4.00, 95% CI 2.03-7.89; P < 0.001), duration of oliguria (OR 1.51, 95% CI 1.34-1.69; P < 0.001), length of hospitalization (OR 0.83, 95% CI 0.79-0.88; P < 0.001), dialysis requirement (OR 2.30, 95% CI 1.12-4.71; P < 0.05), APACHE II score (OR 1.16, 95% CI 1.09-1.24; P < 0.001), and albumin level (OR 0.32, 95% CI 0.21-0.50; P < 0.001) were identified as independent determinants affecting mortality. Frequency of AKI and associated mortality rates in our regional reference hospital were compatible with those in the literature. This study shows that KDIGO criteria are more sensitive in determining AKI. Mortality was not correlated with staging based on RIFLE or KDIGO. Nonetheless, our identification of urine output as one of the independent determinants of mortality suggests that this parameter should be used in assessing the correlation between staging and mortality.

Objectives: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. Materials and methods: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. Conclusion: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

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The aim of this study was to evaluate the effects of adipocytokines including adiponectin, leptin, resistin, neuropeptide Y and ghrelin in chronic kidney disease (CKD) patients on appearance of protein-energy wasting (PEW). One hundred fifty patients with mean age of 45.4 ± 15.9 years, without active infections or chronic inflammatory conditions were recruited into the study. Study groups were control group (consisting of 30 healthy volunteers with normal kidney functions), hemodialysis group, predialysis group, peritoneal dialysis group and kidney transplant group. Fasting morning serum leptin, ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of the groups were measured. Anthropometric and nutritional assessments of all patients were obtained. Diagnosis of PEW was made according to definition recommended by the International Society of Renal Nutrition and Metabolism. Presence of PEW in hemodialysis (23.3%) and peritoneal dialysis (26.7%) groups were significantly higher than those of predialysis (3.3%), and transplantation (0%) groups. Adiponectin and resistin levels in predialysis, peritoneal dialysis and hemodialysis patients were significantly higher than control group (p: 0.0001). This study had given significant positive correlations between presence of PEW and serum resistin (r: 0.267, p: 0.001), and serum adiponectin levels (r: 0.349, p: 0.0001). There were no relationship between presence of PEW and ghrelin, acylated-ghrelin, neuropeptide Y, and leptin levels of the groups. CKD patients except transplant patients had higher adiponectin and resistin levels than control group. PEW was found to be linearly correlated with resistin and adiponectin. High serum resistin and adiponectin levels might have a role in development of PEW among dialysis patients.