Objective: The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Materials and methods: Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously -i.v -in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20 th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evalua ted. Results: Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. Conclusion: This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy. Arch Endocrinol Metab. 2016;60(5):443-9

Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p.) once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 μM, 75 μM and 375 μM polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B.

No abstract

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

Objective: to evaluate the nursing workload in intensive care patients with acute kidney injury (AKI). Method: A quantitative study, conducted in an intensive care unit, from April to August of 2015. The Nursing Activities Score (NAS) and Kidney Disease Improving Global Outcomes (KDIGO) were used to measure nursing workload and to classify the stage of AKI, respectively. Results: A total of 190 patients were included. Patients who developed AKI (44.2%) had higher NAS when compared to those without AKI (43.7% vs 40.7%), p <0.001. Patients with stage 1, 2 and 3 AKI showed higher NAS than those without AKI. A relationship was identifi ed between stage 2 and 3 with those without AKI (p = 0.002 and p <0.001). Conclusion: The NAS was associated with the presence of AKI, the score increased with the progression of the stages, and it was associated with AKI, stage 2 and 3. Descriptors: Workload; Intensive Care Unit; Acute Renal Injury; Nursing; Nephrology. RESUMO Objetivo: avaliar a carga de trabalho de enfermagem em pacientes de terapia intensiva com lesão renal aguda (LRA). Método: estudo quantitativo, em Unidade de Terapia Intensiva, no período de abril a agosto de 2015. O Nursing Activities Score (NAS) e o Kidney Disease Improving Global Outcomes (KDIGO) foram utilizados para medir a carga de trabalho de enfermagem e classifi car o estágio da LRA, respectivamente. Resultados: foram incluídos 190 pacientes. Os pacientes que desenvolveram LRA (44,2%) possuíam NAS superiores quando comparados aos sem LRA (43,7% vs 40,7%), p<0,001. Os pacientes com LRA nos estágios 1, 2 e 3 de LRA demonstraram NAS superiores aos sem LRA, houve relação entre os estágios 2 e 3 com os sem LRA, p=0,002 e p<0,001. Conclusão: o NAS apresentou associação com a existência de LRA, visto que seu valor aumenta com a progressão dos estágios, tendo associação com os estágios 2 e 3 de LRA. Descritores: Carga de Trabalho; Unidades de Terapia Intensiva; Lesão Renal Aguda; Enfermagem; Nefrologia. RESUMEN Objetivo: evaluar la carga de trabajo de enfermería en pacientes de cuidados intensivos con lesión renal aguda (AKI -acute kidney injury). Método: un estudio cuantitativo en la Unidad de Cuidados Intensivos en el período desde abril hasta agosto de 2015. El Nursing Activities Score (NAS) y el Kidney Disease Improving Global Outcomes (KDIGO) fueron utilizados para medir la carga de trabajo de enfermería y clasifi car el estadio de AKI, respectivamente. Resultados: en total, se incluyeron 190 pacientes. Los pacientes que desarrollaron AKI (44,2%) tenían NAS superior en comparación con los pacientes sin AKI (43,7% vs 40,7%), p<0,001. Los pacientes con AKI en los estadios 1, 2 y 3 de AKI mostraron NAS más alto que aquellos sin AKI. Hubo una relación entre los estadios 2 y 3 y los pacientes sin AKI, p=0,002 y p<0,001. Conclusión: NAS se asoció con la existencia de AKI porque su valor aumenta con la progresión de los estadios y tiene asociación con los estadios 2 y 3 de AKI.

Polymyxin B (PMB) is a cationic polypeptide antibiotic with activity against multidrug-resistant Gram-negative bacteria. PMBinduced nephrotoxicity consists of direct toxicity to the renal tubules and the release of reactive oxygen species (ROS) with oxidative damage. This study evaluated the nephroprotective effect of heme oxygenase-1 (HO-1) against PMB-induced nephrotoxicity in rats. Adult male Wistar rats, weighing 286 ؎ 12 g, were treated intraperitoneally once a day for 5 days with saline, hemin (HO-1 inducer; 10 mg/kg), zinc protoporphyrin (ZnPP) (HO-1 inhibitor; 50 mol/kg, administered before PMB on day 5), PMB (4 mg/kg), PMB plus hemin, and PMB plus ZnPP. Renal function (creatinine clearance, Jaffe method), urinary peroxides (ferrous oxidation of xylenol orange version 2 [FOX-2]), urinary thiobarbituric acid-reactive substances (TBARS), renal tissue thiols, catalase activity, and renal tissue histology were analyzed. The results showed that PMB reduced creatinine clearance (P < 0.05), with an increase in urinary peroxides and TBARS. The PMB toxicity caused a reduction in catalase activity and thiols (P < 0.05). Hemin attenuated PMB nephrotoxicity by increasing the catalase antioxidant activity (P < 0.05). The combination of PMB and ZnPP incremented the fractional interstitial area of renal tissue (P < 0.05), and acute tubular necrosis in the cortex area was also observed. This is the first study demonstrating the protective effect of HO-1 against PMB-induced nephrotoxicity.

Objective: To characterize the toxicity of polymyxin B (PmxB) in renal cell in different dosage and times. Methods: LLC-PK1 cells grown in 12 well multiwell plates were divided into the following groups: Control (CTL) -cells maintained in DMEM supplemented with 5%; G1 -cells exposed to concentration of 75µM PmxB G2 -cells exposed to concentration of 375µM PmxB. Each group was assessed at 24,48 and 72 hours as for cell viability (Acridine orange/ethidium bromide) and apoptosis (Hoechst 33342).Results: The data demonstrate the cell viability and apoptosis exposure of three doses of PmxB in three time intervals, with a significant increase in toxicity to high doses and longer duration of stay in the antibiotic to apoptosis. Conclusion: Cytotoxicity by PmxB in cell culture model, showed to be time and dose dependent, increasing with increased exposure and higher dose of antibiotic. ResumoObjetivo: Caracterizar a toxicidade da polimixina B (PmxB) em células renais em dosagem e tempos diferentes. Métodos: Células LLC-PK 1 , cultivadas em placas multiwell de 12 poços, foram divididas nos seguintes grupos: Controle (CTL) -células mantidas em meio DMEM suplementado a 5%; G1 -células expostas à concentração de 75mM de PmxB; G2 -células expostas à concentração de 375mM de PmxB. Cada grupo foi avaliado nos tempos de 24, 48 e 72 horas quanto à viabilidade celular (Acridine Orange/ Brometo de Etídio) e apoptose (Hoechst 33342). Resultados: Os dados demonstraram a viabilidade celular e a apoptose à exposição de três doses de PmxB em três intervalos de tempo, com um aumento significativo da toxicidade à elevação das doses e ao maior tempo de permanência no antibiótico para apoptose. Conclusão: A citotoxicidade pela PmxB, no modelo de cultivo celular, se mostrou tempo e dose dependente, aumentando com a maior exposição e maior dose de antibiótico.