Glucose-insulin infusion reduces kidney injury in an experimental model of ischemic nephropathy.

BACKGROUND/AIMS: intensive insulin therapy may reduce renal dysfunction during severe illness in adult patients. We evaluated the effects of insulin-glucose (IG) in normoglycemic rats subjected to ischemia-reperfusion (I/R)-induced acute kidney injury. METHODS: animals received intravenous infusions of 5% glucose [control (C)] or IG for 96 h. I/R was induced by means of bilateral renal artery clamping for 45 min. Serum creatinine (sCr) and urea (sUr) levels were evaluated before and up to 72 h after injury. Tissue samples were evaluated 72 h after I/R on a scale of 0 (normal) to 4 (above 75%) in relation to the extent of kidney injury. RESULTS: after 48 h of I/R, sCr and sUr were increased 2- to 4-fold in C as compared to sham-operated controls (p < 0.05). IG produced significant improvements in renal function (p < 0.05). Upon histopathological analysis, the IG group presented less tubular damage in comparison to the C group: level 1, 60 versus 20%; level 2, 20 versus 30%; level 3, 20 versus 30%, and level 4, 0 versus 20%, respectively (n = 10; p = 0.057). CONCLUSION: our results suggest that IG infusion attenuates the renal damage induced by severe I/R independently of blood glucose control. This strategy may constitute a therapeutic option for the prevention and treatment of ischemic renal injury.

Preconditioning by aerobic exercise reduces acute ischemic renal injury in rats.

Acute kidney injury (AKI) can be defined as the sudden loss of renal function associated with structural changes in the kidneys. Currently, 13.3 million people die of AKI around the world. Normally aerobic exercise is used both as/for the treatment and prevention of high blood pressure, metabolic disease and Diabetes mellitus (DM). Nevertheless, exercise preconditioning must be a crucial resource in the prevention and mitigation of AKI. The aim of this study was to evaluate the effects of the exercise preconditioning on renal IR (ischemic/reperfusion) experimental model. Male Wistars rats were divided into three groups (n = 9): sham (S), ischemic/reperfusion (IR), exercise + ischemic/reperfusion (EX + IR). IR renal injury was induced by clamping the bilateral renal artery for 45 min. The rats were subjected to exercise 5 days a week for 4 weeks with progressive intensity and duration. The group treated with exercise preconditioning, showed additional improvements in various parameters, including serum creatinine, proteinuria, and decrease of the severity of the tubular injury and activated caspase-3 levels (P < 0.05). The previous aerobic exercise-induced renoprotection in the IR injury. We anticipate that the practice of physical exercise in healthy individuals can also be useful for the prevention and attenuation of AKI.

Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice.

Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.

Medullary nephritis in the diagnosis of acute cellular rejection.

BACKGROUND: The purpose of this study was to understand the role of lymphomononuclear inflammation (nephritis) in the renal allograft medulla of transplant recipients with acute dysfunction, by comparing the immunophenotype of inflammatory cells present in the medulla and cortex of kidney graft biopsies. METHOD: This is a retrospective study of 113 renal allograft needle biopsies, presenting with medullary nephritis, divided into two groups according to the main location of nephritis: in cortical and medullary regions (corticomedullary nephritis) or exclusively in the medullary region (medullary nephritis). We performed immunohistochemistry (IHC) of the cells composing the inflammatory foci, using anti-CD4, CD8, CD20, CD68, and CD138 antibodies, respectively for T-helper cells, cytotoxic T cells, B lymphocytes, macrophages and plasmocytes. The clinical follow-up of the patients was correlated with the morphological findings. RESULTS: The nephritis was corticomedullary in 66 of the 113 cases (58.4%) and exclusively medullary in the remaining 47 cases (41.6%). The immunophenotype of the inflammatory cells was similar in the cortical and medullary compartments and were mainly: cytotoxic T lymphocytes (CD8) and macrophages CD68. The immunosuppressive therapeutic response to acute cellular rejection (ACR), based on decreasing of serum creatinine values, was 81.8% in the patients of the corticomedullary nephritis group and 63.6% in those of the medullary nephritis group. CONCLUSION: Medullary nephritis in renal allograft biopsies may indicate ACR, as could be noted by the immunophenotype, which presented the same cellular mediators of rejection seen in the allograft cortex, and by the positive immunosuppressive therapeutic response observed in most patients.

DNA extraction and molecular analysis of non-tumoral liver, spleen, and brain from autopsy samples: the effect of formalin fixation and paraffin embedding.

The use of molecular biology in combination with morphological analysis is increasing because of the treatments by target therapies. However, to improve the methods for obtaining DNA for molecular analyses from formalin-fixed, paraffin-embedded (FFPE) tissue is a challenge. The aim of this study was to evaluate the DNA extracted from FFPE tissue blocks (non-tumoral liver, spleen, and brain), obtained from autopsy, 8-24 h post mortem, using three methods of DNA extraction. PCR of the ß-actin (136 pb) and human amelogenin (AMEL 212-218 bp/106-112 bp) genes, as well as short tandem repeat (STR) (100-400 bp fragments), reported in forensic scientific analysis, was performed to evaluate the effectiveness of the methods of DNA extraction. We used 28 archived (1 and 5 years) and 12 recent autopsy cases. The commercial kit showed reproducible and consistent results in the PCR amplification of the ß-actin and AMEL genes and in analysis by STR used in forensic analysis. This is the first report using non-tumoral samples from FFPE autopsy tissues, comparing the three most common methods of DNA extraction and using the STR previously described in forensics. Our study has clarified the challenges for pathologists in applying the molecular biology approach in combination with methods suited for morphology, which must be improved. The data provided here should be used in other molecular studies in FFPE samples.

Patologia do transplante renal: achados morfológicos principais e como laudar as biópsias / Renal transplant pathology: main morphological findings and how to sign out biopsies

O transplante renal alcançou expressivos e crescentes índices de sucesso desde sua implantação, constituindo atualmente uma terapia substitutiva de larga escala. É cada vez mais freqüente o encontro de biópsias de enxerto renal na rotina dos laboratórios de patologia, cujos achados são os mais variados. Este artigo resulta da experiência dos membros do Clube do Rim (da Sociedade Brasileira de Patologia) e apresenta um panorama geral da patologia do transplante renal, enfatizando a atual classificação de Banff, com suas principais categorias e entidades de diagnóstico problemático.

Renal transplant has reached remarkable and growing rates of success since its introduction; nowadays it is a widely used replacement therapy. Renal allograft biopsies are increasingly more frequent in the routine of pathology laboratories, whose histological findings are varied. This paper results from the expertise of the members of the Kidney Club of Sociedade Brasileira de Patologia, and presents a general overview of renal allograft pathology, focusing on the current Banff classification, its main categories and cases of difficult diagnosis.