Early Diabetes Aggravates Renal Ischemia/reperfusion-induced Acute Kidney Injury 

Abstract

Acute kidney injury (AKI) due to ischemia and reperfusion (IR) can be associated with the progression of chronic kidney injury. In addition, studies suggest that chronic diabetes is an independent risk factor for AKI; however, the impact of early diabetes on the severity of AKI remains unknown. We investigated the effects of early diabetes on the pathophysiology of renal IR-induced AKI. C57BL/6J mice were randomly assigned into the following groups: 1) sham-operated; 2) renal IR; 3) streptozotocin (STZ - 55 mg/kg/day) and sham-operated; and 4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 minutes followed by reperfusion for 48 hours, and the mice were euthanized by exsanguination. Renal function was assessed by analyzing the plasma creatinine and urea concentrations with biochemical methods. Proteinuria was evaluated using a commercial kit. Kidney tissue was used to evaluate the morphology, gene expression by qPCR, and protein expression by Western blotting. Compared to the sham operated, renal IR resulted in increased plasma creatinine and urea levels, decreased nephrin mRNA expression, increased tubular cast formation, and Kim-1, Ki-67, pro-inflammatory and pro-fibrotic factor mRNA expression. Compared with the sham treatment, STZ treatment resulted in hyperglycemia, but did not induce changes in kidney function or pro-inflammatory or pro-fibrotic factors. However, STZ treatment aggravated renal IR-induced AKI by exacerbating glomerular and tubular injury, inflammation, and the profibrotic response. Early diabetes constitutes a relevant risk factor for renal IR-induced AKI.