Early type 1 diabetes aggravates renal ischemia/reperfusion-induced acute kidney injury

The present study aimed to investigate the interaction between early diabetes and renal IR-induced AKI and to clarify the mechanisms involved. C57BL/6J mice were assigned to the following groups: (1) sham-operated; (2) renal IR; (3) streptozotocin (STZ-55 mg/kg/day) and sham operation; and (4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 min followed by reperfusion for 48 h, at which time the animals were euthanized. Renal function was assessed by plasma creatinine and urea levels, as well urinary protein contents. Kidney morphology and gene and protein expression were also evaluated. Compared to the sham group, renal IR increased plasma creatinine, urea and albuminuria levels and decreased Nphs1 mRNA expression and nephrin and WT1 protein staining. Tubular injury was observed with increased Havcr1 and Mki67 mRNA expression accompanied by reduced megalin staining. Renal IR also resulted in increased SQSTM1 protein expression and increased proinflammatory and profibrotic factors mRNA expression. Although STZ treatment resulted in hyperglycemia, it did not induce significant changes in renal function. On the other hand, STZ treatment aggravated renal IR-induced AKI by exacerbating renal dysfunction, glomerular and tubular injury, inflammation, and profibrotic responses. Thus, early diabetes constitutes a relevant risk factor for renal IR-induced AKI.

Automated summary

Compared to the sham group, renal ischemia-reperfusion significantly increased plasma creatinine, urea, and albuminuria levels, while decreasing Nphs1 mRNA expression and nephrin and WT1 protein staining. Tubular injury was also observed with increased Havcr1 and Mki67 mRNA expression and reduced megalin staining. This study suggests that early diabetes could exacerbate renal ischemia-reperfusion-induced acute kidney injury by enhancing renal dysfunction, inflammation, and profibrotic responses.