Enhanced renal ischemia-reperfusion injury in aging and diabetes

Abstract

The incidence and severity of acute kidney injury is increased in patients with diabetes and with aging. However, the mechanisms involved have not been clearly established. The present study examined the effects of aging and diabetes on the severity of renal ischemia-reperfusion (IR) injury in Sprague-Dawley (SD) and type 2 diabetic (T2DN) rats. T2DN rats develop diabetes at 3 mo of age and progressive proteinuria and diabetic nephropathy as they age from 6 to 18 mo. Plasma creatinine levels after bilateral IR were significantly higher (3.4 ± 0.1 mg/dl) in 18-mo-old elderly T2DN rats than in middle-aged (12 mo) T2DN rats with less severe diabetic nephropathy or young (3 mo) and elderly (18 mo) control SD rats (1.5 ± 0.2, 1.8 ± 0.1, and 1.7 ± 0.1 mg/dl, respectively). Elderly T2DN rats exhibited a greater fall in medullary blood flow 2 h following renal IR and a more severe and prolonged decline in glomerular filtration rate than middle-aged T2DN and young or elderly SD rats. The basal expression of the adhesion molecules ICAM-1 and E-selectin and the number of infiltrating immune cells was higher in the kidney of elderly T2DN than age-matched SD rats or young and middle-aged T2DN rats before renal IR. These results indicate that elderly T2DN rats with diabetic nephropathy are more susceptible to renal IR injury than diabetic animals with mild injury or age-matched control animals. This is associated with increased expression of ICAM-1, E-selectin and immune cell infiltration, renal medullary vasocongestion, and more prolonged renal medullary ischemia.