Hyperglycemia exacerbates and insulin fails to protect in acute renal ischemia in the rat

Abstract

Hyperglycemia worsens ischemic injury in several ischemic models. To determine whether renal lactate accumulation was associated with hyperglycemia-exacerbated postischemic renal dysfunction and mortality, halothane-anesthetized rats underwent right nephrectomy and 45 min of left renal artery and vein occlusion. Prior to ischemia, rats received saline (n = 22), glucose (2 g/kg, n = 22), or insulin (4 U/kg, n = 18). Sham-operated glucose-treated rats (2 g/kg, n = 4) underwent right nephrectomy and no vascular occlusion. As anticipated, glucose pretreatment elevated plasma glucose, while insulin pretreatment lowered plasma glucose; both were significantly different from values in saline controls. Creatinine was unchanged in sham-operated rats but was significantly higher in glucose-treated rats at 24 and 48 hr postischemia compared to saline controls. No statistical differences in creatinine were found when comparing saline controls to insulin-treated rats. Eighteen percent of glucose-treated rats survived to 72 hr postocclusion, while 45% of insulin-treated rats, 73% of saline control rats, and 100% of sham-operated rats survived this period. In a separate but identical treatment protocol, renal tissue was serially sampled and lactate content was determined in rats pretreated with saline (n = 7), glucose (n = 6) or insulin (n = 6) or sham-operated (n = 2) and receiving identical operation. Tissue lactate concentration did not change during serial sampling in the sham group. During ischemia, lactate was significantly higher in glucose-treated rats and significantly lower in insulin-treated rats as compared to saline controls. The adverse effects of exogenous glucose and attendant hyperglycemia on renal function during normothermic renal ischemia are demonstrated. Increased anaerobic metabolism of glucose with marked lactate accumulation may increase the severity of injury. However, a direct link between tissue lactate and ischemic damage is not fully supported since insulin reduced renal lactate but failed to lessen morbidity and mortality.