Pharmacological blockade of the renin-angiotensin-system for the prevention of postischemic acute renal failure

Purpose: In urology postischemic acute renal failure is of clinical importance in the field of organ preserving, reconstructive kidney surgery. Inhibition of the renin-angiotensin system significantly improves renal blood flow and decreases renal vascular resistance. This study investigates whether preischemic treatment with modern inhibitors of the renin-angiotensin system can influence the development of renal failure. Material and Methods: After preischemic application of either the angiotensin-converting enzyme inhibitor enalaprilat (2 mg/kg) or the angiotensin Ii-receptor antagonist valsartan (1 mg/kg) postischemic renal function was measured in conscious rats by means of clearance- and Doppler-flow-studies. For this rats underwent 60 minutes of unilateral warm renal ischemia and nephrectomy of the contralateral intact kidney. Renal function measurements were performed in the initial phase 2 hours and in the maintenance phase 48 hours after ischemia. Results: 48 hours after ischemia no mortality was found in the preteated animals. To a similar extent, enalaprilat and valsartan showed a residual renal blood flow and residual glomerular filtration rate of 33% and 25%, respectively, compared to lower than 10% under control conditions. Renal vascular resistance after pretreatment increased to 3.5 to 5fold of normal values compared to an 80fold increase under control conditions. After enalaprilat and valsartan serum creatinine-levels were only half of the values in untreated animals. Conclusions: Preischemic inhibition of the renin-angiotensin system shows renoprotectice effects with regard to renal function parameters 48 hours after ischemia. This is a new information especially for the angiotensin II receptor antagonist valsartan. However the results also indicate that renal failure can only be ameliorated but not prohibited because of multifactorial pathogenesis of the disease. Nevertheless in our own experience under clinical conditions the i.v. application of enalaprilat before surgically induced ischemia helps significantly to improve the postischemic reflow and development of diuresis in patients.