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 importa nce in the field of organ preserving, reconstructive kidney surgery. Inhibi tion of the renin-angiotensin system significantly improves renal blood flo w and decreases renal vascular resistance. This study investigates whether preischemic treatment with modern inhibitors of the renin-angiotensin syste m can influence the development of renal failure. Material and Methods: After preischemic application of either the angiotens in-converting enzyme inhibitor enalaprilat (2 mg/kg) or the angiotensin Ii- receptor antagonist valsartan (1 mg/kg) postischemic renal function was mea sured in conscious rats by means of clearance- and Doppler-flow-studies. Fo r this rats underwent 60 minutes of unilateral warm renal ischemia and neph rectomy of the contralateral intact kidney. Renal function measurements wer e performed in the initial phase 2 hours and in the maintenance phase 48 ho urs after ischemia. Results: 48 hours after ischemia no mortality was found in the preteated an imals. To a similar extent, enalaprilat and valsartan showed a residual ren al blood flow and residual glomerular filtration rate of 33% and 25%, respe ctively, compared to lower than 10% under control conditions. Renal vascula r 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 untre ated animals. Conclusions: Preischemic inhibition of the renin-angiotensin system shows r enoprotectice effects with regard to renal function parameters 48 hours aft er ischemia. This is a new information especially for the angiotensin II re ceptor antagonist valsartan. However the results also indicate that renal f ailure can only be ameliorated but not prohibited because of multifactorial pathogenesis of the disease. Nevertheless in our own experience under clin ical conditions the i.v. application of enalaprilat before surgically induc ed ischemia helps significantly to improve the postischemic reflow and deve lopment of diuresis in patients.