A Micropuncture Study of a Dietary Induced, Hyperuricemic Model of Acute Renal Failure in the Rat

Abstract

Acute renal failure as the result of an increased plasma urate concentration is a well-documented phenomenon in clinical settings, particularly following chemotherapy of leukemias (1). Stavric et al.(2) were the first to develop a suitable model to study this form of nephropathy in the rat. Their method utilized a dietary supplement of uric acid given simultaneously with oxonic acid, to block the rat's endogenous hepatic uricase. This resulted in elevated plasma urate concentrations. Previous micropuncture studies (3 -5) have provided experimental evidence for the prese n c e of t u b u l a r o b s t r u c t i o n i n t h e pathogenesis of this model of acute renal failure. However, neither paper included an assessment of the contribution of changes in glomerular dynamics on impaired renal function. We have measured whole kidney and single nephron function and have attempted to assess the contributions of tubular obstruction and of changes in glomerular dynamics to the pathogenesis of this model. Materials and methods. Male, albino Sprague-Dawley rats (Charles River Laboratories) were used throughout the study (N = 40, mean body weight = 261 k 55 g). Animals were anesthetized prior to surgery with an intraperitoneal dose of Nembutal (sodium pentobarbital, Abbott, 60 mg/kg body wt). Maintenance infusions of 0.85% sodium chloride containing inulin for estimation of inulin clearance and para-aminohippuric acid (PAH) to estimate renal plasma flow were infused at 2.34 mVhr 187 0037-9727/80/