Tubular Function in Glycerol Induced Acute Renal Failure in Rats: Effect of Saline Loading and Prior Acute Renal Failure

Abstract

1. Chronic saline loading and prior induction of acute renal failure are manoeuvres which have been reported to protect against the development of acute renal failure. The underlying mechanisms are unclear. The purpose of the present study was to examine the effect of these protective manoeuvres on glomerular filtration rate (GFR) and proximal and distal tubular function in the glycerol-induced model of acute renal failure. 2. Acute renal failure was induced (50% glycerol, 10 ml/kg body wt. intramuscularly) in three groups of rats: group 1, water drinking; group 2, saline loaded (1% NaCl as drinking fluid for 5 weeks); group 3, rechallenged 7–15 days after a first dose of glycerol, when blood urea nitrogen levels had returned to normal. Control animals in group 3 received only the first glycerol injection, then, like the controls in groups 1 and 2, they were given 0.9% NaCl solution (10 ml/kg body wt. intramuscularly). All animals were then studied 24 h after glycerol or saline injection. 3. Glycerol caused a significant fall in GFR in all three groups (78% group 1; 64% group 2; 59% group 3); blood urea nitrogen levels rose significantly. Saline-loaded animals with acute renal failure (group 2) exhibited glycosuria with normal blood-sugar levels and a striking depression in maximal tubular glucose reabsorption. The capacity to reabsorb HCO−3 was depressed both before and during HCO−3 loading. Distal acidification as assessed by the urine to blood gradient of Pco2 (U—B Pco2) was normal during HCO−3 loading (urine pH 7.8). The presence of hyperchloraemic metabolic acidosis demonstrated that these animals developed proximal renal tubular acidosis. Glycerol-reinjected rats with acute renal failure (group 3) reabsorbed glucose and HCO−3 normally and exhibited normal distal tubule acidification. 4. We conclude from these data that a prior episode of acute renal failure protects proximal tubules against a second glycerol challenge, whereas chronic saline loading is without this protective effect. Both the underlying mechanism for this tubular cell resistance (against a second glycerol challenge) and the role of proximal tubular function in the pathogenesis of acute renal failure remain unclear.