Sodium Depletion Enhances the Antiproteinuric Effect of ACE Inhibition in Established Experimental Nephrosis

R.T. Gansevoort, Department of Nephrology, State University Hospital Groningen, The Netherlands Dear Sir, The beneficial effect of angiotensin-I-converting-enzyme inhibition (ACEi) to prevent both a rise in proteinuria as well as progression of renal function loss has been documented in different models of experimental nephrosis [1]. Extrapolation to the human situation however seems rather hazardous, since the majority of these animal studies started ACEi before or immediately after disease induction, whereas treatment in patients is only started at the time that renal disease is fully established. This difference in disease state when starting ACEi may have consequences for the interpretation of data; the level of proteinuria in the animal studies may be an indication of the amount of structural damage to glomeruli, whereas the antiproteinuric effect of ACEi in the human situation, according for instance to its reversibility, is probably due to a functional alteration. Only a few animal studies have, in analogy to the human situation, investigated the effect of ACEi in an established disease state. Some investigators found no effect of ACEi on proteinuria [2-4], while others found a significant decrease [5-7]. In man sodium depletion is necessary to obtain an optimal antiproteinuric effect of ACEi [8]. We hypothesized that differences in sodium intake and volume status between the above-mentioned animal studies could account for the conflicting results. We therefore studied the effect of differences in sodium intake on proteinuria and on the antiproteinuric effect of ACEi in an experimental model of established adriamy-cin nephrosis. Ten male Wistar rats, age 12 weeks, weighing 270 ± 12 g, were injected with adriamycin in a dose of 3 mg/kg i. v. to induce nephrosis. The study consisted of four periods during which 24hour protein was measured twice weekly and blood pressure once weekly. Every period lasted until a stabilization of proteinuria and blood pressure was achieved. Statistical analysis was performed by non-parametric analysis of variance (Kruskall-Wallis) using the last, stable, values of each period. Significance was assumed at p < 0.05. During the first period all rats were fed a low-salt diet, containing 0.05% NaCl. Six weeks were allowed for proteinuria to develop and stabilize. In period 2, lasting 4 weeks, rats were matched for blood pressure and proteinuria and divided into two groups in order to study the effect of different sodium intake on these parameters. One group (n = 5) continued the low-salt diet, while the other group (n = 5) received