REDUCTION OF REMNANT NEPHRON HYPERMETABOLISM BY PROTEIN RESTRICTION

To study the metabolic mechanisms involved in the protective effect of dietary protein restriction on the progression of chronic renal failure, experiments were performed in Sprague-Dawley rats subjected to five-sixths nephrectomy and pair-fed on isocaloric low (4%) protein (LP) or high (50%) protein (HP) diets. Protein restriction reduced the severity of uremia, with lower blood urea nitrogen (BUN) concentrations (8.9 ± 1.1 v 30.0 ± 2.9 mmol/L [25 ± 3 v 84 ± 8 mg/ dL] both n = 12, P < 0.01), and resulted in lower mortality at 2 weeks (0% v 33%, P < 0.05), 4 weeks (16% v 58%, P < 0.05), and 10 weeks (16 v 83%, P < 0.01). Isolated perfusion of the remnant kidney at 3 weeks demonstrated reduced O2 consumption (Qo2) (0.77 ± 0.2 v 2.56 + 0.5 µmol/min/g, both n = 7, P < 0.05) in the absence of significant differences in inulin clearance (239 ± 53 v 341 ± 39 µL/min/g, NS) and net sodium reabsorption (34 ± 8 v 49 ± 6 µmol/min/g, NS) in rats fed the LP diet. A lower renal Qo2 in protein-restricted animals was also demonstrated in vivo (4.1 ± 0.9 v 13.8 ± 2.7 µmol/min/g, P < 0.01). In vivo P-31 nuclear magnetic resonance (NIVIR) studies of remnant kidneys did not demonstrate any difference in the steady-state tissue concentrations of adenosine triphosphate (ATP) or inorganic phosphate between rats fed LP and HP diets. Dietary protein restriction decreases the severity of uremia and diminishes renal 002 in the remnant kidney model. Thus, attenuation of hypermetabolism may mediate the protective effect of dietary protein restriction, at least in part, in this model of chronic renal failure. © 1991, National Kidney Foundation, Inc.. All rights reserved.