To investigate the short-term renal effects of protein restriction and unchanged salt intake in chronic renal failure (CRF), patients with moderate CRF (creatinine clearance 41 +/- 5 ml/min) and healthy controls (CON) ate a normal protein diet (NPD) for four weeks, and thereafter a low protein diet (LPD, 0.4 g/kg body wt/day) for three weeks. The two diets were isocaloric and with a salt intake of 10 to 13 g/day. No differences in body weight, serum proteins and plasma sodium were recorded throughout the study. During LPD, inulin and PAH clearances in CON demonstrated a progressive 25% decline of basal GFR and RPF; on the contrary, in CRF, basal renal function did not change in presence of a significant reduction of proteinuria. In CON patients after protein restriction, fractional free-water generation (CH2O/CIn) and fractional urinary excretion of sodium (FENa) measured under maximal water diuresis increased progressively, both being doubled at the end of LPD, while in CRF, CH2O/CIn did not change and FENa values remained unmodified and much higher (above 4%) than in CON after both diets. The renal response to an acute oral protein load (OPL) and i.v. low-doses of dopamine (D) was measured at the end of each period; in the two groups, GFR and RPF significantly increased following OPL + D after both diets. In CRF, however, the vasodilatory response was blunted overall being reduced after both LPD and NPD, and, unlike CON, it did not increase after LPD.(ABSTRACT TRUNCATED AT 250 WORDS)