To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 +/- 0.4 (SE) mg x dl(-1); range 3.3-9.1). Patients' age and body mass index were 53 +/- 4 years (range 26-73) and 24.7 +/- 0.6 kg/m2 (range 20.3-28.7), respectively. Nutritional status (plasma albumin 3.6 +/- 0.4 g x dl[-1]) and acid-base equilibrium (arterial pH 7.38 +/- 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-(13)C]leucine was continuously infused and plasma [1-(13)C]alpha-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Rawas 2.03 +/- 0.13 micromol x kg(-1) x min(-1) (range 1.29-3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.