Leucine turnover in patients with nephrotic syndrome: evidence suggesting body protein conservation

Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.