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Nephrology Dialysis Transplantation, Vol 13, Issue 7 1723-1730, Copyright © 1998 by Oxford University Press


ORIGINAL ARTICLES

The effect of uraemia, acidosis, and dialysis treatment on protein metabolism: a longitudinal leucine kinetic study

V Lim, K Yarasheski and M Flanigan
Departments of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA; Washington University Medical School, St Louis, MO, USA; Corresponding author at: Nephrology Division, Department of Internal Medicine, T310, GH, University of Iowa Hospitals, Iowa City, IA 52242, USA

Background: Uraemia and dialysis are viewed as catabolic processes resulting in malnutrition in chronic renal failure (CRF) patients. To sort out the effects of uraemia, acidosis, and dialysis on protein metabolism, we measured leucine flux in CRF patients before and after initiation of maintenance dialysis. Subjects and methods: Whole-body leucine flux was measured by primed-constant infusion of L[1-13C]leucine in nine CRF patients longitudinally; twice before and once after initiation of maintenance dialysis (D). Before dialysis, one leucine flux was measured when the patients were acidotic (A), and the other, when acidosis was corrected with NaHCO, (NA). Five normal subjects underwent one single leucine flux measurement to serve as control (N). Both patients and normal subjects consumed a constant diet for 6 days and leucine flux was measured on the 7th day 12 h post-absorption. Diet for the CRF patients was identical during the three periods. Plasma L[1-13C]leucine and L[1-13C]KIC were measured by gas chromatography/mass spectrometry and expired 13CO2 by isotope ratio spectrometry. Leucine kinetics were calculated using standard equations. Results: Plasma CO2 levels were 19, 26 and 31 mmol/l in A, NA and D periods respectively. All kinetic results (&mgr;mol/kg/h) are presented as means±SD in the order of A, NA, D, and N, and CRF values that are statistically different from N are identified (*). The amounts of leucine release from endogenous protein breakdown (Ra or Q) were 101±12* 95±9* 113±22 and 117±6. Leucine oxidation (C), quantities of leucine irreversibly oxidized to CO2, were 16.5±5.4, 9.7±3.7*, 12.3±3.0*, and 23.2±3.1. Leucine protein incorporation levels (S) were 85±10, 85±8, 101±19 and 94±6. The S of 101 in CRF patients at period D was statistically higher than those during A and NA periods. Conclusions: These data indicate that when acidosis was corrected, CRF patients adapted to lower protein intake by reducing amino-acid oxidation and protein degradation, and maintained protein synthesis at normal levels. Metabolic acidosis impaired the downregulation of amino-acid oxidation. Maintenance dialysis treatment longitudinally restored protein flux to normal and increased protein synthesis. The general notion that uraemia and dialysis are protein catabolic is not supported by this work. Key words: leucine kinetics; protein turnover; uraemia
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