Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (1999) 56, 1064–1071; doi:10.1046/j.1523-1755.1999.00624.x
Homocysteine and methionine metabolism in ESRD: A stable isotope study
Coen Van Guldener, Wim Kulik, Ruud Berger, Denise A Dijkstra, Cornelis Jakobs, Dirk-Jan Reijngoud, Ab J M Donker, Coen D A Stehouwer and Kees De Meer
Department of Internal Medicine, Clinical Chemistry, and Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam; University Children's Hospital, Utrecht; and University Hospital Groningen, Groningen, The Netherlands
Correspondence: Coen van Guldener, M.D., Department of Internal Medicine, University Hospital Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: c.vanguldener@azvu.nl
Received 13 November 1998; Revised 9 March 1999; Accepted 31 March 1999.
Abstract
Homocysteine and methionine metabolism in ESRD: A stable isotope study.
Background
Hyperhomocysteinemia has a high prevalence in the end-stage renal disease (ESRD) population, which may contribute to the high cardiovascular risk in these patients. The cause of hyperhomocysteinemia in renal failure is unknown, and therapies have not been able to normalize plasma homocysteine levels. Insight into methionine-homocysteine metabolism in ESRD is therefore necessary.
Methods
Using a primed, continuous infusion of [2H3-methyl-1-13C]methionine, we measured whole body rates of methionine and homocysteine metabolism in the fasting state in four hyperhomocysteinemic hemodialysis patients and six healthy control subjects.
Results
Remethylation of homocysteine was significantly decreased in the hemodialysis patients: 2.6 
0.2 (SEM) vs. 3.8 0.3 
mol 
kg-1 hr-1 in the control subjects (P = 0.03), whereas transsulfuration was not 2.5 0.3 vs. 3.0 0.1 mol kg-1 hr-1 (P = 0.11). The transmethylation rate was proportionally and significantly lower in the ESRD patients as compared with controls: 5.2 0.4 vs. 6.8 0.3 mol kg-1 hr-1 (P = 0.02). Methionine fluxes to and from body protein were similar.
Conclusions
The conversion of homocysteine to methionine is substantially (approximately 30%) decreased in hemodialysis patients, whereas transsulfuration is not. Decreased remethylation may explain hyperhomocysteinemia in ESRD. This stable isotope technique is applicable for developing new and effective homocysteine-lowering treatment regimens in ESRD based on pathophysiological mechanisms.
Keywords:
hemodialysis, breath, cardiovascular risk, hyperhomocysteinemia, renal failure
Abbreviations:
AdoHcy, S-adenosylhomocysteine; ADPKD, autosomal dominant polycystic kidney disease; AdoMet, S-adenosylmethionine; AP, atom percent; APE, atom percent excess; B, methionine from protein breakdown; CGN, chronic glomerulonephritis; ESRD, end-stage renal disease; GCMS, gas chromatography mass spectrometry; HUS, hemolytic uremic syndrome; MPE, mole percent excess; MTHFR, 5, 10-methylenetetrahydrofolate reductase; PCR, polymerase chain reaction; Qc, methionine carboxylflux; Qm, methionine methylflux; R, remethylation; S, methionine to protein synthesis; tHcy, plasma total homocysteine; TM, transmethylation; TS, transsulfuration
