ABSTRACT
BACKGROUND: Hyperhomocysteinemia is present in the majority of chronic hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6 cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we have demonstrated the tHcy-lowering effect of creatine supplementation in an animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study investigates the effects of creatine supplementation on tHcy in a vitamin-repleted chronic hemodialysis population. METHODS: Forty-five hemodialysis patients receiving folic acid and vitamin B6 and B12 were included. Patients were treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid, vitamin B12, and routine biochemistry were determined, as well as the prognostic inflammatory and nutritional index. RESULTS: All patients had elevated tHcy concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in increased plasma and red blood cell creatine levels, documenting uptake of creatine. Creatine did not affect tHcy concentrations. There was no relationship between plasma creatine concentrations and tHcy concentrations. No changes in body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12 were observed during the study. CONCLUSION: Creatine supplementation at a rate of 2 g/day does not further decrease tHcy concentrations in chronic dialysis patients already treated with high dose folic acid, vitamin B6, and B12 supplementation.
Subject(s)
Creatine/administration & dosage , Homocysteine/blood , Hyperhomocysteinemia/drug therapy , Kidney Failure, Chronic/complications , Renal Dialysis , Aged , Aged, 80 and over , Creatine/blood , Cross-Over Studies , Female , Folic Acid/administration & dosage , Folic Acid/blood , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/etiology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Middle Aged , Nutrition Assessment , Vitamin B 12/administration & dosage , Vitamin B 12/blood , Vitamin B 6/administration & dosage , Vitamin B 6/bloodABSTRACT
BACKGROUND: Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required. Modifications of the dialysis regimen may result in a better removal of Hcy. We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients. METHODS: Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux, a high-flux and a super-flux membrane, in random order. Pre-dialysis tHcy was determined at baseline and every 4 weeks. In 18 patients, plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured. RESULTS: Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis (-14.6 +/- 2.8%), whereas it remained stable during high-flux (+0.5 +/- 2.4%) and low-flux dialysis (+1.7 +/- 3.2%). The homocysteine reduction ratio was not different for the three membranes: 0.39 +/- 0.03 for the super-flux, 0.47 +/- 0.02 for the high-flux and 0.39 +/- 0.02 for the low-flux dialyser. The amount of Hcy recovered in the dialysate during a single dialysis session was also similar: 117.5 +/- 3.6 micro mol during super-flux, 95.3 +/- 11.5 micro mol during high-flux and 116.5 +/- 11.6 micro mol during low-flux dialysis. CONCLUSION: Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients. Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes, rather than better dialytic clearance of Hcy itself, may explain the beneficial effect of the super-flux membrane.
