It is important to lower homocysteine in dialysis patients.
Homocysteine has been implicated in atherosclerotic and thrombotic vascular disease in the general and in the end-stage renal disease (ESRD) population as well. Although not strong, the risk associated with raised homocysteine (25% risk excess for a 5 mum increase) is quite consistent across studies in the general population. Likewise, individuals harboring a polymorphism leading to higher homocysteine levels coherently display an increased risk for cardiovascular events in comparison with individuals without such a polymorphism. Randomized controlled trials of homocysteine-lowering therapy performed so far failed to prove causality but the size effect of these interventions is still compatible with the hypothesis that reducing the plasma levels of this aminoacid may be beneficial. In ESRD, high homocysteine is a coherent predictor of death and adverse cardiovascular events in patients without malnutrition and inflammation. In the sole randomized placebo-controlled study performed in this population folic acid produced a small beneficial effect which, because of the lack of power, failed to achieve statistical significance. In another randomized study testing the effect of a well established homocysteine-lowering agent, N-acetyl-cysteine, a 40% reduction in cardiovascular events was observed. There is still insufficient knowledge to draw definitive conclusions on the causal implication of homocysteine in the high risk of ESRD. The contention that the homocysteine pathway cannot be used for interventions aimed at curbing cardiovascular risk in this population is, at least by now, unwarranted.
Zoccali
Carmine
C
Nephrology, Hypertension & Renal Transplantation Unit, CNR-IBIM Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, Reggio Calabria, Italy. carmine.zoccali@tin.it
Mallamaci
Francesca
F
Tripepi
Giovanni
G
D000111:Acetylcysteine / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D006435:Renal Dialysis
D006710:Homocysteine; D000111:Acetylcysteine