Patients on dialysis have a substantially higher mortality rate compared with the general population. Dialysis is usually associated with an increased plasma level of homocysteine (Hcy). Hcy is viewed as a nontraditional marker of the prognosis of cardiovascular disease (CVD) in the general population and in patients with chronic kidney disease. The effects of Hcy-lowering therapy in patients with end-stage renal disease (ESRD) remain controversial. We searched multiple databases including PubMed, MEDLINE, and OVID, and conducted a systematic review of the literature. Possible therapeutic measures were also surveyed. Our review shows that effective normalization of plasma Hcy level may decrease CVD-related morbidity and mortality in nondiabetic ESRD patients. Hyperglycemia in association with diabetes mellitus makes ESRD patients resistant to Hcy-lowering therapy. Folic acid fortification may attenuate the beneficial effects of Hcy-lowering therapy. Supraphysiological doses of folic acid and vitamin B supplementation might be needed in ESRD patients with diabetes or high Hcy levels. The response to Hcy-lowering therapy may be influenced by differences within and between populations in sex, genotype, nutrition, and mandatory fortification. Treatment resistance found mainly in diabetic ESRD patients but not in nondiabetic ESRD patients that may need other therapeutic approaches.
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