Pathophysiology and Treatment of Hyperhomocysteinemia in End-Stage Renal Disease Patients.

Abstract

The pathophysiology of hyperhomocysteinemia in end-stage renal disease (ESRD) patients includes impaired remethylation of homocysteine (Hcy) to methionine, inhibition of extrarenal Hcy metabolism by uremic solutes, a block in decarboxylation of cysteinesulfinic acid, impaired [adenosylmethionine]/[adenosylhomocysteine] ratio, and a probable impairment of renal Hcy metabolism and excretion. Treatment of hyperhomocysteinemia in ESRD patients includes administration of folic acid (1 - 15 mg per day). No additional effects have been observed with higher folic acid doses, folinic acid, or 5-methyltetrahydrofolate. Oral supplementation with vitamin B 6 and vitamin B 12 has no effect, but some studies reported a decrease of plasma Hcy with high intravenous vitamin doses. Effective reduction of plasma total Hcy (tHcy) in patients treated with super-flux hemodialyzers suggests the removal of uremic toxins with inhibitory activities against enzymes involved in the extrarenal Hcy metabolism.