LONG-TERM FOLIC-ACID (BUT NOT PYRIDOXINE) SUPPLEMENTATION LOWERS ELEVATED PLASMA HOMOCYSTEINE LEVEL IN CHRONIC-RENAL-FAILURE

Moderate hyperhomocysteinemia, a risk factor for premature atheroscler osis, is present in chronic uremic patients. We prospectively evaluate d the effects of sequential supplementation with pyridoxine (70 mg/day ) and folic acid (10 mg/day) for two 3-month periods in 37 nondialyzed patients (29 males) with creatinine clearance (C-Cr) ranging from 10 to 80 ml/min, whose plasma vitamin B-12 and folate level was in the no rmal range. Mean (+/- SD) baseline plasma total homocysteine (Hey) was 14.9 +/- 5.2, 16.5 +/- 5.1 and 26.1 +/- 12.1 mu mol/l (upper limit in 45 healthy controls 14.1 mu mol/l) in patients with C,, 40-80, 20-40 and < 20 ml/min, respectively. Following pyridoxine Hey did not signif icantly decrease whereas following folic acid Hey decreased significan tly to 9.9 +/- 2.9 (-33% vs. baseline), 10.3 +/- 3.4 (-37%) and 15.4 /- 5.5 (-40%), respectively (Student's paired t test, p < 0.001) in th e 3 groups. We conclude that folate (but not pyridoxine) pharmacologic supplementation is effective in lowering elevated plasma Hey in chron ic renal failure patients, thus suggesting that enhancing the Hey reme thylation pathway may overcome hyperhomocysteinemia in such patients. In view of the potential atherogenic effects of hyperhomocysteinemia, long-term folate supplementation should be considered in uremic patien ts.