Aspects of folate metabolism in renal failure

Plasma and urine folate fractions were evaluated after ingestion of radioactive N5-methyl-tetrahydrofolic acid by a normal control (subject I), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radiofolate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject I to be compatible with N5-methyl-tetrahydrofolic acid (peak I). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10-formyl-tetrahydrofolate. Peak I was minimally present in subject 3. This limited study suggest a defect of methyl-tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se. In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks I and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis-resistant (bound plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate 'binder' detected with haemoglobin-coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.