Homocysteine in the plasma of renal transplant recipients: effects of cofactors for methionine metabolism.

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine-homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 ageand sex-matched normal subjects with particular emphasis on sulphur-containing amino acids. 2. Plasma cysteine-homocysteine mixed disulphide was increased in the patients (mean 6.0 k SD 3.2 pmolll; normal 3.1 & 0.9 pmol/l, P < 0.001) and homocystine was detectable in low concentration ((1.0 pmol/l) in 24; the elevation in cysteine-homocysteine was related to serum creatinine ( r = 0.60, P < 0.002). Cystine was also increased (91.6 Ifr 29.3 pmolll; normal subjects 64.0 f 16.7 pmol/l, P < 0-OOI), but methionine concentrations were normal. 3. When pyridoxine, folic acid and vitamin B,,, cofactors for homocysteine metabolism, were administered sequentially to 1 1 arbitrarily selected transplant recipients cysteine-homocysteine decreased from 7.3 +_ 2.1 to 4.3 f 0.8 pmol/l ( P < 0.001) and homocystine became undetectable. The response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B,, concentrations. 4. In eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine-homocysteine from 9.0 f 3.1 to 5.4 f 1.6 pmol/l over a 4 week