Homocysteine, cystathionine, methylmalonic acid and B-vitamins in patientswith renal disease

Moderate hyperhomocysteinemia is very frequent in renal patients. Aside fro m homocysteine (HCY) itself, the metabolites methylmalonic acid (MMA) and c ystathionine (CYS) supply further information about disturbances in HCY met abolism. In two groups of renal patients, transplant and hemodialysis patie nts, we measured HCY, MMA and CYS and evaluated their diagnostic value for impaired HCY metabolism due to vitamin deficiency and renal insufficiency. We investigated serum samples from 63 transplant patients and 38 patients u ndergoing hemodialysis. HCY, MMA and CYS were assayed by gas chromatography -mass spectrometry, vitamin B-6 by HPLC, B-12 and folate by chemiluminescen ce immunoassay. The determination of HCY, MMA, and CYS in renal patients provides specific information about intracellular disturbances of HCY metabolism. The frequen cy of increased metabolite levels in renal patients was much higher than th e frequency of lowered vitamin concentrations in serum. Furthermore, the me tabolite levels in transplant patients were only moderately increased, wher eas they were strongly increased in patients on hemodialysis (HCY 19.2 vs. 28.8 mu mol/l, MMA 292 vs. 1025 nmol/l, CYS 733 vs. 2711 nmol/l). Our findi ngs may support the use of MMA determination in the diagnosis of vitamin B- 12 deficiency in renal patients. Compared to vitamin B-12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Regression analysis revealed that the moderate elevation of HCY and CYS in transplant patients is mainly a consequence of impaired remethylation of HC Y to methionine with activated transsulfuration, whereas the mildly elevate d MMA level is attributable to renal dysfunction. In patients on hemodialys is, all three metabolites were markedly elevated, indicating a strongly dis turbed HCY metabolism. Based on a backward regression, we discovered that t he HCY metabolism was strongly disturbed by renal insufficiency and vitamin deficiency. The markedly elevated HCY level was mainly attributable to fun ctional vitamin B-12 deficiency indicated by high MMA, and the strong CYS e levation was due to renal dysfunction and inhibition of this pathway by low levels of vitamin B-6. In conclusion, besides HCY, the determination of MMA and CYS levels support s an early diagnosis of B-vitamin deficiency in renal patients. MMA is a mo re sensitive indicator of intracellular vitamin B-12 deficiency than vitami n B-12 in serum.