Vitamin B_6 Metabolism in Chronic Kidney Disease - Relation to Transsulfuration, Advanced Glycation and Cardiovascular Disease

摘要

Background: Vitamin deficiency is common in chronic kidney disease (CKD). Data on B_6 supply and possible relationships to cardiovascular events (CVE) in CKD are rare. Pyridox-amine exerts inhibitory effects on theformation of advanced glycation endproducts (AGE) Implicated in the pathogenesis of CKD and atherosclerosis. Methods: In 48 CKD patients at stage 2-4,72 hemodialysis patients (HD), 38 renal transplant recipients (RTR) and 141 healthy controls (mean age 58 +- 13, 61 +- 12,50 +- 12 and 54 +- 16 years, respectively), plasma and red blood cell (RBC) concentrations of pyridoxal-5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), pyri-doxamine-5'-phosphate (PMP) and of the AGE pentosidine were measured by high-performance liquid chromatogra-phy, N~epsilon-(carboxymethyl)lysine and imidazolone by an ELISA, and total homocysteine and cystathionine by gas chroma-tography-mass spectrometry. Results: Despite routine low-dose vitamin supplementation in HD, plasma PLP was decreased in HD (79 +- 69 nmol/l) compared with CKD stage 2-4 patients (497 +- 944 nmol/l), RTR (416 +- 604 nmol/l) and controls (159 +- 230 nmol/l; p < 0.001). Plasma PA was significantly increased in HD (11,667 +- 17,871 nmol/l) in comparison with CKD stage 2-4 (435 +- 441 nmol/l), RTR (583 +-668 nmol/l) and controls (46 +- 49 nmol/l; p<0.001).B6forms were significantly affected by renal function (R = 0.792, p < 0.001 for CKD stage 2-4). There was no relation of vitamers with a history of CVE. Relationships between B_6 forms and AGE (RBC-PMP with pentosidine in CKD stage 2-4: R = -0.351, p < 0.05) were found. Conclusion: HD patients showed a deficiency in PLP in plasma but not in RBC. Prospective trials are needed to elucidate the potential role of elevated PA on cardiovascular and renal outcome in CKD. Vitamin B_6 supplementation might be successful in preventing AGE-related pathologies.