Vitamin B6 metabolism in chronic kidney disease--relation to transsulfuration, advanced glycation and cardiovascular disease.
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. Pyridoxamine exerts inhibitory effects on the formation 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), pyridoxamine-5'-phosphate (PMP) and of the AGE pentosidine were measured by high-performance liquid chromatography, N(epsilon)-(carboxymethyl)lysine and imidazolone by an ELISA, and total homocysteine and cystathionine by gas chromatography-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). B(6) forms 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.


CONCLUSIONS
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.
Busch
Martin
M
Department of Internal Medicine III, University of Jena, Jena, Germany. martin.busch@med.uni-jena.de
Göbert
Andrea
A
Franke
Sybille
S
Ott
Undine
U
Gerth
Jens
J
Müller
Andreas
A
Stein
Günter
G
Bitsch
Roland
R
Wolf
Gunter
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011730:Pyridoxal / Q000097:blood; D011732:Pyridoxal Phosphate / Q000097:blood; D011733:Pyridoxamine / Q000097:blood; D011735:Pyridoxic Acid / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000378:metabolism*; D025101:Vitamin B 6 / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D011730:Pyridoxal; D011735:Pyridoxic Acid; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D025101:Vitamin B 6