Background: Vitamin deficiency is common in chronic kidney disease (CKD). Data on B6 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, NΕ-(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). B6 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 B6 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 B6 supplementation might be successful in preventing AGE-related pathologies.

Keywords:
Advanced glycation end products, Cardiovascular disease, Chronic kidney disease, Pyridoxal phosphate, Transsulfuration, Vitamin B6
1.
Coburn SP, Reynolds RD, Mahuren JD, Schaltenbrand WE, Wang Y, Ericson KL, et al: Elevated plasma 4-pyridoxic acid in renal insufficiency. Am J Clin Nutr 2002;75:57–64.
2.
Bates CJ: Vitamin analysis. Ann Clin Biochem 1997;34:599–626.
3.
Lumeng l, Lui A, Li TK: Plasma content of B6 vitamers and its relationship to hepatic vitamin B6 metabolism. J Clin Invest 1980;66:688–695.
4.
Anderson BB, Newmark PA, Rawlins M, Green R: Plasma binding of vitamin B6 compounds. Nature 1974;250:502–504.
5.
Finkelstein JD: Methionine metabolism in mammals. J Nutr Biochem 1990;1:228–237.
6.
Midttun O, Hustad S, Schneede J, Vollset SE, Ueland PM: Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 2007;86:131–138.
7.
Lindner A, Bankson DD, Stehman-Breen C, Mahuren JD, Coburn SP: Vitamin B6 metabolism and homocysteine in end-stage renal disease and chronic renal insufficiency. Am J Kidney Dis 2002;39:134–145.
8.
Mydlik M, Derzsiova K, Zemberova E: Metabolism of vitamin B6 and its requirement in chronic renal failure. Kidney Int 1997;62(suppl):S56–S59.
9.
Goldin A, Beckman JA, Schmidt AM, Creager MA: Advanced glycation end products sparking the development of diabetic vascular injury. Circulation 2006;114:597–605.
10.
Nakamura S, Li H, Adijang A, Pischetsrieder M, Niwa T: Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol Dial Transplant 2007;22:2165–2174.
11.
Voziyan PA, Metz TO, Baynes JW, Hudson BG: A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation. J Biol Chem 2002;277:3397–3403.
12.
Busch M, Franke S, Müller A, Wolf M, Gerth J, Ott U, Niwa T, Stein G: Potential cardiovascular risk factors in chronic kidney disease: AGEs, total homocysteine and metabolites, and the C-reactive protein. Kidney Int 2004;66:338–347.
13.
Bitsch R, Möller J: Analysis of B6 vitamers in foods using a high-performance liquid chromatographic method. J Chromatogr 1989;463:207–211.
14.
Klemm A, Franke C, Busch M, Müller A, Franke S, Lang D, Passlick-Deetjen J, Stein G: Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites. Clin Nephrol 2004;61:191–197.
15.
Dietary Reference Intakes: Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, National Academic Press, 1998.
16.
Bitsch R: Vitamin B6. Int J Vitam Nutr Res 1993;63:278–282.
17.
Bates CJ, Pentieva KD, Prentice A, Mansoor MA, Finch S: Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over. Br J Nutr 1999;81:191–201.
18.
Ink SL, Mehansho H, Henderson LM: The binding of pyridoxal to hemoglobin. J Biol Chem 1982;257:4753–4757.
19.
Gaut ZN, Solomon HM: Phosphorylation of pyridoxine by human blood platelets – effects of structure analogs and metabolic inhibitors. Biochem Pharmacol 1972;21:2395–2400.
20.
Lin PT, Cheng CH, Liaw YP, Lee BJ, Lee TW, Huang YC: Low pyridoxal 5′-phosphate is associated with increased risk of coronary artery disease. Nutrition 2006;22:1146–1151.
21.
Lin PT, Cheng CH, Wei JC, Huang YC: Low plasma pyridoxal 5′-phosphate concentration and MTHFR 677C→T genotypes are associated with increased risk of hypertension. Int J Vitam Nutr Res 2008;78:33–40.
22.
Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J: Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995;346:85–89.
23.
Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willet WC: Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 1996;143:845–859.
24.
Friedmann AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH: The kidney and homocysteine metabolism. J Am Soc Nephrol 2001;12:2181–2189.
25.
Stabler SP, Lindenbaum J, Savage DG, Allen RH: Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood 1993;81:3404–3413.
26.
Davis SR, Quinlivan EP, Stacpoole PW, Gregory JF III: Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women. J Nutr 2006;136:373–378.
27.
House JD, Brosnan ME, Brosnan JT: Characterization of homocysteine metabolism in the rat kidney. Biochem J 1997;328:287–292.
28.
van Guldener C, Kulik W, Berger R, Dijkstra DA, Jakobs C, Reijngoud DJ, Donker AJM, Stehouwer CDA, de Meer K: Homocysteine and methionine metabolism in ESRD: a stable isotope study. Kidney Int 1999;56:1064–1071.
29.
Obeid R, Kuhlmann MK, Köhler H, Herrmann W: Response of homocysteine, cystathionine, and methylmalonic acid to vitamin treatment in dialysis patients. Clin Chem 2005;51:196–201.
30.
Alderson NL, Chachich ME, Youssef NN, Beattie RJ, Nachtigal M, Thorpe SR, Baynes JW: The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats. Kidney Int 2003;63:2123–2133.
31.
Culbertson SM, Vassilenko EI, Morrison LD, Ingold KU: Paradoxical impact of antioxidants on post-Amadori glycoxidation. J Biol Chem 2003;278:38384–38394.
32.
Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB: Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 2007;27:605–614.
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2009
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