Two cardiovascular risk factors in one? Homocysteine and its relation to glomerular filtration rate: A meta-analysis of 41 studies with 27,000 participants

Kidney and Blood Pressure Research

Volumn 31, Issue 4, 2008, Pages 259-267

  Kielstein, Jan T ^a,c   Salpeter, Shelley R ^a   Buckley, Nicholas S ^b   Cooke, John P ^a   Fliser, Danilo ^c  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

^c HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

Cockcroft Gault equation; Glomerular filtration rate; Homocysteine; Kidney; Meta analysis; Modification of Diet in Renal Disease formula; Risk factors

Indexed keywords

HOMOCYSTEINE;

AMINO ACID BLOOD LEVEL; ARTICLE; CARDIOVASCULAR RISK; CORRELATION COEFFICIENT; GLOMERULUS FILTRATION RATE; HUMAN; KIDNEY CLEARANCE; KIDNEY FUNCTION; PRIORITY JOURNAL;

CARDIOVASCULAR DISEASES; GLOMERULAR FILTRATION RATE; HOMOCYSTEINE; KIDNEY FUNCTION TESTS; RISK FACTORS;

EID: 48749131987     PISSN: 14204096     EISSN: None     Source Type: Journal    
DOI: 10.1159/000142725     Document Type: Article

References (81)

1. McCully KS: Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56:111-128.
2. Selhub J, Jacques PF, Bostom AG, D'Agostino RB, Wilson PW, Belanger AJ, O'Leary DH, Wolf PA, Schaefer EJ, Rosenberg IH: Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 1995;332:286-291.
3. Schnabel R, Lackner KJ, Rupprecht HJ, Espinola-Klein C, Torzewski M, Lubos E, Bickel C, Cambien F, Tiret L, Munzel T, Blankenberg S: Glutathione peroxidase-1 and homocysteine for cardiovascular risk prediction: results from the AtheroGene study. J Am Coll Cardiol 2005;45:1631-1637.
4. Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K: Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-1588.
5. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr: Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-1577.
6. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M: Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
7. Loscalzo J: Homocysteine trials: clear outcomes for complex reasons. N Engl J Med 2006;354:1629-1632.
8. Brattstrom L, Wilcken DE: Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr 2000;72:315-323.
9. Aksoy N, Aksoy M, Cakmak M, Serdar GH, Davutoglu V, Soydinc S, Meram I: Increased homocysteine in heart failure: a result of renal impairment? Clin Chem Lab Med 2006;44:1324-1329.
10. Arnadottir M, Hultberg B, Nilsson-Ehle P, Thysell H: The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. Scand J Clin Lab Invest 1996;56:41-46.
11. Kielstein JT, Boger RH, Bode-Boger SM, Frolich JC, Haller H, Ritz E, Fliser D: Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 2002;13:170-176.
12. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW: Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154-2169.
13. Zee RY, Mora S, Cheng S, Erlich HA, Lindpaintner K, Rifai N, Buring JE, Ridker PM: Homocysteine, 5,10-methylenetetrahydrofolate reductase 677C>T polymorphism, nutrient intake, and incident cardiovascular disease in 24,968 initially healthy women. Clin Chem 2007;53:845-851.
14. Darius H, Pittrow D, Haberl R, Trampisch HJ, Schuster A, Lange S, Tepohl HG, Allenberg JR, Diehm C: Are elevated homocysteine plasma levels related to peripheral arterial disease? Results from a cross-sectional study of 6,880 primary care patients. Eur J Clin Invest 2003;33:751-757.
15. Francis ME, Eggers PW, Hostetter TH, Briggs JP: Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int 2004;66:303-312.
16. Guallar E, Silbergeld EK, Navas-Acien A, Malhotra S, Astor BC, Sharrett AR, Schwartz BS: Confounding of the relation between homocysteine and peripheral arterial disease by lead, cadmium, and renal function. Am J Epidemiol 2006;163:700-708.
17. DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188.
18. Altman DG, Bland JM: Interaction revisited: the difference between two estimates. BMJ 2003;326:219.
19. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-1057.
20. Homocysteine Studies Collaboration: Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002;288:2015-2022.
21. Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD: Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation 2000;101:1506-1511.
22. Iso H, Moriyama Y, Sato S, Kitamura A, Tanigawa T, Yamagishi K, Imano H, Ohira T, Okamura T, Naito Y, Shimamoto T: Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation 2004;109:2766-2772.
23. Ridker PM, Shih J, Cook TJ, Clearfield M, Downs JR, Pradhan AD, Weis SE, Gotto AM Jr: Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events. Circulation 2002;105:1776-1779.
24. Vollset SE, Refsum H, Tverdal A, Nygard O, Nordrehaug JE, Tell GS, Ueland PM: Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr 2001;74:130-136.
25. Zylberstein DE, Bengtsson C, Bjorkelund C, Landaas S, Sundh V, Thelle D, Lissner L: Serum homocysteine in relation to mortality and morbidity from coronary heart disease: a 24-year follow-up of the population study of women in Gothenburg. Circulation 2004;109:601-606.
26. Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE: Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 1998;98:204-210.
27. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, Rosenberg IH: Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med 1999;131:321-330.
28. Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA: Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004;351:1285-1295.
29. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-1305.
30. Menon V, Sarnak MJ, Greene T, Wang X, Pereira AA, Beck GJ, Kusek JW, Selhub J, Collins AJ, Levey AS, Shlipak MG: Relationship between homocysteine and mortality in chronic kidney disease. Circulation 2006;113:1572-1577.
31. Wilcken DE, Gupta VJ: Sulphr containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixed disulphide. Eur J Clin Invest 1979;9:301-307.
32. Canepa A, Carrea A, Caridi G, Dertenois L, Minniti G, Cerone R, Canini S, Calevo MG, Perfumo F: Homocysteine, folate, vitamin B 12 levels, and C677T MTHFR mutation in children with renal failure. Pediatr Nephrol 2003;18:225-229.
33. Diakoumopoulou E, Tentolouris N, Kirlaki E, Perrea D, Kitsou E, Psallas M, Doulgerakis D, Katsilambros N: Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors. Nutr Metab Cardiovasc Dis 2005;15:109-117.
34. Flicker LA, Vasikaran SD, Thomas J, Acres JG, Norman PE, Jamrozik K, Lautenschlager NT, Leedman PJ, Almeida OP: Homocysteine and vitamin status in older people in Perth. Med J Aust 2004;180:539-540.
35. Jabs K, Koury MJ, Dupont WD, Wagner C: Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children. Metabolism 2006;55:252-257.
36. Loffredo L, Violi F, Fimognari FL, Cangemi R, Sbrighi PS, Sampietro F, Mazzola G, Di Lecce VN, D'Angelo A: The association between hyperhomocysteinemia and ischemic stroke in patients with non-valvular atrial fibrillation. Haematologica 2005;90:1205-1211.
37. Schafer SA, Mussig K, Stefan N, Haring HU, Fritsche A, Balletshofer BM: Plasma homocysteine concentrations in young individuals at increased risk of type 2 diabetes are associated with subtle differences in glomerular filtration rate but not with insulin resistance. Exp Clin Endocrinol Diabetes 2006;114:306-309.
38. Ozmen B, Ozmen D, Turgan N, Habif S, Mutaf I, Bayindir O: Association between homocysteinemia and renal function in patients with type 2 diabetes mellitus. Ann Clin Lab Sci 2002;32:279-286.
39. Bostom AG, Bausserman L, Jacques PF, Liaugaudas G, Selhub J, Rosenberg IH: Cystatin C as a determinant of fasting plasma total homocysteine levels in coronary artery disease patients with normal serum creatinine. Arterioscler Thromb Vasc Biol 1999;19:2241-2244.
40. van Guldener C, Donker AJ, Jakobs C, Teerlink T, de Meer K, Stehouwer CD: No net renal extraction of homocysteine in fasting humans. Kidney Int 1998;54:166-169.
41. Guttormsen AB, Ueland PM, Svarstad E, Refsum H: Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997;52:495-502.
42. Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH: The kidney and homocysteine metabolism. J Am Soc Nephrol 2001;12:2181-2189.
43. Ueland PM, Clarke R: Homocysteine and cardiovascular risk: considering the evidence in the context of study design, folate fortification, and statistical power. Clin Chem 2007;53:807-809.
44. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG: MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023-2031.
45. Wilcken DE, Wang J, Sim AS, Green K, Wilcken B: Asymmetric dimethylarginine in homocystinuria due to cystathionine beta-synthase deficiency: relevance of renal function. J Inherit Metab Dis 2006;29:30-37.
46. Brosius FC III, Hostetter TH, Kelepouris E, Mitsnefes MM, Moe SM, Moore MA, Pennathur S, Smith GL, Wilson PW: Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney and Cardiovascular Disease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: developed in collaboration with the National Kidney Foundation. Circulation 2006;114:1083-1087.
47. Abdella N, Mojiminiyi OA, Akanji AO: Homocysteine and endogenous markers of renal function in type 2 diabetic patients without coronary heart disease. Diabetes Res Clin Pract 2000;50:177-185.
48. Ambrosch A, Dierkes J, Lobmann R, Kuhne W, Konig W, Luley C, Lehnert H: Relation between homocysteinaemia and diabetic neuropathy in patients with type 2 diabetes mellitus. Diabet Med 2001;18:185-192.
49. Arnadottir M, Hultberg B, Berg AL: Plasma total homocysteine concentration in nephrotic patients with idiopathic membranous nephropathy. Nephrol Dial Transplant 2001;16:45-47.
50. Arnadottir M, Hultberg B, Vladov V, Nilsson-Ehle P, Thysell H: Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients. Transplantation 1996;61:509-512.
51. Arnadottir M, Hultberg B, Wahlberg J, Fellstrom B, Dimeny E: Serum total homocysteine concentration before and after renal transplantation. Kidney Int 1998;54:1380-1384.
52. Bostom AG, Kronenberg F, Jacques PF, Kuen E, Ritz E, Konig P, Kraatz G, Lhotta K, Mann JF, Muller GA, Neyer U, Riegel W, Schwenger V, Riegler P, Selhub J: Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate. Atherosclerosis 2001;159:219-223.
53. Cossu M, Carru C, Pes GM, Satta R, Mura A, Errigo A, Sanna S, Naitana A, Deiana L, Sorba G, Pinna GG: Plasma homocysteine levels and C677T MTHFR gene polymorphism in stable renal graft recipients. Transplant Proc 2001;33:1156-1158.
54. Dinleyici EC, Kirel B, Alatas O, Muslumanoglu H, Kilic Z, Dogruel N: Plasma total homocysteine levels in children with type 1 diabetes: relationship with vitamin status, methylene tetrahydrofolate reductase genotype, disease parameters and coronary risk factors. J Trop Pediatr 2006;52:260-266.
55. Golubev RV, Blashko EL, Dobronravov VA, Zhloba AA, Smirnov AV: Elevated plasma homocysteine and glutathione level in patients with renal failure. Biomed Khim 2005;51:549-551.
56. Korandji C, Zeller M, Guilland JC, Vergely C, Sicard P, Duvillard L, Gambert P, Moreau D, Cottin Y, Rochette L: Asymmetric dimethylarginine (ADMA) and hyperhomocysteinemia in patients with acute myocardial infarction. Clin Biochem 2007;40:66-72.
57. Krmar RT, Ferraris JR, Ramirez JA, Galarza CR, Waisman G, Janson JJ, Llapur CJ, Sorroche P, Legal S, Camera MI: Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients. Transplantation 2001;71:1748-1751.
58. Lin YH, Pao KY, Wu VC, Lin YL, Chien YF, Hung CS, Chen YJ, Liu CP, Tsai IJ, Gau CS, Wu KD, Hwang JJ: The influence of estimated creatinine clearance on plasma homocysteine in hypertensive patients with normal serum creatinine. Clin Biochem 2007;40:230-234. E-pub 2006.
59. Krzyzanowska K, Mittermayer F, Krugluger W, Schnack C, Hofer M, Wolzt M, Schernthaner G: Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes. Atherosclerosis 2006;189:236-240.
60. Marouf R, Zubaid M, Mojiminiyi OA, Qurtom M, Abdella NA, Al Wazzan H, Al Humood S: Determinants of plasma homocysteine in relation to hematological and biochemical variables in patients with acute myocardial infarction. South Med J 2006;99:811-816.
61. Marouf R, Mojiminiyi O, Qurtom M, Abdella N, Al Wazzan H, Al Humood S, Al Mazeedy M: Plasma homocysteine and hematological factors in patients with venous thromboembolic diseases in Kuwait. Acta Haematol 2006;117:98-105.
62. Marcucci R, Zanazzi M, Bertoni E, Brunelli T, Fedi S, Evangelisti L, Pepe G, Rogolino A, Prisco D, Abbate R, Gensini GF, Salvadori M: Risk factors for cardiovascular disease in renal transplant recipients: new insights. Transpl Int 2000;13(suppl 1):S419-S424.
63. Marcucci R, Fedi S, Brunelli T, Pepe G, Prisco D, Rosati A, Zanazzi M, Bertoni E, Abbate R, Salvadori M: High cysteine levels in renal transplant recipients: relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism. Transplantation 2001;71:746-751.
64. Meinitzer A, Seelhorst U, Wellnitz B, Halwachs-Baumann G, Boehm BO, Winkelmann BR, Marz W: Asymmetrical dimethylarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study). Clin Chem 2006;53:273-278.
65. Ndrepepa G, Kastrati A, Braun S, Koch W, Kolling K, Mehilli J, Schomig A: Circulating homocysteine levels in patients with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2008;18:66-73.
66. Nerbass FB, Draibe SA, Feiten SF, Chiarello PG, Vannucchi H, Cuppari L: Homocysteine and its determinants in nondialyzed chronic kidney disease patients. J Am Diet Assoc 2006;106:267-270.
67. Okumura K, Aso Y: High plasma homocysteine concentrations are associated with plasma concentrations of thrombomodulin in patients with type 2 diabetes and link diabetic nephropathy to macroangiopathy. Metabolism 2003;52:1517-1522.
68. Parsons DS, Reaveley DA, Pavitt DV, Brown EA: Relationship of renal function to homocysteine and lipoprotein(a) levels: the frequency of the combination of both risk factors in chronic renal impairment. Am J Kidney Dis 2002;40:916-923.
69. Pizzolo F, Friso S, Olivieri O, Martinelli N, Bozzini C, Guarini P, Trabetti E, Faccini G, Corrocher R, Girelli D: Homocysteine, traditional risk factors and impaired renal function in coronary artery disease. Eur J Clin Invest 2006;36:698-704.
70. Preston E, Ellis MR, Kulinskaya E, Davies AH, Brown EA: Association between carotid artery intima-media thickness and cardiovascular risk factors in CKD. Am J Kidney Dis 2005;46:856-862.
71. Ravani P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C: Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J Am Soc Nephrol 2005;16:2449-2455.
72. Samuelsson O, Lee DM, Attman PO, Knight-Gibson C, Mullen JK, Larsson R, Mulec H, Weiss L, Alaupovic P: The plasma levels of homocysteine are elevated in moderate renal insufficiency but do not predict the rate of progression. Nephron 1999;82:306-311.
73. Sarnak MJ, Wang SR, Beck GJ, Kusek JW, Selhub J, Greene T, Levey AS: Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression. Am J Kidney Dis 2002;40:932-939.
74. Serafinowicz A, Kukula K, Cieciura T, Shaibani B, Baczkowska T, Soin J, Sadowska A, Nowacka-Cieciura E, Lewandowska D, Rell K, Durlik M, Lao M: Homocysteine and lipid peroxidation products: important atherosclerosis risk factors in renal allograft recipients? Transplant Proc 2000;32:1367-1368.
75. Soedamah-Muthu SS, Chaturvedi N, Teerlink T, Idzior-Walus B, Fuller JH, Stehouwer CD: Plasma homocysteine and microvascular and macrovascular complications in type 1 diabetes: a cross-sectional nested case-control study. J Intern Med 2005;258:450-459.
76. Suliman M, Stenvinkel P, Qureshi AR, Kalantar-Zadeh K, Barany P, Heimburger O, Vonesh EF, Lindholm B: The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation. Nephrol Dial Transplant 2007;22:209-217.
77. Veldman BA, Vervoort G, Blom H, Smits P: Reduced plasma total homocysteine concentrations in type 1 diabetes mellitus is determined by increased renal clearance. Diabet Med 2005;22:301-305.
78. Wang J, Sim AS, Wang XL, Salonikas C, Naidoo D, Wilcken DE: Relations between plasma asymmetric dimethylarginine (ADMA) and risk factors for coronary disease. Atherosclerosis 2006;184:383-388.
79. Widiana IG, Suwitra K: Relationship between creatinine clearance and plasma homocysteine levels in predialytic chronic renal failure patients. Acta Med Indones 2004;36:15-18.
80. Wollesen F, Brattstrom L, Refsum H, Ueland PM, Berglund L, Berne C: Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999;55:1028-1035.
81. Zebrack JS, Anderson JL, Beddhu S, Horne BD, Bair TL, Cheung A, Muhlestein JB: Do associations with C-reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency? J Am Coll Cardiol 2003;42:57-63.