Journal of Renal Nutrition
Volume 20, Issue 2 , Pages 74-81 , March 2010

Serum Carboxymethyl-Lysine, a Dominant Advanced Glycation End Product, Is Associated With Chronic Kidney Disease: The Baltimore Longitudinal Study of Aging

  • Richard D. Semba, MD, MPH

      Affiliations

    • Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland
    • Corresponding Author InformationAddress reprint requests to Richard Semba, MD, MPH, Department of Ophthalmology, Johns Hopkins University School of Medicine, 550 N. Broadway, Suite 700, Baltimore, MD 21205.
  • ,
  • Jeffrey C. Fink, MD, MS

      Affiliations

    • Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
  • ,
  • Kai Sun, MS

      Affiliations

    • Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • ,
  • B. Gwen Windham, MD, MHS

      Affiliations

    • Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland
  • ,
  • Luigi Ferrucci, MD, PhD

      Affiliations

    • Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland

References 

  1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–2047
  2. Schiffrin EL, Lipman ML, Mann JFE. Chronic kidney disease: effects on the cardiovascular system. Circulation. 2007;116:85–97
  3. Vlassara H, Striker G. Glycotoxins in the diet promote diabetes and diabetic complications. Curr Diabetes Rep. 2007;7:235–241
  4. Basta G, Schmidt AM, de Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63:582–592
  5. Bohlender JM, Franke S, Stein G, et al. Advanced glycation end products and the kidney. Am J Renal Physiol. 2005;289:F645–F659
  6. Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product Nε-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest. 1997;99:457–468
  7. Goldberg T, Cai W, Peppa M, et al. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc. 2004;104:1287–1291
  8. Koschinsky T, He CJ, Mitsuhashi T, et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA. 1997;94:6474–6479
  9. Vlassara H, Cai W, Crandall J, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA. 2002;99:15596–15601
  10. Uribarri J, Peppa M, Cai W, et al. Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. Am J Kidney Dis. 2003;42:532–538
  11. Negrean M, Stirban A, Stratmann B, et al. Effects of low- and high-advanced glycation endproduct meals on macro- and microvascular endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Clin Nutr. 2007;85:1236–1243
  12. Kass DA, Shapiro EP, Kawaguchi M, et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 2001;104:1464–1470
  13. Little WC, Zile MR, Kitzman DW, et al. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005;11:191–195
  14. Bolton WK, Cattran DC, Williams ME, et al. Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am J Nephrol. 2004;24:32–40
  15. Williams ME, Bolton WK, Khalifah RG, et al. 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
  16. Degenhardt TP, Alderson NL, Arrington DD, et al. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int. 2002;61:939–950
  17. Forbes JM, Thallas V, Thomas MC, et al. The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J. 2003;17:1762–1764
  18. Susic D, Varagic J, Ahn J, et al. Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats. Am J Hypertens. 2004;17:328–333
  19. Miyata T, Kurokawa K, van Ypersele de Strihou C. Relevance of oxidative and carbonyl stress to long-term uremic complications. Kidney Int. 2000;76(Suppl):S120–S125
  20. Basta G. Receptor for advanced glycation endproducts and atherosclerosis: from basic mechanisms to clinical implications. Atherosclerosis. 2008;196:9–21
  21. Shock NW, Greulich RC, Andres RA, et al. Normal Human Aging: The Baltimore Longitudinal Study of Aging. Washington, DC: U.S. Government Printing Office; 1984;
  22. Reddy S, Bichler J, Wells-Knecht KJ, et al. N epsilon-(carboxymethyl)lysine is a dominant advanced glycation end product (AGE) antigen in tissue proteins. Biochemistry. 1995;34:10872–10878
  23. Boehm BO, Schilling S, Rosinger S, et al. Elevated serum levels of Nε-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema. Diabetologia. 2004;47:1376–1379
  24. Zhang X, Frischmann M, Kientsch-Engel R, et al. Two immunochemical assays to measure advanced glycation end-products in serum from dialysis patients. Clin Chem Lab Med. 2005;43:503–511
  25. James PT, Leach R, Kalamara E, et al. The worldwide obesity epidemic. Obes Res. 2001;9(Suppl 4):228S–233S
  26. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137–147
  27. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130:461–470
  28. Forbes JM, Thorpe SR, Thallas-Bonke V, et al. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol. 2005;16:2363–2372
  29. Makita Z, Radoff S, Rayfield EJ, et al. Advanced glycosylation end-products in patients with diabetic nephropathy. N Engl J Med. 1991;325:836–842
  30. Mostafa AA, Randell EW, Vasdev SC, et al. Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes. Mol Cell Biochem. 2007;302:35–42
  31. Miyata T, Ueda Y, Shinzato T, et al. Accumulation of albumin-linked and free-form pentosidine in the circulation of uremic patients with end-stage renal failure: renal implications in the pathophysiology of pentosidine. J Am Soc Nephrol. 1996;7:1198–1206
  32. Suliman ME, Heimbürger O, Bárány P, et al. Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy. J Am Soc Nephrol. 2003;14:1614–1422
  33. Wautier MP, Boulanger E, Guillausseau PJ, Massin P, Wauter JL. AGEs, macrophage colony stimulating factor and vascular adhesion molecule blood levels are increased in patients with diabetic microangiopathy. Thromb Haemost. 2004;91:879–885
  34. Gugliucci A, Bendayan M. Renal fate of circulating advanced glycated end products (AGE): evidence for reabsorption and catabolism of AGE-peptides by renal proximal tubular cells. Diabetologia. 1996;39:149–160
  35. Miyata T, Ueda Y, Horie K, et al. Renal catabolism of AGEs: the fate of pentosidine. Kidney Int. 1998;53:416–422
  36. Schinzel R, Münch G, Heidland A, et al. Advanced glycation end products in end-stage renal disease and their removal. Nephron. 2001;87:295–303
  37. Busch M, Franke S, Wolf G, et al. The advanced glycation end product Nε-carboxymethyllysine is not a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension. Am J Kidney Dis. 2006;48:571–579
  38. Vlassara H, Striker LJ, Teichberg S, et al. Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats. Proc Natl Acad Sci USA. 1994;91:11704–11708
  39. Yang CW, Vlassara H, Peten EP, et al. Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease. Proc Natl Acad Sci USA. 1994;91:9436–9440
  40. Bostom A. Homocysteine: “expensive creatinine” or important modifiable risk factor for arteriosclerotic outcomes in renal transplant recipients?. J Am Soc Nephrol. 2000;11:149–151
  41. Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA. 2007;298:1212–1214
  42. Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–772
  43. Uribarri J, Peppa M, Cai W, et al. Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol. 2003;14:728–731

PII: S1051-2276(09)00219-2

doi: 10.1053/j.jrn.2009.08.001

Journal of Renal Nutrition
Volume 20, Issue 2 , Pages 74-81 , March 2010