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Amino Acids

, Volume 42, Issue 4, pp 1185–1192 | Cite as

Glycation in diabetic nephropathy

  • Josephine M. ForbesEmail author
  • Mark E. Cooper
Review Article

Abstract

The kidney is an extremely complex organ with broad ranging functions in the body, including but not restricted to waste excretion, ion and water balance, maintenance of blood pressure, glucose homeostasis, generation of erythropoietin and activation of vitamin D. With diabetes, many of these integral processes are interrupted via a combination of haemodynamic and metabolic changes including increases in the accumulation of proteins modified by advanced glycation, known as advanced glycation end products (AGEs). Indeed, hyperglycaemia and the redox imbalances seen with diabetes are each independent accelerants for the production of AGEs, which synergistically combine in this disorder. In addition, as kidney function declines, characterised by a loss of glomerular filtration, the excretion of AGEs is decreased, possibly exacerbating renal injury by further elevating the body’s tissue and circulating AGE pool. Therefore, it has become apparent that decreasing the accumulation of AGEs or interrupting their downstream effects on the kidney, are desirable therapeutic targets for the treatment of diabetic renal disease.

Keywords

Diabetic nephropathy Advanced glycation Haemodynamic Renal 

References

  1. Alkhalaf A, Klooster A, van Oeveren W, Achenbach U, Kleefstra N, Slingerland RJ, Mijnhout GS, Bilo HJ, Gans RO, Navis GJ, Bakker SJ (2010) A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care 33(7):1598–1601PubMedCrossRefGoogle Scholar
  2. Appel G, Bolton K, Freedman B, Wuerth J, C K (1999) Pimagedine (pg) lowers total urinary toal protein (tup) and slows progression of overt diabetes in patients with type 1 diabetes mellitus (dm). J Am Soc Nephrol 10:153AGoogle Scholar
  3. Babaei-Jadidi R, Karachalias N, Ahmed N, Battah S, Thornalley PJ (2003) Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 52(8):2110–2120PubMedCrossRefGoogle Scholar
  4. Babu PV, Sabitha KE, Shyamaladevi CS (2008) Effect of green tea extract on advanced glycation and cross-linking of tail tendon collagen in streptozotocin induced diabetic rats. Food Chem Toxicol 46(1):280–285PubMedCrossRefGoogle Scholar
  5. Bardoux P, Bichet DG, Martin H, Gallois Y, Marre M, Arthus MF, Lonergan M, Ruel N, Bouby N, Bankir L (2003) Vasopressin increases urinary albumin excretion in rats and humans: involvement of v2 receptors and the renin–angiotensin system. Nephrol Dial Transplant 18(3):497–506PubMedCrossRefGoogle Scholar
  6. Basta G, Sironi AM, Lazzerini G, Del Turco S, Buzzigoli E, Casolaro A, Natali A, Ferrannini E, Gastaldelli A (2006) Circulating soluble receptor for advanced glycation end products is inversely associated with glycemic control and s100a12 protein. J Clin Endocrinol Metab 91(11):4628–4634PubMedCrossRefGoogle Scholar
  7. Beisswenger BG, Delucia EM, Lapoint N, Sanford RJ, Beisswenger PJ (2005) Ketosis leads to increased methylglyoxal production on the atkins diet. Ann N Y Acad Sci 1043:201–210PubMedCrossRefGoogle Scholar
  8. Boor P, Celec P, Behuliak M, Grancic P, Kebis A, Kukan M, Pronayova N, Liptaj T, Ostendorf T, Sebekova K (2009) Regular moderate exercise reduces advanced glycation and ameliorates early diabetic nephropathy in obese zucker rats. Metabolism 58(11):1669–1677PubMedCrossRefGoogle Scholar
  9. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345(12):861–869PubMedCrossRefGoogle Scholar
  10. Bryszewska M, Szosland K (1988) Association between the glycation of erythrocyte membrane proteins and membrane fluidity. Clin Biochem 21(1):49–51PubMedCrossRefGoogle Scholar
  11. Cao Z, Kelly DJ, Cox A, Casley D, Forbes JM, Martinello P, Dean R, Gilbert RE, Cooper ME (2000) Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis. Kidney Int 58(6):2437–2451PubMedCrossRefGoogle Scholar
  12. Charonis AS, Reger LA, Dege JE, Kouzi-Koliakos K, Furcht LT, Wohlhueter RM, Tsilibary EC (1990) Laminin alterations after in vitro nonenzymatic glycosylation. Diabetes 39(7):807–814PubMedCrossRefGoogle Scholar
  13. Cooper ME (1998) Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet 352(9123):213–219PubMedCrossRefGoogle Scholar
  14. Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan AL, Fukami K, Thallas-Bonke V, Nawroth PP, Brownlee M, Bierhaus A, Cooper ME, Forbes JM (2009) Rage-induced cytosolic ros promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol 20(4):742–752PubMedCrossRefGoogle Scholar
  15. de Gasparo M, Husain A, Alexander W, Catt KJ, Chiu AT, Drew M, Goodfriend T, Harding JW, Inagami T, Timmermans PB (1995) Proposed update of angiotensin receptor nomenclature. Hypertension 25(5):924–927PubMedGoogle Scholar
  16. Degenhardt TP, Alderson NL, Arrington DD, Beattie RJ, Basgen JM, Steffes MW, Thorpe SR, Baynes JW (2002) Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int 61(3):939–950PubMedCrossRefGoogle Scholar
  17. Flyvbjerg A, Denner L, Schrijvers BF, Tilton RG, Mogensen TH, Paludan SR, Rasch R (2004) Long-term renal effects of a neutralizing rage antibody in obese type 2 diabetic mice. Diabetes 53(1):166–172PubMedCrossRefGoogle Scholar
  18. Forbes JM, Cooper ME, Oldfield MD, Thomas MC (2003a) Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol 14 (8 Suppl 3):S254–S258CrossRefGoogle Scholar
  19. Forbes JM, Thallas V, Thomas MC, Founds HW, Burns WC, Jerums G, Cooper ME (2003b) The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. Faseb J 17(12):1762–1764PubMedGoogle Scholar
  20. Forbes JM, Thorpe SR, Thallas-Bonke V, Pete J, Thomas MC, Deemer ER, Bassal S, El-Osta A, Long DM, Panagiotopoulos S, Jerums G, Osicka TM, Cooper ME (2005) Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol 16(8):2363–2372PubMedCrossRefGoogle Scholar
  21. Friess U, Waldner M, Wahl HG, Lehmann R, Haring HU, Voelter W, Schleicher E (2003) Liquid chromatography-based determination of urinary free and total n(epsilon)-(carboxymethyl)lysine excretion in normal and diabetic subjects. J Chromatogr B Analyt Technol Biomed Life Sci 794(2):273–280PubMedCrossRefGoogle Scholar
  22. Fukami K, Ueda S, Yamagishi S, Kato S, Inagaki Y, Takeuchi M, Motomiya Y, Bucala R, Iida S, Tamaki K, Imaizumi T, Cooper ME, Okuda S (2004) Ages activate mesangial TGF-beta-Smad signalling via an angiotensin II type 1 receptor interaction. Kidney Int 66(6):2137–2147PubMedCrossRefGoogle Scholar
  23. Gallicchio MA, Bach LA (2010) Advanced glycation end products inhibit na(+) k(+) atpase in proximal tubule epithelial cells: role of cytosolic phospholipase a(2)alpha and phosphatidylinositol 4-phosphate 5-kinase gamma. Biochim Biophys Acta 1803(8):919–930PubMedCrossRefGoogle Scholar
  24. Groop PH, Thomas MC, Moran JL, Waden J, Thorn LM, Makinen VP, Rosengard-Barlund M, Saraheimo M, Hietala K, Heikkila O, Forsblom C (2009) The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes 58(7):1651–1658PubMedCrossRefGoogle Scholar
  25. Han HJ, Lee YJ, Park SH, Lee JH, Taub M (2005) High glucose-induced oxidative stress inhibits Na+/glucose cotransporter activity in renal proximal tubule cells. Am J Physiol Renal Physiol 288(5):F988–F996PubMedCrossRefGoogle Scholar
  26. Han Y, Randell E, Vasdev S, Gill V, Gadag V, Newhook LA, Grant M, Hagerty D (2007) Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with type 1 diabetes. Mol Cell Biochem 305(1–2):123–131PubMedCrossRefGoogle Scholar
  27. Heierli C, Tholen H (1981) Metabolites of glucose in the blood of patients with renal failure. Klin Wochenschr 59(9):431–436PubMedCrossRefGoogle Scholar
  28. House AA, Eliasziw M, Cattran DC, Churchill DN, Oliver MJ, Fine A, Dresser GK, Spence JD (2010) Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA 303(16):1603–1609PubMedCrossRefGoogle Scholar
  29. Humpert PM, Djuric Z, Kopf S, Rudofsky G, Morcos M, Nawroth PP, Bierhaus A (2007) Soluble rage but not endogenous secretory rage is associated with albuminuria in patients with type 2 diabetes. Cardiovasc Diabetol 6:9PubMedCrossRefGoogle Scholar
  30. Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377(6551):748–750PubMedCrossRefGoogle Scholar
  31. JCT Pope, Nishimura H, Ichikawa I (1998) Role of angiotensin in the development of the kidney and urinary tract. Nephrologie 19(7):433–436Google Scholar
  32. Kilhovd BK, Giardino I, Torjesen PA, Birkeland KI, Berg TJ, Thornalley PJ, Brownlee M, Hanssen KF (2003) Increased serum levels of the specific age-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes. Metabolism 52(2):163–167PubMedCrossRefGoogle Scholar
  33. Krishnamurti U, Rondeau E, Sraer JD, Michael AF, Tsilibary EC (1997) Alterations in human glomerular epithelial cells interacting with nonenzymatically glycosylated matrix. J Biol Chem 272(44):27966–27970PubMedCrossRefGoogle Scholar
  34. Levi V, Villamil Giraldo AM, Castello PR, Rossi JP, Gonzalez Flecha FL (2008) Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability. Biochem J 416(1):145–152PubMedCrossRefGoogle Scholar
  35. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The collaborative study group. N Engl J Med 329 (20):1456–1462CrossRefGoogle Scholar
  36. List JF, Woo V, Morales E, Tang W, Fiedorek FT (2009) Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32(4):650–657PubMedCrossRefGoogle Scholar
  37. Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney V, Friedman EA, Cerami A, Vlassara H (1991) Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 325(12):836–842PubMedCrossRefGoogle Scholar
  38. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375(9731):2073–2081PubMedCrossRefGoogle Scholar
  39. Mauer SM, Steffes MW, Michael AF, Brown DM (1976) Studies of diabetic nephropathy in animals and man. Diabetes 25(Suppl 2):850–857PubMedGoogle Scholar
  40. Miyata T, de Strihou CY (2010) Diabetic nephropathy: a disorder of oxygen metabolism? Nat Rev Nephrol 6(2):83–95PubMedCrossRefGoogle Scholar
  41. Miyata T, Notoya K, Yoshida K, Horie K, Maeda K, Kurokawa K, Taketomi S (1997) Advanced glycation end products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalized bone particles. J Am Soc Nephrol 8(2):260–270PubMedGoogle Scholar
  42. Mortensen HB (1985) Glycated hemoglobin. Reaction and biokinetic studies. Clinical application of hemoglobin a1c in the assessment of metabolic control in children with diabetes mellitus. Dan Med Bull 32 (6):309–328Google Scholar
  43. Nakamura S, Makita Z, Ishikawa S, Yasumura K, Fujii W, Yanagisawa K, Kawata T, Koike T (1997) Progression of nephropathy in spontaneous diabetic rats is prevented by opb-9195, a novel inhibitor of advanced glycation. Diabetes 46(5):895–899PubMedCrossRefGoogle Scholar
  44. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM (1997) Expression of the subtype 2 angiotensin (at2) receptor protein in rat kidney. Hypertension 30(5):1238–1246PubMedGoogle Scholar
  45. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH (1996) The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med 124(7):627–632PubMedGoogle Scholar
  46. Penfold SA, Coughlan MT, Patel SK, Srivastava PM, Sourris KC, Steer D, Webster DE, Thomas MC, MacIsaac RJ, Jerums G, Burrell LA, Cooper ME, Forbes JM (2010) Circulating high molecular weight rage ligands activate pathogenic pathways implicated in the development diabetic nephropathy. Kidney Int 2nd February (in Press)Google Scholar
  47. Ruster C, Bondeva T, Franke S, Tanaka N, Yamamoto H, Wolf G (2009) Angiotensin II upregulates rage expression on podocytes: role of AT2 receptors. Am J Nephrol 29(6):538–550PubMedCrossRefGoogle Scholar
  48. Santana RB, Xu L, Chase HB, Amar S, Graves DT, Trackman PC (2003) A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes 52(6):1502–1510PubMedCrossRefGoogle Scholar
  49. Sebekova K, Somoza V, Jarcuskova M, Heidland A, Podracka L (2009) Plasma advanced glycation end products are decreased in obese children compared with lean controls. Int J Pediatr Obes 4(2):112–118PubMedCrossRefGoogle Scholar
  50. Shaw SS, Schmidt AM, Banes AK, Wang X, Stern DM, Marrero MB (2003) S100B-RAGE-mediated augmentation of angiotensin ii-induced activation of JAK2 in vascular smooth muscle cells is dependent on PLD2. Diabetes 52(9):2381–2388PubMedCrossRefGoogle Scholar
  51. Singh DK, Winocour P, Farrington K (2008) Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol 4(4):216–226PubMedCrossRefGoogle Scholar
  52. Singh DK, Winocour P, Farrington K (2009) Erythropoietic stress and anemia in diabetes mellitus. Nat Rev Endocrinol 5(4):204–210PubMedCrossRefGoogle Scholar
  53. Siragy HM, Carey RM (1997) The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 100(2):264–269PubMedCrossRefGoogle Scholar
  54. Soulisliparota T, Cooper ME, Dunlop M, Jerums G (1995) The relative roles of advanced glycation, oxidation and aldose reductase inhibition in the development of experimental diabetic nephropathy in the sprague-dawley rat. Diabetologia 38(4):387–394CrossRefGoogle Scholar
  55. Soulis-Liparota T, Cooper M, Papazoglou D, Clarke B, Jerums G (1991) Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes 40(10):1328–1334PubMedCrossRefGoogle Scholar
  56. Sourris KC, Harcourt BE, Forbes JM (2009) A new perspective on therapeutic inhibition of advanced glycation in diabetic microvascular complications: common downstream endpoints achieved through disparate therapeutic approaches? Am J Nephrol 30(4):323–335PubMedCrossRefGoogle Scholar
  57. Sourris KC, Morley AL, Koitka A, Samuel P, Coughlan MT, Penfold SA, Thomas MC, Bierhaus A, Nawroth P, Yamamoto H, Allen TJ, Walther T, Hussain T, Cooper ME, Forbes JM (2010) Receptor for ages (rage) blockade may exert its renoprotective effects in patients with diabetic nephropathy via induction of the angiotensin ii type 2 (at2) receptor DiabetologiaGoogle Scholar
  58. Suzuki D, Miyata T, Saotome N, Horie K, Inagi R, Yasuda Y, Uchida K, Izuhara Y, Yagame M, Sakai H, Kurokawa K (1999) Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 10(4):822–832PubMedGoogle Scholar
  59. Talmor Y, Golan E, Benchetrit S, Bernheim J, Klein O, Green J, Rashid G (2008) Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells. Am J Physiol Renal Physiol 294(5):F1059–F1064PubMedCrossRefGoogle Scholar
  60. Tan AL, Sourris KC, Harcourt BE, Thallas-Bonke V, Penfold S, Andrikopoulos S, Thomas MC, O’Brien RC, Bierhaus A, Cooper ME, Forbes JM, Coughlan MT (2010) Disparate effects on renal and oxidative parameters following rage deletion, age accumulation inhibition, or dietary age control in experimental diabetic nephropathy. Am J Physiol Renal Physiol 298(3):F763–F770PubMedCrossRefGoogle Scholar
  61. Tarelli E, Corran PH, Bingham BR, Mollison H, Wait R (1994) Lysine vasopressin undergoes rapid glycation in the presence of reducing sugars. J Pharm Biomed Anal 12(11):1355–1361PubMedCrossRefGoogle Scholar
  62. Tarsio JF, Wigness B, Rhode TD, Rupp WM, Buchwald H, Furcht LT (1985) Nonenzymatic glycation of fibronectin and alterations in the molecular association of cell matrix and basement membrane components in diabetes mellitus. Diabetes 34(5):477–484PubMedCrossRefGoogle Scholar
  63. Thomas MC, Tikellis C, Burns WM, Bialkowski K, Cao Z, Coughlan MT, Jandeleit-Dahm K, Cooper ME, Forbes JM (2005) Interactions between renin angiotensin system and advanced glycation in the kidney. J Am Soc Nephrol 16(10):2976–2984PubMedCrossRefGoogle Scholar
  64. Turgut F, Bolton WK (2010) Potential new therapeutic agents for diabetic kidney disease. Am J Kidney Dis 55(5):928–940PubMedCrossRefGoogle Scholar
  65. Uk prospective diabetes study group (1998) Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: Ukpds 38. BMJ 317 (7160):703–713Google Scholar
  66. Unlucerci Y, Kocak H, Seferoglu G, BekpInar S (2001) The effect of aminoguanidine on diabetes-induced inactivation of kidney na(+), k(+)- atpase in rats. Pharmacol Res 44(2):95–98PubMedCrossRefGoogle Scholar
  67. Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarelli LG, Rong LL, Moser B, Markowitz GS, Stein G, Bierhaus A, Liliensiek B, Arnold B, Nawroth PP, Stern DM, D’Agati VD, Schmidt AM (2003) Rage drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 162(4):1123–1137PubMedCrossRefGoogle Scholar
  68. Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB (2007) Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 27(6):605–614PubMedCrossRefGoogle Scholar
  69. Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, Watanabe T, Yamagishi S, Sakurai S, Takasawa S, Okamoto H, Yamamoto H (2001) Development and prevention of advanced diabetic nephropathy in rage-overexpressing mice. J Clin Invest 108(2):261–268PubMedGoogle Scholar
  70. Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, Yasui K, Takeuchi M, Makita Z, Takasawa S, Okamoto H, Watanabe T, Yamamoto H (2003) Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J 370(Pt 3):1097–1109PubMedCrossRefGoogle Scholar
  71. Zheng F, He C, Cai W, Hattori M, Steffes M, Vlassara H (2002) Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products. Diabetes Metab Res Rev 18(3):224–237PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Division of Diabetes ComplicationsGlycation and Diabetes, Baker IDI Heart and Diabetes InstituteMelbourneAustralia
  2. 2.Department of Medicine and Immunology, Alfred Hospital Medical Research and Education PrecinctMonash UniversityMelbourneAustralia

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