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The Axis AGE-RAGE-Soluble RAGE and Oxidative Stress in Chronic Kidney Disease

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Oxidative Stress and Inflammation in Non-communicable Diseases - Molecular Mechanisms and Perspectives in Therapeutics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 824))

Abstract

Chronic kidney disease (CKD) has been shown to be associated with high oxidative stress and cardiovascular disease. In this chapter our focus will be on the role of advanced glycation end products (AGE) and their receptor, RAGE in CKD progression and their role on cardiovascular complications. We provide a succinct, yet comprehensive summary of the current knowledge, the challenges and the future therapeutic avenues that are stemming out from novel recent findings. We first briefly review glycation and AGE formation and the role of the kidney in their metabolism. Next, we focus on the RAGE, its signaling and role in oxidative stress. We address the possible role of soluble RAGEs as decoys and the controversy regarding this issue. We then provide the latest information on the specific role of both AGE and RAGE in inflammation and perpetuation of kidney damage in diabetes and in CKD without diabetes, which is the main purpose of the review. Finally, we offer an update on new avenues to target the AGE-RAGE axis in CKD.

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References

  1. Smit AJ, Gerrits EG. Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease. Curr Opin Nephrol Hypertens. 2010;19:527–33.

    CAS  PubMed  Google Scholar 

  2. Koyama H, Nishizawa Y. AGEs/RAGE in CKD: irreversible metabolic memory road toward CVD? Eur J Clin Invest. 2010;40:623–35.

    CAS  PubMed  Google Scholar 

  3. Thallas-Bonke V, Coughlan MT, Tan AL, Harcourt BE, Morgan PE, Davies MJ, et al. Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content. Nephrology (Carlton). 2013;18:47–56.

    CAS  Google Scholar 

  4. Arsov S, Graaff R, van Oeveren W, Stegmayr B, Sikole A, Rakhorst G, et al. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review. Clin Chem Lab Med. 2013;4:1–10.

    Google Scholar 

  5. Yamagishi S, Matsui T. Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxid Med Cell Longev. 2010;3:101–8.

    PubMed Central  PubMed  Google Scholar 

  6. Schmidt AM, Stern D. Atherosclerosis and diabetes: the RAGE connection. Curr Atheroscler Rep. 2000;2:430–6.

    CAS  PubMed  Google Scholar 

  7. Jerums G, Panagiotopoulos S, Forbes J, Osicka T, Cooper M. Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease. Arch Biochem Biophys. 2003;419:55–62.

    CAS  PubMed  Google Scholar 

  8. Heidland A, Sebekova K, Schinzel R. Advanced glycation end products and the progressive course of renal disease. Am J Kidney Dis. 2001;38(4 Suppl 1):S100–6.

    CAS  PubMed  Google Scholar 

  9. Vlassara H. Protein glycation in the kidney: role in diabetes and aging. Kidney Int. 1996;49:1795–804.

    CAS  PubMed  Google Scholar 

  10. 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;39:149–60.

    CAS  PubMed  Google Scholar 

  11. Vlassara H. Advanced glycation in diabetic renal and vascular disease. Kidney Int Suppl. 1995;51:S43–4.

    CAS  PubMed  Google Scholar 

  12. Dyer DG, Blackledge JA, Katz BM, Hull CJ, Adkisson HD, Thorpe SR, et al. The Maillard reaction in vivo. Z Ernahrungswiss. 1991;30:29–45.

    CAS  PubMed  Google Scholar 

  13. Mullarkey CJ, Edelstein D, Brownlee M. Free radical generation by early glycation products: a mechanism for accelerated atherogenesis in diabetes. Biochem Biophys Res Commun. 1990;173:932–9.

    CAS  PubMed  Google Scholar 

  14. Watkins NG, Neglia-Fisher CI, Dyer DG, Thorpe SR, Baynes JW. Effect of phosphate on the kinetics and specificity of glycation of protein. J Biol Chem. 1987;262:7207–12.

    CAS  PubMed  Google Scholar 

  15. Thornalley PJ. Advanced glycation end products in renal failure. J Ren Nutr. 2006;16:178–84.

    PubMed  Google Scholar 

  16. Thornalley PJ. Glycation free adduct accumulation in renal disease: the new AGE. Pediatr Nephrol. 2005;20:1515–22.

    PubMed  Google Scholar 

  17. Brouwers O, Niessen PM, Miyata T, Ostergaard JA, Flyvbjerg A, Peutz-Kootstra CJ, et al. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes. Diabetologia. 2014;57:224–35.

    CAS  PubMed  Google Scholar 

  18. Vlassara H, Torreggiani M, Post JB, Zheng F, Uribarri J, Striker GE. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging. Kidney Int Suppl. 2009;114:S3–11.

    CAS  PubMed  Google Scholar 

  19. Linden E, Cai W, He JC, Xue C, Li Z, Winston J, et al. Endothelial dysfunction in patients with chronic kidney disease results from advanced glycation end products (AGE)-mediated inhibition of endothelial nitric oxide synthase through RAGE activation. Clin J Am Soc Nephrol. 2008;3:691–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, He C, et al. Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol. 2003;14:728–31.

    CAS  PubMed  Google Scholar 

  21. Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, Baliga S, et al. Dietary glycotoxins correlate with circulating advanced glycation end product levels in renal failure patients. Am J Kidney Dis. 2003;42:532–8.

    CAS  PubMed  Google Scholar 

  22. Gugliucci A, Bendayan M. Reaction of advanced glycation endproducts with renal tissue from normal and streptozotocin-induced diabetic rats: an ultrastructural study using colloidal gold cytochemistry. J Histochem Cytochem. 1995;43:591–600.

    CAS  PubMed  Google Scholar 

  23. Popolo A, Autore G, Pinto A, Marzocco S. Oxidative stress in patients with cardiovascular disease and chronic renal failure. Free Radic Res. 2013;47:346–56.

    CAS  PubMed  Google Scholar 

  24. Bowman MA, Schmidt AM. The next generation of RAGE modulators: implications for soluble RAGE therapies in vascular inflammation. J Mol Med (Berl). 2013;91:1329–31.

    Google Scholar 

  25. Ramasamy R, Yan SF, Schmidt AM. Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids. 2012;42:1151–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Monnier VM, Sell DR, Nagaraj RH, Miyata S, Grandhee S, Odetti P, et al. Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes. 1992;41 Suppl 2:36–41.

    CAS  PubMed  Google Scholar 

  27. Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR, et al. Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Invest. 1993;91:2463–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Lee AT, Cerami A. Role of glycation in aging. Ann N Y Acad Sci. 1992;663:63–70.

    CAS  PubMed  Google Scholar 

  29. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T, Cerami A, et al. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci U S A. 1994;91:9441–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Cerami C, Founds H, Nicholl I, Mitsuhashi T, Giordano D, Vanpatten S, et al. Tobacco smoke is a source of toxic reactive glycation products. Proc Natl Acad Sci U S A. 1997;94:13915–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Thornalley PJ, Rabbani N. Highlights and hotspots of protein glycation in end-stage renal disease. Semin Dial. 2009;22:400–4.

    PubMed  Google Scholar 

  32. Grandhee SK, Monnier VM. Mechanism of formation of the Maillard protein cross-link pentosidine. Glucose, fructose, and ascorbate as pentosidine precursors. J Biol Chem. 1991;266:11649–53.

    CAS  PubMed  Google Scholar 

  33. Sell DR, Nagaraj RH, Grandhee SK, Odetti P, Lapolla A, Fogarty J, et al. Pentosidine: a molecular marker for the cumulative damage to proteins in diabetes, aging, and uremia. Diabetes Metab Rev. 1991;7:239–51.

    CAS  PubMed  Google Scholar 

  34. Hricik DE, Schulak JA, Sell DR, Fogarty JF, Monnier VM. Effects of kidney or kidney-pancreas transplantation on plasma pentosidine. Kidney Int. 1993;43:398–403.

    CAS  PubMed  Google Scholar 

  35. Agalou S, Ahmed N, Babaei-Jadidi R, Dawnay A, Thornalley PJ. Profound mishandling of protein glycation degradation products in uremia and dialysis. J Am Soc Nephrol. 2005;16:1471–85.

    CAS  PubMed  Google Scholar 

  36. Rabbani N, Sebekova K, Sebekova Jr K, Heidland A, Thornalley PJ. Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function. Kidney Int. 2007;72:1113–21.

    CAS  PubMed  Google Scholar 

  37. Rabbani N, Thornalley PJ. Quantitation of markers of protein damage by glycation, oxidation, and nitration in peritoneal dialysis. Perit Dial Int. 2009;29 Suppl 2:S51–6.

    CAS  PubMed  Google Scholar 

  38. Karachalias N, Babaei-Jadidi R, Rabbani N, Thornalley PJ. Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes. Diabetologia. 2010;53:1506–16.

    CAS  PubMed  Google Scholar 

  39. Kihm LP, Muller-Krebs S, Klein J, Ehrlich G, Mertes L, Gross ML, et al. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J Am Soc Nephrol. 2011;22:914–26.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Mallipattu SK, He JC, Uribarri J. Role of advanced glycation endproducts and potential therapeutic interventions in dialysis patients. Semin Dial. 2012;25:529–38.

    PubMed  Google Scholar 

  41. Kim YL, Cho JH, Choi JY, Kim CD, Park SH. Systemic and local impact of glucose and glucose degradation products in peritoneal dialysis solution. J Ren Nutr. 2013;23:218–22.

    CAS  PubMed  Google Scholar 

  42. Vlassara H. Serum advanced glycosylation end products: a new class of uremic toxins? Blood Purif. 1994;12:54–9.

    CAS  PubMed  Google Scholar 

  43. Horl WH. Genesis of the uraemic syndrome: role of uraemic toxins. Wien Klin Wochenschr. 1998;110:511–20.

    CAS  PubMed  Google Scholar 

  44. Gugliucci A, Kinugasa E, Ogata H, Caccavello R, Kimura S. Activation of paraoxonase 1 after hemodialysis is associated with HDL remodeling and its increase in the HDL fraction and VLDL. Clin Chim Acta. 2013;430C:9–14.

    Google Scholar 

  45. Gugliucci A, Mehlhaff K, Kinugasa E, Ogata H, Hermo R, Schulze J, et al. Paraoxonase-1 concentrations in end-stage renal disease patients increase after hemodialysis: correlation with low molecular AGE adduct clearance. Clin Chim Acta. 2007;377:213–20.

    CAS  PubMed  Google Scholar 

  46. Wihler C, Schafer S, Schmid K, Deemer EK, Munch G, Bleich M, et al. Renal accumulation and clearance of advanced glycation end-products in type 2 diabetic nephropathy: effect of angiotensin-converting enzyme and vasopeptidase inhibition. Diabetologia. 2005;48:1645–53.

    CAS  PubMed  Google Scholar 

  47. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–53.

    PubMed  Google Scholar 

  48. Coughlan MT, Mibus AL, Forbes JM. Oxidative stress and advanced glycation in diabetic nephropathy. Ann N Y Acad Sci. 2008;1126:190–3.

    CAS  PubMed  Google Scholar 

  49. Siems W, Quast S, Carluccio F, Wiswedel I, Hirsch D, Augustin W, et al. Oxidative stress in chronic renal failure as a cardiovascular risk factor. Clin Nephrol. 2002;58 Suppl 1:S12–9.

    CAS  PubMed  Google Scholar 

  50. Massy ZA, Nguyen-Khoa T. Oxidative stress and chronic renal failure: markers and management. J Nephrol. 2002;15:336–41.

    CAS  PubMed  Google Scholar 

  51. Miyata T, Hori O, Zhang J, Yan SD, Ferran L, Iida Y, et al. The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis. J Clin Invest. 1996;98:1088–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Schmidt AM, Hori O, Cao R, Yan SD, Brett J, Wautier JL, et al. RAGE: a novel cellular receptor for advanced glycation end products. Diabetes. 1996;45 Suppl 3:S77–80.

    CAS  PubMed  Google Scholar 

  53. Tanji N, Markowitz GS, Fu C, Kislinger T, Taguchi A, Pischetsrieder M, et al. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J Am Soc Nephrol. 2000;11:1656–66.

    CAS  PubMed  Google Scholar 

  54. Yamagishi S, Takeuchi M, Inagaki Y, Nakamura K, Imaizumi T. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy. Int J Clin Pharmacol Res. 2003;23:129–34.

    CAS  PubMed  Google Scholar 

  55. Rodriguez-Ayala E, Anderstam B, Suliman ME, Seeberger A, Heimburger O, Lindholm B, et al. Enhanced RAGE-mediated NFkappaB stimulation in inflamed hemodialysis patients. Atherosclerosis. 2005;180:333–40.

    CAS  PubMed  Google Scholar 

  56. Coughlan MT, Cooper ME, Forbes JM. Renal microvascular injury in diabetes: RAGE and redox signaling. Antioxid Redox Signal. 2007;9:331–42.

    CAS  PubMed  Google Scholar 

  57. Daffu G, del Pozo CH, O’Shea KM, Ananthakrishnan R, Ramasamy R, Schmidt AM. Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases and beyond. Int J Mol Sci. 2013;14:19891–910.

    PubMed Central  PubMed  Google Scholar 

  58. Zhou LL, Cao W, Xie C, Tian J, Zhou Z, Zhou Q, et al. The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis. Kidney Int. 2012;82:759–70.

    CAS  PubMed  Google Scholar 

  59. Yamamoto Y, Yamamoto H. Interaction of receptor for advanced glycation end products with advanced oxidation protein products induces podocyte injury. Kidney Int. 2012;82:733–5.

    CAS  PubMed  Google Scholar 

  60. Ramasamy R, Yan SF, Schmidt AM. Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann N Y Acad Sci. 2011;1243:88–102.

    CAS  PubMed  Google Scholar 

  61. Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 2010;106:842–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Reiniger N, Lau K, McCalla D, Eby B, Cheng B, Lu Y, et al. Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes. 2010;59:2043–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  63. D’Agati V, Yan SF, Ramasamy R, Schmidt AM. RAGE, glomerulosclerosis and proteinuria: roles in podocytes and endothelial cells. Trends Endocrinol Metab. 2010;21:50–6.

    PubMed  Google Scholar 

  64. D’Agati V, Schmidt AM. RAGE and the pathogenesis of chronic kidney disease. Nat Rev Nephrol. 2010;6:352–60.

    PubMed  Google Scholar 

  65. Cottone S, Lorito MC, Riccobene R, Nardi E, Mule G, Buscemi S, et al. Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J Nephrol. 2008;21:175–9.

    PubMed  Google Scholar 

  66. Nakashima A, Carrero JJ, Qureshi AR, Miyamoto T, Anderstam B, Barany P, et al. Effect of circulating soluble receptor for advanced glycation end products (sRAGE) and the proinflammatory RAGE ligand (EN-RAGE, S100A12) on mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2010;5:2213–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Kalousova M, Jachymova M, Mestek O, Hodkova M, Kazderova M, Tesar V, et al. Receptor for advanced glycation end products–soluble form and gene polymorphisms in chronic haemodialysis patients. Nephrol Dial Transplant. 2007;22:2020–6.

    CAS  PubMed  Google Scholar 

  68. Forbes JM, Thorpe SR, Thallas-Bonke V, Pete J, Thomas MC, Deemer ER, 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;16:2363–72.

    CAS  PubMed  Google Scholar 

  69. Leonardis D, Basta G, Mallamaci F, Cutrupi S, Pizzini P, Tripepi R, et al. Circulating soluble receptor for advanced glycation end product (sRAGE) and left ventricular hypertrophy in patients with chronic kidney disease (CKD). Nutr Metab Cardiovasc Dis. 2012;22:748–55.

    CAS  PubMed  Google Scholar 

  70. Yan SF, Ramasamy R, Schmidt AM. Soluble RAGE: therapy and biomarker in unraveling the RAGE axis in chronic disease and aging. Biochem Pharmacol. 2010;79:1379–86.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Raposeiras-Roubin S, Rodino-Janeiro BK, Grigorian-Shamagian L, Moure-Gonzalez M, Seoane-Blanco A, Varela-Roman A, et al. Soluble receptor of advanced glycation end products levels are related to ischaemic aetiology and extent of coronary disease in chronic heart failure patients, independent of advanced glycation end products levels: New Roles for Soluble RAGE. Eur J Heart Fail. 2010;12:1092–100.

    CAS  PubMed  Google Scholar 

  72. Vazzana N, Santilli F, Cuccurullo C, Davi G. Soluble forms of RAGE in internal medicine. Intern Emerg Med. 2009;4:389–401.

    PubMed  Google Scholar 

  73. Sung JY, Chung W, Kim AJ, Kim HS, Ro H, Chang JH, et al. Calcitriol treatment increases serum levels of the soluble receptor of advanced glycation end products in hemodialysis patients with secondary hyperparathyroidism. Tohoku J Exp Med. 2013;230:59–66.

    CAS  PubMed  Google Scholar 

  74. Zakiyanov O, Kalousova M, Kriha V, Zima T, Tesar V. Serum S100A12 (EN-RAGE) levels in patients with decreased renal function and subclinical chronic inflammatory disease. Kidney Blood Press Res. 2011;34:457–64.

    CAS  PubMed  Google Scholar 

  75. Menini T, Ikeda H, Kimura S, Gugliucci A. Circulating soluble RAGE increase after a cerebrovascular event. Clin Chem Lab Med. 2014;52:109–16.

    CAS  PubMed  Google Scholar 

  76. Mahajan N, Mahmood S, Jain S, Dhawan V. Receptor for advanced glycation end products (RAGE), inflammatory ligand EN-RAGE and soluble RAGE (sRAGE) in subjects with Takayasu’s arteritis. Int J Cardiol. 2013;168:532–4.

    PubMed  Google Scholar 

  77. Fujisawa K, Katakami N, Kaneto H, Naka T, Takahara M, Sakamoto F, et al. Circulating soluble RAGE as a predictive biomarker of cardiovascular event risk in patients with type 2 diabetes. Atherosclerosis. 2013;227:425–8.

    CAS  PubMed  Google Scholar 

  78. Falcone C, Bozzini S, Guasti L, D’Angelo A, Capettini AC, Paganini EM, et al. Soluble RAGE plasma levels in patients with coronary artery disease and peripheral artery disease. ScientificWorldJournal. 2013;2013:584504.

    PubMed Central  PubMed  Google Scholar 

  79. Skrha Jr J, Kalousova M, Svarcova J, Muravska A, Kvasnicka J, Landova L, et al. Relationship of soluble RAGE and RAGE ligands HMGB1 and EN-RAGE to endothelial dysfunction in type 1 and type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2012;120:277–81.

    CAS  PubMed  Google Scholar 

  80. Sourris KC, Morley AL, Koitka A, Samuel P, Coughlan MT, Penfold SA, et al. 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. Diabetologia. 2010;53:2442–51.

    CAS  PubMed  Google Scholar 

  81. Ishibashi Y, Yamagishi S, Matsui T, Ohta K, Tanoue R, Takeuchi M, et al. Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level. Metabolism. 2012;61:1067–72.

    CAS  PubMed  Google Scholar 

  82. Tang SC, Chan LY, Leung JC, Cheng AS, Lin M, Lan HY, et al. Differential effects of advanced glycation end-products on renal tubular cell inflammation. Nephrology (Carlton). 2011;16:417–25.

    CAS  Google Scholar 

  83. Yamagishi S, Nakamura K, Matsui T, Ueda S, Fukami K, Okuda S. Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications. Expert Opin Investig Drugs. 2008;17:983–96.

    CAS  PubMed  Google Scholar 

  84. Gada E, Owens AW, Gore MO, See R, Abdullah SM, Ayers CR, et al. Discordant effects of rosiglitazone on novel inflammatory biomarkers. Am Heart J. 2013;165:609–14.

    CAS  PubMed  Google Scholar 

  85. Lanati N, Emanuele E, Brondino N, Geroldi D. Soluble RAGE-modulating drugs: state-of-the-art and future perspectives for targeting vascular inflammation. Curr Vasc Pharmacol. 2010;8:86–92.

    CAS  PubMed  Google Scholar 

  86. Tan KC, Chow WS, Tso AW, Xu A, Tse HF, Hoo RL, et al. Thiazolidinedione increases serum soluble receptor for advanced glycation end-products in type 2 diabetes. Diabetologia. 2007;50:1819–25.

    CAS  PubMed  Google Scholar 

  87. Daroux M, Prevost G, Maillard-Lefebvre H, Gaxatte C, D’Agati VD, Schmidt AM, et al. Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab. 2010;36:1–10.

    CAS  PubMed  Google Scholar 

  88. Harcourt BE, Sourris KC, Coughlan MT, Walker KZ, Dougherty SL, Andrikopoulos S, et al. Targeted reduction of advanced glycation improves renal function in obesity. Kidney Int. 2011;80:190–8.

    CAS  PubMed  Google Scholar 

  89. Busch M, Franke S, Ruster C, Wolf G. Advanced glycation end-products and the kidney. Eur J Clin Invest. 2010;40:742–55.

    CAS  PubMed  Google Scholar 

  90. Maillard-Lefebvre H, Boulanger E, Daroux M, Gaxatte C, Hudson BI, Lambert M. Soluble receptor for advanced glycation end products: a new biomarker in diagnosis and prognosis of chronic inflammatory diseases. Rheumatology (Oxford). 2009;48:1190–6.

    Google Scholar 

  91. Nishizawa Y, Koyama H. Endogenous secretory receptor for advanced glycation end-products and cardiovascular disease in end-stage renal disease. J Ren Nutr. 2008;18:76–82.

    PubMed  Google Scholar 

  92. Kim JK, Park S, Lee MJ, Song YR, Han SH, Kim SG, et al. Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis. Atherosclerosis. 2012;220:208–14.

    CAS  PubMed  Google Scholar 

  93. Inagi R, Yamamoto Y, Nangaku M, Usuda N, Okamato H, Kurokawa K, et al. A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice. Diabetes. 2006;55:356–66.

    CAS  PubMed  Google Scholar 

  94. Tanaka K, Nakayama M, Kanno M, Kimura H, Watanabe K, Tani Y, et al. Skin autofluorescence is associated with the progression of chronic kidney disease: a prospective observational study. PLoS One. 2013;8:e83799.

    PubMed Central  PubMed  Google Scholar 

  95. Susantitaphong P, Siribamrungwong M, Jaber BL. Convective therapies versus low-flux hemodialysis for chronic kidney failure: a meta-analysis of randomized controlled trials. Nephrol Dial Transplant. 2013;28:2859–74.

    CAS  PubMed  Google Scholar 

  96. Mac-Way F, Couture V, Utescu MS, Ignace S, De Serres SA, Loignon RC, et al. Advanced glycation end products, aortic stiffness, and wave reflection in peritoneal dialysis as compared to hemodialysis. Int Urol Nephrol. 2014;46(4):817–24.

    CAS  PubMed  Google Scholar 

  97. Crowley LE, Johnson CP, McIntyre N, Fluck RJ, McIntyre CW, Taal MW, et al. Tissue advanced glycation end product deposition after kidney transplantation. Nephron Clin Pract. 2013;124:54–9.

    CAS  PubMed  Google Scholar 

  98. Makulska I, Szczepanska M, Drozdz D, Polak-Jonkisz D, Zwolinska D. Skin autofluorescence as a marker of cardiovascular risk in children with chronic kidney disease. Pediatr Nephrol. 2013;28:121–8.

    PubMed Central  PubMed  Google Scholar 

  99. Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes. 2012;61:549–59.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Lunceford N, Gugliucci A. Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea. Fitoterapia. 2005;76:419–27.

    PubMed  Google Scholar 

  101. Gugliucci A, Bastos DH, Schulze J, Souza MF. Caffeic and chlorogenic acids in Ilex paraguariensis extracts are the main inhibitors of AGE generation by methylglyoxal in model proteins. Fitoterapia. 2009;80:339–44.

    CAS  PubMed  Google Scholar 

  102. Gugliucci A, Menini T. The polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules? Life Sci. 2003;72:2603–16.

    CAS  PubMed  Google Scholar 

  103. Gugliucci A, Menini T. The botanical extracts of Achyrocline satureoides and Ilex paraguariensis prevent methylglyoxal-induced inhibition of plasminogen and antithrombin III. Life Sci. 2002;72:279–92.

    CAS  PubMed  Google Scholar 

  104. Sri Harsha PS, Gardana C, Simonetti P, Spigno G, Lavelli V. Characterization of phenolics, in vitro reducing capacity and anti-glycation activity of red grape skins recovered from winemaking by-products. Bioresour Technol. 2013;140:263–8.

    CAS  PubMed  Google Scholar 

  105. Saraswat M, Reddy PY, Muthenna P, Reddy GB. Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications. Br J Nutr. 2009;101:1714–21.

    CAS  PubMed  Google Scholar 

  106. Rasheed Z, Anbazhagan AN, Akhtar N, Ramamurthy S, Voss FR, Haqqi TM. Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes. Arthritis Res Ther. 2009;11:R71.

    PubMed Central  PubMed  Google Scholar 

  107. Babu PV, Sabitha KE, Shyamaladevi CS. Effect of green tea extract on advanced glycation and cross-linking of tail tendon collagen in streptozotocin induced diabetic rats. Food Chem Toxicol. 2008;46:280–5.

    CAS  PubMed  Google Scholar 

  108. Ouyang P, Peng WL, Xu DL, Lai WY, Xu AL. Green tea polyphenols inhibit advanced glycation end product-induced rat vascular smooth muscle cell proliferation. Di Yi Jun Yi Da Xue Xue Bao. 2004;24:247–51.

    CAS  PubMed  Google Scholar 

  109. Engelen L, Stehouwer CD, Schalkwijk CG. Current therapeutic interventions in the glycation pathway: evidence from clinical studies. Diabetes Obes Metab. 2013;15:677–89.

    CAS  PubMed  Google Scholar 

  110. Desai K, Wu L. Methylglyoxal and advanced glycation endproducts: new therapeutic horizons? Recent Pat Cardiovasc Drug Discov. 2007;2:89–99.

    CAS  PubMed  Google Scholar 

  111. Thomas MC, Baynes JW, Thorpe SR, Cooper ME. The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. Curr Drug Targets. 2005;6:453–74.

    CAS  PubMed  Google Scholar 

  112. Susic D. Cross-link breakers as a new therapeutic approach to cardiovascular disease. Biochem Soc Trans. 2007;35:853–6.

    CAS  PubMed  Google Scholar 

  113. Coughlan MT, Forbes JM, Cooper ME. Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes. Kidney Int Suppl. 2007;106:S54–60.

    CAS  PubMed  Google Scholar 

  114. Balakumar P, Rohilla A, Krishan P, Solairaj P, Thangathirupathi A. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010;61:482–8.

    CAS  PubMed  Google Scholar 

  115. Beltramo E, Berrone E, Tarallo S, Porta M. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol. 2008;45:131–41.

    CAS  PubMed  Google Scholar 

  116. Matsui T, Yamagishi S, Takeuchi M, Ueda S, Fukami K, Okuda S. Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression. Pharmacol Res. 2010;61:34–9.

    CAS  PubMed  Google Scholar 

  117. Yamagishi S, Nakamura K, Matsui T, Noda Y, Imaizumi T. Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication. Curr Pharm Des. 2008;14:487–95.

    CAS  PubMed  Google Scholar 

  118. Williams ME. New potential agents in treating diabetic kidney disease: the fourth act. Drugs. 2006;66:2287–98.

    CAS  PubMed  Google Scholar 

  119. Miyata T, van Ypersele de Strihou C, Ueda Y, Ichimori K, Inagi R, Onogi H, et al. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol. 2002;13:2478–87.

    CAS  PubMed  Google Scholar 

  120. Forbes JM, Cooper ME, Thallas V, Burns WC, Thomas MC, Brammar GC, et al. Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy. Diabetes. 2002;51:3274–82.

    CAS  PubMed  Google Scholar 

  121. Ishibashi Y, Nishino Y, Matsui T, Takeuchi M, Yamagishi S. Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level. Metabolism. 2011;60:1271–7.

    CAS  PubMed  Google Scholar 

  122. Lu C, He JC, Cai W, Liu H, Zhu L, Vlassara H. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proc Natl Acad Sci U S A. 2004;101:11767–72.

    CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Glycation, Oxidation and Disease Laboratory, Department of Research, College of Osteopathic Medicine, Touro University-California, 1310 Club Drive, 94592, Vallejo, CA, USA

    Alejandro Gugliucci & Teresita Menini

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  1. Alejandro Gugliucci
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  2. Teresita Menini
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Correspondence to Alejandro Gugliucci .

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  1. Hospital Universitari de Sant Joan, IISPV, URV, Unitat de Recerca Biomèdica, Reus, Spain

    Jordi Camps

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Gugliucci, A., Menini, T. (2014). The Axis AGE-RAGE-Soluble RAGE and Oxidative Stress in Chronic Kidney Disease. In: Camps, J. (eds) Oxidative Stress and Inflammation in Non-communicable Diseases - Molecular Mechanisms and Perspectives in Therapeutics. Advances in Experimental Medicine and Biology, vol 824. Springer, Cham. https://doi.org/10.1007/978-3-319-07320-0_14

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