Increasing evidence in the literature suggests an important role for advanced glycation end products (AGEs) in the generation of a state of increased oxidative stress and chronic subclinical inflammation, which underlies most modern chronic diseases, including diabetes, cardiovascular disease and chronic kidney disease (CKD). Although AGEs were originally thought to form only endogenously, primarily as the result of the hyperglycemia of diabetes, it is now clear that exogenous AGEs, specially incorporated in foods, are an important contributor to the body pool of AGEs. Over the past decade, several clinical trials have been performed in a variety of conditions demonstrating that the application of an AGE-restricted diet reduces not only the systemic levels of AGEs but also the levels of markers of oxidative stress and inflammation. This has been shown in CKD patients before and after the initiation of dialysis and either in the presence or absence of coexistent diabetes. Reduction of the AGE content in food is obtained by simple changes in culinary techniques and appears to be a feasible, easily applicable and safe intervention, even in advanced CKD patients.

1.
Gugliucci A, Menini T: The axis AGE-RAGE-soluble RAGE and oxidative stress in chronic kidney disease. Adv Exp Med Biol 2014;824:191-208.
2.
Chilelli NC, Burlina S, Lapolla A: AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a ‘glycoxidation-centric' point of view. Nutr Metab Cardiovasc Dis 2013;23:913-919.
3.
Uribarri J, Cai W, Peppa M, Goodman S, Ferrucci L, Striker G, Vlassara H: Circulating glycotoxins and dietary advanced glycation endproducts: two links to inflammatory response, oxidative stress, and aging. J Gerontol A Biol Sci Med Sci 2007;62:427-433.
4.
Vlassara H, Uribarri J: Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Curr Diab Rep 2014;14:453.
5.
Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M, Rayfield EJ: Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci U S A 2002;99:15596-15601.
6.
Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, He C, Vlassara H: Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol 2003;14:728-731.
7.
Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J: Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE-receptor-1. J Clin Endocrinol Metab 2009;94:4483-4491.
8.
Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H: Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care 2011;34:1610-1616.
9.
Birlouez-Aragon I, Saavedra G, Tessier FJ, Galinier A, Ait-Ameur L, Lacoste F, Niamba CN, Alt N, Somoza V, Lecerf JM: A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases. Am J Clin Nutr 2010;91:1220-1226.
10.
Luévano-Contreras C, Garay-Sevilla ME, Wrobel K, Malacara JM, Wrobel K: Dietary advanced glycation end products restriction diminishes inflammation markers and oxidative stress in patients with type 2 diabetes mellitus. J Clin Biochem Nutr 2013;52:22-26.
11.
Peppa M, Uribarri J, Cai W, Lu M, Vlassara H: Glycoxidation and inflammation in renal failure patients. Am J Kidney Dis 2004;43:690-695.
12.
Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H: Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 2004;104:1287-1291.
13.
Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H: Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 2010;110:911-916.e12.
14.
Monden M, Koyama H, Otsuka Y, Morioka T, Mori K, Shoji T, Mima Y, Motoyama K, Fukumoto S, Shioi A, Emoto M, Yamamoto Y, Yamamoto H, Nishizawa Y, Kurajoh M, Yamamoto T, Inaba M: Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2. Diabetes 2013;62:478-489.
15.
Cai W, Ramdas M, Zhu L, Chen X, Striker GE, Vlassara H: Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc Natl Acad Sci U S A 2012;109:15888-15893.
16.
Vlassara H, Uribarri J, Cai W, Striker G: Advanced glycation end product homeostasis: exogenous oxidants and innate defenses. Ann N Y Acad Sci 2008;1126:46-52.
17.
Linden E, Cai W, He JC, Xue C, Li Z, Winston J, Vlassara H, Uribarri J: 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;3:691-698.
18.
Wagner Z, Molnár M, Molnár GA, Tamaskó M, Laczy B, Wagner L, Csiky B, Heidland A, Nagy J, Wittmann I: Serum carboxymethyllysine predicts mortality in hemodialysis patients. Am J Kidney Dis 2006;47:294-300.
19.
Meerwaldt R, Hartog JW, Graaff R, Huisman RJ, Links TP, den Hollander NC, Thorpe SR, Baynes JW, Navis G, Gans RO, Smit AJ: Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol 2005;16:3687-3693.
20.
Schwedler SB, Metzger T, Schinzel R, Wanner C: Advanced glycation end products and mortality in hemodialysis patients. Kidney Int 2002;62:301-310.
21.
Fagugli RM, Vanholder R, De Smet R, Selvi A, Antolini F, Lameire N, Floridi A, Buoncristiani U: Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis. Int J Artif Organs 2001;24:256-262.
22.
Gerdemann A, Wagner Z, Solf A, Bahner U, Heidland A, Vienken J, Schinzel R: Plasma levels of advanced glycation end products during haemodialysis, haemodiafiltration and haemofiltration: potential importance of dialysate quality. Nephrol Dial Transplant 2002;17:1045-1049.
23.
Lin CL, Huang CC, Yu CC, Yang HY, Chuang FR, Yang CW: Reduction of advanced glycation end product levels by on-line hemodiafiltration in long-term hemodialysis patients. Am J Kidney Dis 2003;42:524-531.
24.
Friedlander MA, Wu YC, Schulak JA, Monnier VM, Hricik DE: Influence of dialysis modality on plasma and tissue concentrations of pentosidine in patients with end-stage renal disease. Am J Kidney Dis 1995;25:445-451.
25.
Slowik-Zylka D, Safranow K, Dziedziejko V, Ciechanowski K, Chlubek D: Association of plasma pentosidine concentrations with renal function in kidney graft recipients. Clin Transplant 2010;24:839-847.
26.
Uribarri J, Tuttle KR: Advanced glycation end products and nephrotoxicity of high-protein diets. Clin J Am Soc Nephrol 2006;1:1293-1299.
27.
Daroux M, Prévost G, Maillard-Lefebvre H, Gaxatte C, D'Agati VD, Schmidt AM, Boulanger E: Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab 2010;36:1-10.
28.
Chuang PY, Yu Q, Fang W, Uribarri J, He JC: Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor. Kidney Int 2007;72:965-976.
29.
Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, Watanabe T, Yamagishi S, Sakurai S, Takasawa S, Okamoto H, Yamamoto H: Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice. J Clin Invest 2001;108:261-268.
30.
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: RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 2003;162:1123-1137.
31.
Soulis T, Cooper ME, Sastra S, Thallas V, Panagiotopoulos S, Bjerrum OJ, Jerums G: Relative contributions of advanced glycation and nitric oxide synthase inhibition to aminoguanidine-mediated renoprotection in diabetic rats. Diabetologia 1997;40:1141-1151.
32.
Peppa M, Brem H, Cai W, Zhang JG, Basgen J, Li Z, Vlassara H, Uribarri J: Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711). Am J Nephrol 2006;26:430-436.
33.
Zheng F, He C, Cai W, Hattori M, Steffes M, Vlassara H: Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products. Diabetes Metab Res Rev 2002;18:224-237.
34.
Uribarri J, Cai W, Pyzik R, Goodman S, Chen X, Zhu L, Ramdas M, Striker GE, Vlassara H: Suppression of native defense mechanisms, SIRT1 and PPARγ, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases. Amino Acids 2014;46:301-309.
35.
Vlassara H, Uribarri J, Cai W, Goodman S, Pyzik R, Post J, Grosjean F, Woodward M, Striker GE: Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol 2012;7:934-942.
36.
Yubero-Serrano EM, Woodward M, Poretsky L, Vlassara H, Striker GE: Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. Clin J Am Soc Nephrol 2015, Epub ahead of print.
37.
Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D: Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care 2006;29:2064-2071.
38.
Negrean M, Stirban A, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D: 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.
39.
Nagai R, Shirakawa J, Ohno R, Moroishi N, Nagai M: Inhibition of AGEs formation by natural products. Amino Acids 2014;46:261-266.
40.
Cerami C, Founds H, Nicholl I, Mitsuhashi T, Giordano D, Vanpatten S, Lee A, Al-Abed Y, Vlassara H, Bucala R, Cerami A: Tobacco smoke is a source of toxic reactive glycation products. Proc Natl Acad Sci U S A 1997;94:13915-13920.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.