Volume 76, Pages S3-S11 (December 2009) Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging  Helen Vlassara, Massimo Torreggiani, James B. Post, Feng Zheng, Jaime Uribarri, Gary E. Striker  Kidney International  Volume 76, Pages S3-S11 (December 2009) DOI: 10.1038/ki.2009.401 Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 1 Survival curves in patients stratified by measured or estimated creatinine clearance. Upper panels reprinted from Pizzarelli et al.9 by permission of Oxford University Press on behalf of the European Renal Association-European Dialysis and Transplant Association. CrCl, creatinine clearance; MDRD, Modification of Diet in Renal Disease equation. Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 2 Key opposing roles of two major AGE receptors. AGE, advanced glycation end product; AGER1, AGE receptor-1; RAGE, receptor for AGE. Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 3 Age-related changes in serum AGE levels and renal function in a cohort of normal subjects. (a and b) Serum levels of CML and MG correlate with age. (c) Serum CML levels inversely correlate with the estimated glomerular filtration rate in the overall study cohort. (c, inset) A subgroup exists within the study cohort who do not show an age-related renal decline. CML, carboxymethyllysine; eGFRCr, estimated glomerular filtration rate using creatinine; MG, methylglyoxal. Reprinted with permission of the American Society of Nephrology from Vlassara et al., Chapter 7, Online Geriatric Nephrology Curriculum, 2009 (http://www.asn-online.org/education_and_meetings/geriatrics). Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 4 Effects of AGEs on inflammation in healthy subjects. (a) Serum AGEs correlate with plasma lipid peroxidation products (8-isoprostanes) in nondiabetic subjects. (b) Levels of hsCRP and TNF-α are elevated in healthy subjects consuming AGE-rich diets (>23 Eq/day) but not in those consuming a low-AGE diet (<15.4 Eq/day). Note that the high-AGE group had a body mass index >33. *P=0.025. AGE, advanced glycation end product; hsCRP, high-sensitivity C-reactive protein; sAGE, serum AGE; TNF-α, tumor necrosis factor-α. Reprinted with permission of the American Society of Nephrology from Vlassara et al., Chapter 7, Online Geriatric Nephrology Curriculum, 2009 (http://www.asn-online.org/education_and_meetings/geriatrics). Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 5 Alterations in markers of oxidant stress and inflammation resulting from reducing the amounts of AGEs in the diet of normal subjects and CKD patients. In both groups (a and b), subjects continued their normal diet but prepared their food using cooking methods specifically designed to reduce dietary AGE content by ∼50%. AGE, advanced glycation end product; AGER1, AGE receptor-1; CKD, chronic kidney disease; 8-iso, 8-isoprostane; RAGE, receptor for AGE; sCML, serum carboxymethyllysine. Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 6 Serum and urine AGE kinetics in normal or diabetic subjects. (a) Normal adults were fed a regular (i.e., high-AGE, solid lines) meal or a meal with 50% lower AGEs (i.e., low-AGE, dashed lines). (b) Diabetic patients with very little (dashed lines) or mild nephropathy (solid lines) were fed the regular (i.e., high-AGE) meal. Compared with normal subjects, the diabetic group with a lower glomerular filtration rate had higher baseline and more prolonged elevation of serum AGE levels, corresponding to significantly reduce urine AGE levels. Note that although neither diabetic group had severe disease, both had markedly lower AGE excretion than normal subjects. AGE, advanced glycation end product; μ/alb, microalbuminuria; CCr, creatinine clearance. Reprinted with permission of the American Society of Nephrology from Vlassara et al., Chapter 7, Online Geriatric Nephrology Curriculum, 2009 (http://www.asn-online.org/education_and_meetings/geriatrics). Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions

Figure 7 Cardiac and renal fibrosis as a direct result of the amount of AGEs in the diet. Kidney (a–c) and cardiac (d–f) histology in healthy mice fed an ad-lib (high-AGE), a calorie-restricted (40–50% reduction), or an MG-supplemented calorie-restricted diet. Kidney and heart lesions were less severe in calorie-restricted mice than in those fed either the ad-lib diet or the calorie-restricted diet supplemented with MG. AGE, advanced glycation end product; CR, calorie restricted; MG, methylglyoxal. Original magnification × 250. Reprinted from Cai et al.12 with permission from the American Society for Investigative Pathology. Kidney International 2009 76, S3-S11DOI: (10.1038/ki.2009.401) Copyright © 2009 International Society of Nephrology Terms and Conditions