187-OR: Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes in the ACCORD Trial Conferences uri icon

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abstract

  • Individual advanced glycation end products (AGEs) have been implicated in the development of chronic kidney disease (CKD). We evaluated the prognostic utility of a comprehensive multicomponent AGE panel in predicting long-term renal function loss and CKD when added to routine clinical measures in persons with type 2 diabetes (T2D) followed for 12.5 years (including risk factor intervention and observation phases). The five key AGEs (carboxymethyl and carboxyethyl lysine, and methylglyoxal, 3-deoxyglucosone and glyoxal hydroimidazolone) were measured via LC-MS/MS in baseline serum from 1,151 the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. A composite AGE score was calculated as the mean of individual AGE z-scores. Outcomes were (1) renal function loss (≥40% decline in estimated glomerular filtration rate [eGFR]), (2) macroalbuminuria (MAU), and (3) high-risk CKD (hrCKD, KDIGO classification). Higher AGE score predicted greater risks of renal function loss (n=260 events, hazard ratio 1.49 [95%CI 1.24-1.79], p<0.0001), MAU (n=96, 1.45 [1.06-1.98], p=0.005) and hrCKD (n=128, 1.95 [1.47-2.57], p<0.0001), independent of baseline eGFR, urine albumin:creatinine, randomization arms, other standard risk factors and hemoglobin A1c. Higher AGE score predicted renal function loss even in those with normal renal function (1.40 [1.06-1.84], p=0.02). When added to routine risk factors, AGE score improved net-reclassification and integrated discrimination for renal function loss (by 19% and 17%, p=0.002) and hrCKD (by 34% and 4.9%; p=0.02), but not MAU (0.8% and 1.3%, p=0.6). There is a strong independent association between AGE burden and progression of CKD in T2D. Adding AGE measures to standard clinical parameters improves the prediction of multiple kidney outcomes, indicating its potential as prognostic biomarker of diabetes nephropathy. Disclosure J. Koska: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. P. J. Beisswenger: Stock/Shareholder; Self; PreventAGE Healthcare LLC. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc. Funding National Institutes of Health (R21HL150268)

publication date

  • June 1, 2021