TY - JOUR
T1 - Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes
AU - Koska, Juraj
AU - Gerstein, Hertzel C.
AU - Beisswenger, Paul J.
AU - Reaven, Peter D.
N1 - Funding Information:
Funding. This study was supported by National Heart, Lung, and Blood Institute, National Institutes of Health, grant R21-HL-150268 (J.K.). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.K. obtained funding and analyzed the data. J.K. and P.D.R. wrote the manuscript. P.J.B. collected the data. All authors contributed to the conception and design of the work, interpretation of the data, reviewed and provided edits and comments on manuscript, approved the final version of the manuscript, and agree to be accountable for all aspects of the work. J.K. and P.D.R. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Part of this study was presented in abstract form as an oral presentation at the American Diabetes Association Virtual Scientific Sessions, 25–29 June 2021.
Publisher Copyright:
© 2022 by the American Diabetes Association.
PY - 2022/3
Y1 - 2022/3
N2 - OBJECTIVE To evaluate the association of a multicomponent advanced glycation end product (AGE) panel with decline in kidney function and its utility in predicting renal function loss (RFL) when added to routine clinical measures in type 2 diabetes. RESEARCH DESIGN AND METHODS Carboxymethyl and carboxyethyl lysine and methylglyoxal, 3-deoxyglucosone, and glyoxal hydroimidazolones were measured in baseline serum and plasma samples, respectively, from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (n = 1,150) and Veterans Affairs Diabetes Trial (VADT) (n = 447) partici-pants. A composite AGE score was calculated from individual AGE z scores. The primary outcome was a sustained 30% decline in estimated glomerular filtration rate (eGFR) (30% RFL in both cohorts). Secondary outcomes (in ACCORD) were 40% RFL, macroalbuminuria, and high-risk chronic kidney disease (hrCKD). RESULTS After adjustment for baseline and follow-up HbA1c and other risk factors in ACCORD, the AGE score was associated with reduction in eGFR (β-estimate-0.66 mL/min .1.73 m2 per year; P = 0.001), 30% RFL (hazard ratio 1.42 [95% CI 1.13–1.78]; P = 0.003), 40% RFL (1.40 [1.13–1.74]; P = 0.003), macroalbuminuria (1.53 [1.13–2.06]; P = 0.006), and hrCKD (1.88 [1.37–2.57]; P < 0.0001). AGE score improved net reclassification (NRI) and relative integrated discrimination (IDI) for 30% RFL (NRI 23%; P = 0.02) (relative IDI 7%; P = 0.009). In VADT, the AGE score calculated by the ACCORD-derived coefficients was associated with 30% RFL (1.37 [1.03–1.82); P = 0.03) and improved NRI (24%; P = 0.03) but not IDI (P = 0.18). CONCLUSIONS These data provide further support for a causal role of AGEs in diabetic nephrop-athy independently of glycemic control and suggest utility of the composite AGE panel in predicting long-term decline in renal function.
AB - OBJECTIVE To evaluate the association of a multicomponent advanced glycation end product (AGE) panel with decline in kidney function and its utility in predicting renal function loss (RFL) when added to routine clinical measures in type 2 diabetes. RESEARCH DESIGN AND METHODS Carboxymethyl and carboxyethyl lysine and methylglyoxal, 3-deoxyglucosone, and glyoxal hydroimidazolones were measured in baseline serum and plasma samples, respectively, from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (n = 1,150) and Veterans Affairs Diabetes Trial (VADT) (n = 447) partici-pants. A composite AGE score was calculated from individual AGE z scores. The primary outcome was a sustained 30% decline in estimated glomerular filtration rate (eGFR) (30% RFL in both cohorts). Secondary outcomes (in ACCORD) were 40% RFL, macroalbuminuria, and high-risk chronic kidney disease (hrCKD). RESULTS After adjustment for baseline and follow-up HbA1c and other risk factors in ACCORD, the AGE score was associated with reduction in eGFR (β-estimate-0.66 mL/min .1.73 m2 per year; P = 0.001), 30% RFL (hazard ratio 1.42 [95% CI 1.13–1.78]; P = 0.003), 40% RFL (1.40 [1.13–1.74]; P = 0.003), macroalbuminuria (1.53 [1.13–2.06]; P = 0.006), and hrCKD (1.88 [1.37–2.57]; P < 0.0001). AGE score improved net reclassification (NRI) and relative integrated discrimination (IDI) for 30% RFL (NRI 23%; P = 0.02) (relative IDI 7%; P = 0.009). In VADT, the AGE score calculated by the ACCORD-derived coefficients was associated with 30% RFL (1.37 [1.03–1.82); P = 0.03) and improved NRI (24%; P = 0.03) but not IDI (P = 0.18). CONCLUSIONS These data provide further support for a causal role of AGEs in diabetic nephrop-athy independently of glycemic control and suggest utility of the composite AGE panel in predicting long-term decline in renal function.
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U2 - 10.2337/dc21-2196
DO - 10.2337/dc21-2196
M3 - Article
C2 - 35051276
AN - SCOPUS:85125883948
SN - 1935-5548
VL - 45
SP - 684
EP - 691
JO - Diabetes Care
JF - Diabetes Care
IS - 3
ER -