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) participants. 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 nephropathy independently of glycemic control and suggest utility of the composite AGE panel in predicting long-term decline in renal function.

中文翻译：

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晚期糖基化终产物预测 2 型糖尿病患者的肾功能丧失和高危慢性肾脏病。

目的 评估多组分晚期糖基化终末产物 (AGE) 组与肾功能下降的关联，以及将其添加到 2 型糖尿病常规临床测量中预测肾功能丧失 (RFL) 的效用。研究设计和方法 羧甲基和羧乙基赖氨酸和甲基乙二醛、3-脱氧葡萄糖酮和乙二醛氢咪唑酮分别在控制糖尿病心血管风险行动 (ACCORD) (n = 1,150) 和退伍军人事务糖尿病试验的基线血清和血浆样本中进行测量(VADT) (n = 447) 参与者。根据个人 AGE z 分数计算综合 AGE 分数。主要结果是估计肾小球滤过率 (eGFR) 持续下降 30%（两个队列的 RFL 均为 30%）。次要结果（在 ACCORD 中）是 40% RFL、大量白蛋白尿、和高危慢性肾脏病（hrCKD）。结果 在 ACCORD 中调整基线和随访 HbA1c 和其他危险因素后，AGE 评分与 eGFR 降低相关（β-估计 -0.66 mL/min ⋅ 1.73 m2 每年；P = 0.001），30% RFL（风险比 1.42 [95% CI 1.13-1.78]；P = 0.003）、40% RFL（1.40 [1.13-1.74]；P = 0.003）、大量白蛋白尿（1.53 [1.13-2.06]；P = 0.006）和 hrCKD（ 1.88 [1.37-2.57]；P < 0.0001）。对于 30% RFL（NRI 23%；P = 0.02）（相对 IDI 7%；P = 0.009），AGE 评分改善了净重新分类 (NRI) 和相对综合歧视 (IDI)。在 VADT 中，由 ACCORD 衍生系数计算的 AGE 评分与 30% RFL (1.37 [1.03-1.82) 相关；P = 0.03) 和改善的 NRI (24%; P = 0.03) 但不是 IDI (P = 0.18)。