OBJECTIVE Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers. RESEARCH DESIGN AND METHODS The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 m2/year) for the 7,482 participants with a recorded baseline and follow-up eGFR. Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated. RESULTS During 6.2 years of median follow-up, the median annual change in eGFR was -0.18 mL/min/1.73 m2/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m2 predicted annual fall in eGFR predicted a 13% (95% CI 12, 14%) higher mortality. CONCLUSIONS Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.

中文翻译：

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血糖异常患者肾脏功能变化的新型生物标志物。

目的糖尿病是肾功能下降和衰竭的主要危险因素。生化标志物多重面板的可用性提供了鉴定比常规可用临床标志物更好地预测肾功能变化的新型生物标志物的机会。研究设计与方法在初始甘精胰岛素干预（ORIGIN）试验的生物标志物亚类研究参与者的储藏血清中测量了239种生化标志物的浓度。重复测量的混合效应模型用于计算7,482名参与者的eGFR的年度变化（以mL / min / 1.73 m2 /年衡量），并记录了基线和随访eGFR。在考虑基线HbA1c，基线eGFR和常规测量的临床危险因素后，使用正向选择的线性回归模型来确定eGFR年度变化的独立生物标志物决定因素。从这些模型预测的eGFR变化的每四分之一内，也估计了复合肾结局（即肾替代疗法，肾死亡，肾衰竭，白蛋白尿进展，血清肌酐加倍）的发生率和死亡。结果在6.2年的中位随访期间，eGFR的中位年变化为-0.18 mL / min / 1.73 m2 /年。在考虑到心血管危险因素后，有15种生物标志物独立预测了eGFR下降，在考虑了肾脏危险因素后，其中的12种加上1种其他生物标志物也是如此。每0.1 mL / min / 1。73平方米的预计eGFR的年度下降预测死亡率会增加13％（95％CI 12、14％）。结论在常规测量的临床危险因素中添加多达16种生物标志物可以改善血糖异常患者eGFR年度变化的预测。