Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Fremantle, Western Australia, Australia.
Proteomics International, Perth, Western Australia, Australia.
Diabetes Care. 2017 Nov;40(11):1548-1555. doi: 10.2337/dc17-0911. Epub 2017 Aug 29.
To assess the ability of plasma apolipoprotein (apo) A-IV (apoA4), apo C-III, CD5 antigen-like (CD5L), complement C1q subcomponent subunit B (C1QB), complement factor H-related protein 2, and insulin-like growth factor binding protein 3 (IBP3) to predict rapid decline in estimated glomerular filtration rate (eGFR) in type 2 diabetes.
Mass spectrometry was used to measure baseline biomarkers in 345 community-based patients (mean age 67.0 years, 51.9% males) from the Fremantle Diabetes Study Phase II (FDS2). Multiple logistic regression was used to determine clinical predictors of rapid eGFR decline trajectory defined by semiparametric group-based modeling over a 4-year follow-up period. The incremental benefit of each biomarker was then assessed. Similar analyses were performed for a ≥30% eGFR fall, incident chronic kidney disease (eGFR <60 mL/min/1.73 m), and eGFR decline of ≥5 mL/min/1.73 m/year.
Based on eGFR trajectory analysis, 35 participants (10.1%) were defined as "rapid decliners" (mean decrease 2.9 mL/min/1.73 m/year). After adjustment for clinical predictors, apoA4, CD5L, and C1QB independently predicted rapid decline (odds ratio 2.40 [95% CI 1.24-4.61], 0.52 [0.29-0.93], and 2.41 [1.14-5.11], respectively) and improved model performance and fit ( < 0.001), discrimination (area under the curve 0.75-0.82, 0.039), and reclassification (net reclassification index 0.76 [0.63-0.89]; integrated discrimination improvement 6.3% [2.1-10.4%]). These biomarkers and IBP3 contributed to improved model performance in predicting other indices of rapid eGFR decline.
The current study has identified novel plasma biomarkers (apoA4, CD5L, C1QB, and IBP3) that may improve the prediction of rapid decline in renal function independently of recognized clinical risk factors in type 2 diabetes.
评估血浆载脂蛋白（apo）A-IV（apoA4）、apo C-III、CD5 抗原样（CD5L）、补体 C1q 亚成分亚基 B（C1QB）、补体因子 H 相关蛋白 2 和胰岛素样生长因子结合蛋白 3（IBP3）预测 2 型糖尿病患者估算肾小球滤过率（eGFR）快速下降的能力。
使用质谱法测量来自弗里曼特尔糖尿病研究二期（FDS2）的 345 名社区患者（平均年龄 67.0 岁，51.9%为男性）的基线生物标志物。使用多变量逻辑回归确定快速 eGFR 下降轨迹的临床预测因素，该轨迹由 4 年随访期间的半参数基于群组的建模定义。然后评估每个生物标志物的额外益处。对 eGFR 下降≥30%、新发慢性肾脏病（eGFR<60mL/min/1.73m）和 eGFR 下降≥5mL/min/1.73m/年进行了类似的分析。
基于 eGFR 轨迹分析，35 名参与者（10.1%）被定义为“快速下降者”（平均下降 2.9mL/min/1.73m/年）。调整临床预测因素后，apoA4、CD5L 和 C1QB 可独立预测快速下降（比值比 2.40[95%CI 1.24-4.61]、0.52[0.29-0.93]和 2.41[1.14-5.11]），并改善模型性能和拟合（<0.001）、区分度（曲线下面积 0.75-0.82，0.039）和重新分类（净重新分类指数 0.76[0.63-0.89]；综合区分度改善 6.3%[2.1-10.4%]）。这些生物标志物和 IBP3 有助于改善预测其他快速 eGFR 下降指标的模型性能。
本研究发现了新型血浆生物标志物（apoA4、CD5L、C1QB 和 IBP3），它们可能在 2 型糖尿病中独立于公认的临床危险因素改善肾功能快速下降的预测。
