Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA.
Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA.
Diabetes Care. 2018 Nov;41(11):2361-2369. doi: 10.2337/dc18-0699. Epub 2018 Aug 27.
We examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD).
Using targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD ( = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses.
At baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29-0.87]) and death (HR [95% CI] 0.56 [0.34-0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41-0.79] and 0.66 [0.44-0.97], respectively); higher urine factor H-related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05-2.48]) in fully adjusted models.
In a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.
我们研究了尿补体蛋白与 2 型糖尿病合并蛋白尿性糖尿病肾病（DKD）患者进展为终末期肾病（ESRD）或死亡的关系。
我们使用靶向质谱法对一个以墨西哥裔美国人为主的 2 型糖尿病和蛋白尿性 DKD 患者队列（n=141）的尿液中 12 种补体蛋白的丰度进行了定量分析。使用生存时间分析评估尿补体蛋白与进展为 ESRD 或死亡的关系。
基线时，估计肾小球滤过率（eGFR）中位数为 54 mL/min/1.73 m，尿蛋白/肌酐比为 2.6 g/g。67 名参与者发展为 ESRD 或死亡，其中 39 名在中位数为 3.1 年时进展为 ESRD，40 名在中位数为 3.6 年时死亡。尿 CD59 水平较高（终末补体复合物形成的抑制剂）与 ESRD 风险降低相关（风险比[HR]（每加倍的 95%置信区间）0.50[0.29-0.87]）和死亡风险降低相关（HR[95%CI]0.56[0.34-0.93]），调整人口统计学和临床协变量后，包括基线 eGFR 和蛋白尿。尿液补体成分 4 和 8 水平较高与死亡风险降低相关（HR[95%CI]0.57[0.41-0.79]和 0.66[0.44-0.97]）；尿液因子 H 相关蛋白 2 水平较高（替代补体途径的正调节剂）与全调整模型中死亡风险增加相关（HR[95%CI]1.61[1.05-2.48]）。
在一个以墨西哥裔美国人为主的 2 型糖尿病和蛋白尿性 DKD 患者队列中，几种补体和补体调节蛋白的尿液丰度与进展为 ESRD 和死亡密切相关。
