循环蛋白预测肾脏疾病进展和心血管结局:四个队列的个体参与者数据荟萃分析

IF 3.2 3区 医学 Q1 UROLOGY & NEPHROLOGY
Carolina Lopez-Silva, Aditya Surapaneni, Josef Coresh, Teresa K Chen, Pascal Schlosser, Eugene P Rhee, Sushrut S Waikar, Insa M Schmidt, Rajat Deo, Peter Ganz, Ruth Dubin, Vasan S Ramachandran, Paul L Kimmel, Sarah J Schrauben, Chirag R Parikh, Joseph V Bonventre, Mirela Dobre, Panduranga S Rao, Ana C Ricardo, Matthew R Weir, Morgan E Grams
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引用次数: 0

摘要

背景和目的:KIM-1、TNFRSF1A和TNFRSF1B已被美国食品和药物管理局(fda)认可为糖尿病肾病的早期风险标志物。在其他重要的亚组中,它们是否可以用于识别心血管/肾脏临床试验入组的高危患者尚不确定。方法:我们在四个队列中评估了KIM-1、TNFRSF1A和TNFRSF1B的潜在预后富集:社区动脉粥样硬化风险[ARIC] [N = 4594,平均年龄76岁,55%女性,意味着eGFR 68 mL / min / 1.73平方米)),非裔美国人研究肾病和高血压[AASK] [N = 705,平均年龄55岁,39%女性,意味着mGFR 46 mL / min / 1.73平方米]),慢性肾功能不全组[CRIC] [N = 2943,平均年龄59岁,45%女性,意味着eGFR 35 mL / min / 1.73平方米),和波士顿肾活检组[BKBC] [N = 434,平均年龄54岁,48%女性,意味着eGFR 51 mL / min / 1.73平方米)。我们评估了三个结局:肾小球滤过率(GFR)下降40%、肾衰竭和心血管疾病(CVD)的发生率,以及临床试验中历史上代表性不足的两个亚组:无糖尿病患者和蛋白尿患者。结果:使用临床变量的已发表模型(40%下降工具、肾衰竭风险方程和预防)在每个队列中具有中等至强烈的风险区分:GFR下降40%,AUROC范围:0.78-0.90;肾功能衰竭,c统计值范围:0.75 ~ 0.93;CVD, c -统计范围为0.59 ~ 0.79。在加入生物标志物后,荟萃分析的总体人群有了小而显著的改善:40% GFR下降时AUROC的变化为0.02,结论:KIM-1、TNFRSF1A和TNFRSF1B可能不是超过临床风险估计的强预后富集生物标志物。临床试验应该测试它们是否有助于预测性富集。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts.

Introduction: KIM-1, TNFRSF1A, and TNFRSF1B have been accepted as early risk markers in diabetic kidney disease by the US Food and Drug Administration. Whether they may be useful in identifying high-risk patients for cardiovascular/kidney clinical trial enrollment in other important subgroups is uncertain.

Methods: We evaluated the potential prognostic enrichment of KIM-1, TNFRSF1A, and TNFRSF1B in four cohorts: the Atherosclerosis Risk in Communities (ARIC) (N = 4,594, mean age 76 years, 55% women, mean eGFR 68 mL/min/1.73 m2), African American Study of Kidney Disease and Hypertension (AASK) (N = 705, mean age 55 years, 39% women, mean mGFR 46 mL/min/1.73 m2), Chronic Renal Insufficiency Cohort (CRIC) (N = 2,943, mean age 59 years, 45% women, mean eGFR 35 mL/min/1.73 m2), and Boston Kidney Biopsy Cohort (BKBC) (N = 434, mean age 54 years, 48% women, mean eGFR 51 mL/min/1.73 m2). We evaluated three outcomes: 40% glomerular filtration rate (GFR) decline, kidney failure, and incident cardiovascular disease (CVD) overall and in two subgroups historically underrepresented in clinical trials: participants with no diabetes, and those with albuminuria <200 mg/g.

Results: Published models (40% decline tool, kidney failure risk equation, and PREVENT) using clinical variables had moderate to strong risk discrimination in each cohort: 40% GFR decline, AUROC range: 0.78-0.90; kidney failure, C-statistic range: 0.75-0.93; and CVD, C-statistic range: 0.59-0.79. After addition of biomarkers, there was a small but significant improvement in the meta-analyzed overall population: change in AUROC in 40% GFR decline: 0.02, p < 0.001; change in C-statistic for kidney failure: 0.01, p = 0.02; change in C-statistic for CVD: 0.01, p = 0.03. Among participants without diabetes, the change was statistically significant only for 40% decline; among patient with albuminuria <200 mg/g, the change was statistically significant only for the two kidney outcomes.

Conclusion: KIM-1, TNFRSF1A, and TNFRSF1B may not be strong prognostic enrichment biomarkers over and above clinical risk estimates. Clinical trials should test whether they help with predictive enrichment.

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来源期刊
American Journal of Nephrology
American Journal of Nephrology 医学-泌尿学与肾脏学
CiteScore
7.50
自引率
2.40%
发文量
74
审稿时长
4-8 weeks
期刊介绍: The ''American Journal of Nephrology'' is a peer-reviewed journal that focuses on timely topics in both basic science and clinical research. Papers are divided into several sections, including:
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