医学
蛋白尿
肾小球疾病
四分位间距
肾功能
生物标志物
内科学
胃肠病学
肌酐
肾脏疾病
泌尿科
补体因子I
活检
肾
病理
补体系统
免疫学
抗体
化学
生物化学
作者
Steven D. Podos,Howard Trachtman,Gerald B. Appel,Andrew S. Bomback,Bradley P. Dixon,Jack F.M. Wetzels,Terry Cook,Samir Parikh,Matthew C. Pickering,James Tumlin,Craig B. Langman,Liz Lightstone,C. John Sperati,Erica Daina,Koenraad Peter Bouman,Kara Rice,Jane A. Thanassi,Mingjun Huang,Carla M. Nester,Giuseppe Remuzzi
出处
期刊:American Journal of Nephrology
[S. Karger AG]
日期:2022-01-01
卷期号:53 (10): 675-686
被引量:1
摘要
C3 glomerulopathy (C3G) is a rare, progressive kidney disease resulting from dysregulation of the alternative pathway (AP) of complement. Biomarkers at baseline were investigated in patients with C3G who participated in two phase 2 studies with the factor D (FD) inhibitor, danicopan.Patients with biopsy-confirmed C3G, proteinuria ≥500 mg/day, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 were enrolled into two studies (NCT03369236 and NCT03459443). Biomarker analysis was performed for patients with C3G confirmed by central pathology laboratory re-evaluation. Complement and clinical biomarkers, biopsy composite score, and activity and chronicity indices were assessed at baseline and analyzed by pairwise Spearman correlation analysis.Twenty-nine patients were included in the analysis (median [interquartile range] age: 24.0 [10.0] years). Systemic complement AP activation was evident by reduced median concentrations of C3 and C5, elevated sC5b-9, and normal C4, relative to reference ranges. C3 showed strong pairwise correlations with C5 and sC5b-9 (r = 0.80 and -0.73, respectively; p < 0.0001). Baseline Ba and FD concentrations were inversely correlated with eGFR (r = -0.83 and -0.87, respectively; p < 0.0001). Urinary concentrations of sC5b-9 were correlated with both plasma sC5b-9 and proteinuria (r = 0.69 and r = 0.83, respectively; p < 0.0001). Biopsy activity indices correlated strongly with biomarkers of systemic AP activation, including C3 (r = -0.76, p < 0.0001), whereas chronicity indices aligned more closely with eGFR (r = -0.57, p = 0.0021).Associations among complement biomarkers, kidney function, and kidney histology may add to the current understanding of C3G and assist with the characterization of patients with this heterogenous disease.
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