Lorenz Georg, Hettwer Stefan, McCallum Wendy, Angermann Susanne, Wen Ming, Schmaderer Christoph, Heemann Uwe, Roos Marcel, Renders Lutz, Steubl Dominik
Technische Universität München, Fakultät für Medizin, Klinikum rechts der Isar, Abteilung für Nephrologie, Munich, Germany.
Neurotune AG, Schlieren-Zurich, Switzerland.
Medicine (Baltimore). 2019 May;98(19):e15597. doi: 10.1097/MD.0000000000015597.
C-terminal agrin fragment (tCAF) is a promising biomarker for glomerular filtration. Data regarding biomarkers that have the ability to predict rapid progression of chronic kidney disease (CKD) are sparse but necessary in order to identify patients at high risk for rapid progression. This study addresses the value of tCAF as a predictor of rapid kidney function decline in CKD patients.We measured plasma tCAF in a retrospective observational cohort study of 277 prevalent CKD patients stage I-V. Using multivariable Cox proportional hazards regression analysis, we evaluated the association of tCAF with end-stage-renal-disease (ESRD), ≥30%-decline of estimated glomerular filtration rate (eGFR) and the composite endpoint of both, adjusting for eGFR, age, systolic blood pressure, proteinuria and diabetes.The median age was 58 [interquartile range 47, 71] years, 36% were female. Median tCAF level was 822 [594, 1232] pM, eGFR was 32 [19, 48] ml/min/1.73 m. tCAF was correlated to eGFR and proteinuria (r = -0.76 and r = 0.49, P < .001 resp.). During a follow-up of 57.1 [42.9, 71.9] weeks, 36 (13%) patients developed ESRD and 13 (5%) had an eGFR decline of ≥30% (composite endpoint: 49 (18%)). In multivariable analysis, each 100 pM higher tCAF was independently associated with ESRD (hazard ratio (HR) 1.05 (95%-CI 1.02-1.08)), ≥30% eGFR decline (HR 1.10 (1.03-1.18)) and the composite endpoint (HR 1.07 (1.04-1.1)).Plasma tCAF may identify CKD patients at risk for rapid kidney function decline independent of eGFR and other risk factors for eGFR loss such as proteinuria.
C 末端聚集蛋白片段（tCAF）是一种很有前景的肾小球滤过生物标志物。关于能够预测慢性肾脏病（CKD）快速进展的生物标志物的数据稀少，但对于识别快速进展高危患者而言却是必要的。本研究探讨了 tCAF 作为 CKD 患者肾功能快速下降预测指标的价值。我们在一项对 277 例 I - V 期 CKD 现患患者的回顾性观察队列研究中测量了血浆 tCAF。使用多变量 Cox 比例风险回归分析，我们评估了 tCAF 与终末期肾病（ESRD）、估计肾小球滤过率（eGFR）下降≥30%以及两者的复合终点之间的关联，并对 eGFR、年龄、收缩压、蛋白尿和糖尿病进行了校正。中位年龄为 58[四分位间距 47, 71]岁，36%为女性。tCAF 中位水平为 822[594, 1232]pM，eGFR 为 32[19, 48]ml/min/1.73 m²。tCAF 与 eGFR 和蛋白尿相关（r = -0.76 和 r = 0.49，P <.001）。在 57.1[42.9, 71.9]周的随访期间，36 例（13%）患者发生了 ESRD，13 例（5%）患者的 eGFR 下降≥30%（复合终点：49 例（18%））。在多变量分析中，tCAF 每升高 100 pM 分别独立与 ESRD（风险比（HR）1.05（95%置信区间 1.02 - 1.08））、eGFR 下降≥30%（HR 1.10（1.03 - 1.18））以及复合终点（HR 1.07（1.04 - 1.1））相关。血浆 tCAF 可能独立于 eGFR 和其他导致 eGFR 降低的风险因素（如蛋白尿）来识别有肾功能快速下降风险的 CKD 患者。
