Zee Jarcy, Muenz Daniel, McCullough Keith P, Bieber Brian, Metzger Marie, Alencar de Pinho Natalia, Lopes Antonio A, Fliser Danilo, Robinson Bruce M, Young Eric, Pisoni Ronald L, Stengel Bénédicte, Pecoits-Filho Roberto
Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania.
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Kidney Med. 2021 Dec 11;4(2):100395. doi: 10.1016/j.xkme.2021.10.008. eCollection 2022 Feb.
RATIONALE & OBJECTIVE: Potential surrogate end points for kidney failure have been proposed in chronic kidney disease (CKD); however, they must be evaluated to ensure accurate, powerful, and harmonized research, particularly among patients with advanced CKD. The aim of the current study was to investigate the power and predictive ability of surrogate kidney failure end points in a population with moderate-to-advanced CKD.
Analysis of longitudinal data of a large multinational CKD observational study (Chronic Kidney Disease Outcomes and Practice Patterns Study).
SETTING & PARTICIPANTS: CKD stage 3-5 patients from Brazil, France, Germany, and the United States.
Reaching an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m or eGFR decline of ≥40%, and composite end points of these individual end points.
Each end point was used as a time-varying indicator in the Cox model to predict the time to kidney replacement therapy (KRT; dialysis or transplant) and was compared by the number of events and prediction accuracy.
8,211 patients had a median baseline eGFR of 27 mL/min/1.73 m (interquartile range, 21-36 mL/min/1.73 m) and 1,448 KRT events over a median follow-up of 2.7 years (interquartile range, 1.2-3.0 years). Among CKD stage 4 patients, the eGFR < 15 mL/min/1.73 m end point had higher prognostic ability than 40% eGFR decline, but the end points were similar for CKD stage 3 patients. The combination of eGFR < 15 mL/min/1.73 m and 40% eGFR decline had the highest prognostic ability for predicting KRT, regardless of the CKD stage. Including KRT in the composite can increase the number of events and, therefore, the power.
Variable visit frequency resulted in variable eGFR measurement frequency.
The composite end point can be useful for CKD progression studies among patients with advanced CKD. Harmonized use of this approach has the potential to accelerate the translation of new discoveries to clinical practice by identifying risk factors and treatments for kidney failure.
慢性肾脏病（CKD）中已提出了肾衰竭的潜在替代终点；然而，必须对其进行评估，以确保研究准确、有力且协调一致，尤其是在晚期CKD患者中。本研究的目的是调查中度至重度CKD人群中替代肾衰竭终点的效力和预测能力。
对一项大型跨国CKD观察性研究（慢性肾脏病预后和实践模式研究）的纵向数据进行分析。
来自巴西、法国、德国和美国的CKD 3-5期患者。
估计肾小球滤过率（eGFR）<15 mL/min/1.73 m²或eGFR下降≥40%，以及这些个体终点的复合终点。
在Cox模型中，将每个终点用作时变指标，以预测开始肾脏替代治疗（KRT；透析或移植）的时间，并通过事件数量和预测准确性进行比较。
8211例患者的基线eGFR中位数为27 mL/min/1.73 m²（四分位间距，21-36 mL/min/1.73 m²），在中位随访2.7年（四分位间距，1.2-3.0年）期间发生1448例KRT事件。在CKD 4期患者中，eGFR<15 mL/min/1.73 m²终点的预后能力高于eGFR下降40%，但在CKD 3期患者中，这两个终点相似。无论CKD分期如何，eGFR<15 mL/min/1.73 m²和eGFR下降40%的组合对预测KRT具有最高的预后能力。将KRT纳入复合终点可增加事件数量，从而提高效力。
就诊频率不一导致eGFR测量频率各异。
复合终点对晚期CKD患者的CKD进展研究可能有用。统一使用这种方法有可能通过识别肾衰竭的危险因素和治疗方法，加速新发现向临床实践的转化。
