Ferguson Thomas W, Komenda Paul, Tangri Navdeep
aDepartment of Medicine, Section of Nephrology, Faculty of Health Sciences, University of Manitoba bChronic Disease Innovation Centre, Seven Oaks Hospital Winnipeg, Manitoba, Canada.
Curr Opin Nephrol Hypertens. 2016 May;25(3):240-4. doi: 10.1097/MNH.0000000000000210.
Estimated glomerular filtration rate (eGFR) is important in the diagnosis and prognostication of chronic kidney disease (CKD). The current standards for CKD progression in clinical trials are kidney failure and the doubling of serum creatinine (∼57% decline in eGFR). These endpoints have limitations as they are only applicable to patients with later stages of CKD and often require large sample sizes to achieve adequate power.
Lesser declines in eGFR (30% and 40%) have been evaluated as potential endpoints in recent studies. These endpoints are more common and show a strong association with the risk of end-stage renal disease and mortality. These findings have been shown to be consistent across different causes of CKD and for different interventions. A particular limitation of reduced thresholds is an elevated risk of type I errors in the presence of acute treatment effects, particularly with a 30% eGFR decline cut off.
Surrogate endpoints for kidney failure and mortality are needed in clinical trials to allow for the reasonable management of timelines and resources, and the achievement of adequate sample sizes. Lesser eGFR decline thresholds should be considered to aid in the design and conduct of more randomized controlled trials in nephrology.
估计肾小球滤过率（eGFR）在慢性肾脏病（CKD）的诊断和预后评估中具有重要意义。目前临床试验中CKD进展的标准是肾衰竭和血清肌酐翻倍（eGFR下降约57%）。这些终点存在局限性，因为它们仅适用于CKD晚期患者，并且通常需要大样本量才能获得足够的检验效能。
在最近的研究中，eGFR较小幅度的下降（30%和40%）已被评估为潜在终点。这些终点更为常见，并且与终末期肾病风险和死亡率密切相关。这些发现已被证明在不同病因的CKD以及不同干预措施中具有一致性。降低阈值的一个特别局限性是在存在急性治疗效应时I型错误风险升高，尤其是eGFR下降30%的截断值。
临床试验中需要肾衰竭和死亡率的替代终点，以便合理管理时间和资源，并获得足够的样本量。应考虑较低的eGFR下降阈值，以帮助设计和开展更多肾脏病领域的随机对照试验。
