Hartung Erum A
Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, 19104, USA.
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA, 19104, USA.
Pediatr Nephrol. 2016 Mar;31(3):381-91. doi: 10.1007/s00467-015-3104-8. Epub 2015 May 16.
Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease.
肾脏疾病及其相关合并症给公共卫生带来了沉重负担。尽管如此，肾脏病学领域的临床试验数量仍落后于许多其他领域。导致肾脏病学试验进展相对缓慢的一个重要因素是现有的临床终点存在重大局限性。慢性肾脏病的“硬”终点，如进展至终末期肾病，可能数十年都无法达到。传统生物标志物，如急性肾损伤中的血清肌酐，可能缺乏敏感性和预测价值。因此，寻找新的生物标志物作为替代终点是肾脏病研究的一个重要优先事项，可能有助于加速肾脏病学临床试验。在本文中，我首先回顾与临床试验终点选择相关的关键概念，并讨论与将生物标志物评估为替代终点相关的统计和监管考虑因素。接下来讨论在肾脏病学研究的三个主要领域——急性肾损伤、慢性肾脏病和常染色体显性多囊肾病——中开发新型生物标志物和替代终点所面临的挑战与机遇。
