title: Biomarkers and surrogate endpoints in kidney disease.
abstract: 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.
authors.affiliation: Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA, 19104, USA. hartunge@email.chop.edu.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, 415 Curie Blvd, Philadelphia, PA, 19104, USA. hartunge@email.chop.edu.
authors.forename: Erum A
authors.identifier: http://orcid.org/0000-0001-5617-6505
authors.initials: EA
authors.lastname: Hartung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000378:metabolism*; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers
keywords: Acute kidney injury; Biomarkers; Chronic kidney disease; End-stage renal disease; Polycystic kidney disease; Surrogate endpoints