title: Candidate Surrogate End Points for ESRD after AKI.
abstract: AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Departments of Epidemiology and mgrams2@jhmi.edu.
authors: Morgan E
authors: ME
authors: Grams
authors: Departments of Epidemiology and.
authors: Yingying
authors: Y
authors: Sang
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Departments of Epidemiology and Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;
authors: Josef
authors: J
authors: Coresh
authors: Departments of Epidemiology and.
authors: Shoshana H
authors: SH
authors: Ballew
authors: Departments of Epidemiology and.
authors: Kunihiro
authors: K
authors: Matsushita
authors: Division of Nephrology, Tufts Medical Center, Boston, Massachusetts;
authors: Andrew S
authors: AS
authors: Levey
authors: Division of Clinical Epidemiology, University of Utah School of Medicine, Salt Lake City, Utah;
authors: Tom H
authors: TH
authors: Greene
authors: Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee;
authors: Miklos Z
authors: MZ
authors: Molnar
authors: Department of Cardiothoracic Surgery and Cardiothoracic Anesthesia, Linköping University Hospital, Linköping, Sweden; Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden;
authors: Zoltan
authors: Z
authors: Szabo
authors: Harold Simmons Center for Chronic Disease Research and Epidemiology and Division of Nephrology and Hypertension, University of California Irvine Medical Center, Irvine, California; and.
authors: Kamyar
authors: K
authors: Kalantar-Zadeh
authors: Division of Nephrology, University of Tennessee Health Science Center, Memphis, Tennessee; Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee.
authors: Csaba P
authors: CP
authors: Kovesdy
mesh_terms: D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology / Q000601:surgery
chemical_list: D015415:Biomarkers; D003404:Creatinine
keywords: acute renal failure; end stage kidney disease; glomerular filtration rate