Candidate surrogate end points for ESRD after AKI

Morgan E. Grams, Yingying Sang, Josef Coresh, Shoshana H. Ballew, Kunihiro Matsushita, Andrew S. Levey, Tom H. Greene, Miklos Z. Molnar, Zoltan Szabo, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy

Research output: Contribution to journalArticle

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 undergoingmajor surgery between 2004 and 2011,we characterized in-hospitalAKI by KidneyDisease ImprovingGlobalOutcomes 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 of30%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 patientswith in-hospital AKI comparedwith 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 mortalitywere 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.

Original languageEnglish (US)
Pages (from-to)2851-2859
Number of pages9
JournalJournal of the American Society of Nephrology
Volume27
Issue number9
DOIs
StatePublished - Jan 1 2016

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ASJC Scopus subject areas

  • Nephrology

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