TY - JOUR
T1 - Candidate surrogate end points for ESRD after AKI
AU - Grams, Morgan E.
AU - Sang, Yingying
AU - Coresh, Josef
AU - Ballew, Shoshana H.
AU - Matsushita, Kunihiro
AU - Levey, Andrew S.
AU - Greene, Tom H.
AU - Molnar, Miklos Z.
AU - Szabo, Zoltan
AU - Kalantar-Zadeh, Kamyar
AU - Kovesdy, Csaba P.
N1 - Publisher Copyright:
Copyright © 2016 by the American Society of Nephrology.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2015070829
DO - 10.1681/ASN.2015070829
M3 - Article
C2 - 26857682
AN - SCOPUS:84964017133
SN - 1046-6673
VL - 27
SP - 2851
EP - 2859
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 9
ER -