Candidate Surrogate End Points for ESRD after AKI
2016 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 9, 2851-2859 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
American Society of Nephrology , 2016. Vol. 27, no 9, 2851-2859 p.
acute renal failure, end stage kidney disease, glomerular filtration rate
IdentifiersURN: urn:nbn:se:liu:diva-129985DOI: 10.1681/ASN.2015070829ISI: 000382270500029PubMedID: 26857682OAI: oai:DiVA.org:liu-129985DiVA: diva2:945839
Funding agencies: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K08DK092287]; National Kidney Foundation; National Institutes of Health/NIDDK [R01DK100446, R01DK096920]; Department of VA, Veterans Health Administration, Office of Research and De2016-07-042016-07-042016-10-03Bibliographically approved