Association Between Early Recovery of Kidney Function After Acute Kidney Injury and Long-term Clinical Outcomes

Abstract

Importance: The severity of acute kidney injury (AKI) is usually determined based on the maximum serum creatinine concentration. However, the trajectory of kidney function recovery could be an additional important dimension of AKI severity.

Objective: To assess whether the trajectory of kidney function recovery within 72 hours after AKI is associated with long-term risk of clinical outcomes.

Design, setting, and participants: This prospective, multicenter cohort study enrolled 1538 adults with or without AKI 3 months after hospital discharge between December 1, 2009, and February 28, 2015. Statistical analyses were completed November 1, 2018. Participants with or without AKI were matched based on demographic characteristics, site, comorbidities, and prehospitalization estimated glomerular filtration rate. Participants with AKI were classified as having resolving or nonresolving AKI based on previously published definitions. Resolving AKI was defined as a decrease in serum creatinine concentration of 0.3 mg/dL or more or 25% or more from maximum in the first 72 hours after AKI diagnosis. Nonresolving AKI was defined as AKI not meeting the definition for resolving AKI.

Main outcomes and measures: The primary outcome was a composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up.

Results: Among 1538 participants (964 men; mean [SD] age, 64.6 [12.7] years), 769 (50%) had no AKI, 475 (31%) had a resolving AKI pattern, and 294 (19%) had a nonresolving AKI pattern. After a median follow-up of 4.7 years, the outcome of MAKE occurred in 550 (36%) of all participants. The adjusted hazard ratio for MAKE was higher for patients with resolving AKI (adjusted hazard ratio, 1.52; 95% CI, 1.01-2.29; P = .04) and those with nonresolving AKI (adjusted hazard ratio 2.30; 95% CI, 1.52-3.48; P < .001) compared with participants without AKI. Within the population of patients with AKI, nonresolving AKI was associated with a 51% greater risk of MAKE (95% CI, 22%-88%; P < .001) compared with resolving AKI. The higher risk of MAKE among patients with nonresolving AKI was explained by a higher risk of incident and progressive chronic kidney disease.

Conclusions and relevance: This study suggests that the 72-hour period immediately after AKI distinguishes the risk of clinically important kidney-specific long-term outcomes. The identification of different AKI recovery patterns may improve patient risk stratification, facilitate prognostic enrichment in clinical trials, and enable recognition of patients who may benefit from nephrology consultation.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Moledina reported having a patent pending for Systems and Methods to Diagnose Acute Interstitial Nephritis. Dr Coca reported receiving personal fees, equity, and stock options from RenalytixAI; personal fees from Bayer, Relypsa, CHF Solutions, Takeda, Janssen, and Goldfinch; and grants and personal fees from inRegen outside the submitted work. Dr Parikh reported receiving personal fees from Renalytix and Genfit outside the submitted work. Drs Hsu, Go, Ikizler, and Wurfel reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) during the conduct of the study. Dr Ikizler reported receiving personal fees from Abbott, Fresenius Kabi, Reata, and International Society of Nephrology outside the submitted work. Dr Siew reported receiving personal fees from Akebia Inc, Da Vita Inc, UptoDate, and Clinical Journal of the American Society of Nephrology outside the submitted work. Dr Kaufman reported receiving personal fees from NIDDK during the conduct of the study. Dr Kimmel reported receiving royalties for serving as coeditor of Chronic Renal Disease. Dr Himmelfarb reported serving on the scientific advisory board for Renalytix AI and Chinook Therapeutics Inc; and serving as a consultant for Seattle Genetics Inc and Maze Therapeutics Inc. No other disclosures were reported.

Figures

Figure.. Risk of Renal Outcomes

A, Kaplan-Meier plot demonstrates the highest risk for the composite outcome of major adverse kidney events (MAKE) among participants in the group with nonresolving acute kidney injury (AKI), with a stepwise decrease in the risk for MAKE in the group with resolving AKI, and then in participants without AKI. Major adverse kidney events are defined as the composite of chronic kidney disease (CKD) incidence, chronic kidney disease progression, initiation of long-term dialysis, or death from any cause during study follow-up. B, Risk of CKD incidence among patients without CKD at baseline. C, Risk of CKD progression among patients with CKD at baseline. The P value is a log-rank test of the null hypothesis that the survival distribution is the same across the no AKI, resolving AKI, and nonresolving AKI subgroups vs a significant difference in survival.