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. 2020 Mar 1;180(3):402-410.
doi: 10.1001/jamainternmed.2019.6390.

Post-Acute Kidney Injury Proteinuria and Subsequent Kidney Disease Progression: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study

Chi-Yuan Hsu  1   2 , Vernon M Chinchilli  3 , Steven Coca  4 , Prasad Devarajan  5 , Nasrollah Ghahramani  6 , Alan S Go  1   2 , Raymond K Hsu  1 , T Alp Ikizler  7 , James Kaufman  8 , Kathleen D Liu  1 , Chirag R Parikh  9 , W Brian Reeves  10 , Mark Wurfel  11 , Michael Zappitelli  12 , Paul L Kimmel  13 , Edward D Siew  7   14 ; ASSESS-AKI Investigators
Affiliations

Post-Acute Kidney Injury Proteinuria and Subsequent Kidney Disease Progression: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study

Chi-Yuan Hsu et al. JAMA Intern Med. .

Abstract

Importance: Among patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are identified for appropriate follow-up.

Objective: To evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function.

Design, setting, and participants: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015.

Exposures: Urine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge.

Main outcomes and measures: Kidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease.

Results: Of the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio [HR], 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression.

Conclusions and relevance: Proteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr C.-y. Hsu reported grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Coca reported personal fees and equity and stock options from RenaltyixAI, personal fees from Takeda, CHF Solutions, Janssen, Goldfinch, Relypsa, and pulseData outside the submitted work. Dr Devarajan is a co-inventor on patents submitted for the use of NGAL as a biomarker of kidney injury, and has licensing agreements with BioPorto, Inc. Dr Ghahramani reported grants from NIH during the conduct of the study. Dr Go reported grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) during the conduct of the study. Dr Ikizler reported personal fees from Fresenius Kabi, Abbott, International Society of Nephrology, and Reata Pharmaceuticals outside the submitted work. Dr Kaufman reported personal fees from NIDDK during the conduct of the study; grant support from Department of Veterans Affairs, Cooperative Studies Program outside the submitted work. Dr Liu reported grants from NIH: National Heart, Lung and Blood Institute, grants from NIDDK, personal fees from Biomerieux, Durect, Theravance, Quark, Potrero Med, stock holdings from Amgen, travel expenses from National Policy Forum on Critical Care and Acute Renal Failure, travel expenses and speaking fees from Baxter, personal fees from Astra Zeneca, associate editor position at the American Thoracic Society, and personal fees from UpToDate outside the submitted work. Dr Parikh reported membership on the advisory board of RenalytixAI and owns equity in the same. He also serves as consultant for Genfit and TriCeda. Dr Wurfel reported grants from NIDDK during the conduct of the study. Dr Kimmel reported being an Editor with Dr Mark Rosenberg of the textbook Chronic Renal Disease. Dr Siew reported honorarium for an educational talk provided at Da Vita Annual Physician conference February, 2019; consulting for Akebia Therapeutics, Inc; royalties as a contributing author for UptoDate; and being an Associate Editor for the Clinical Journal of the American Society of Nephrology. No other disclosures were reported.

Figures

Figure.
Figure.. Kaplan-Meier Curves Showing Time to Kidney Disease Progression (Defined as Halving of eGFR or ESRD) by Quartiles of Urine ACR (UACR) Among the 769 ASSESS-AKI Enrollees With AKI 3 Months Prior to Baseline ASSESS-AKI Study Visit
ACR indicates albumin to creatinine ratio; AKI, acute kidney injury; ASSESS-AKI,the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study; eGFR, estimated glomerular filtration function; ESRD, end-stage renal disease
See this image and copyright information in PMC

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