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. 2022 Nov 7:55:101724.
doi: 10.1016/j.eclinm.2022.101724. eCollection 2023 Jan.

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Byorn W L Tan  1 , Bryce W Q Tan  1 , Amelia L M Tan  2 , Emily R Schriver  3 , Alba Gutiérrez-Sacristán  2 , Priyam Das  2 , William Yuan  2 , Meghan R Hutch  4 , Noelia García Barrio  5 , Miguel Pedrera Jimenez  5 , Noor Abu-El-Rub  6 , Michele Morris  7 , Bertrand Moal  8 , Guillaume Verdy  8 , Kelly Cho  9 , Yuk-Lam Ho  9 , Lav P Patel  6 , Arianna Dagliati  10 , Antoine Neuraz  11 , Jeffrey G Klann  12 , Andrew M South  13 , Shyam Visweswaran  7 , David A Hanauer  14 , Sarah E Maidlow  15 , Mei Liu  6 , Danielle L Mowery  16 , Ashley Batugo  17 , Adeline Makoudjou  18 , Patric Tippmann  18 , Daniela Zöller  18 , Gabriel A Brat  2 , Yuan Luo  4 , Paul Avillach  2 , Riccardo Bellazzi  10 , Luca Chiovato  19 , Alberto Malovini  20 , Valentina Tibollo  20 , Malarkodi Jebathilagam Samayamuthu  7 , Pablo Serrano Balazote  5 , Zongqi Xia  21 , Ne Hooi Will Loh  22 , Lorenzo Chiudinelli  23 , Clara-Lea Bonzel  2 , Chuan Hong  24   2 , Harrison G Zhang  2 , Griffin M Weber  2 , Isaac S Kohane  2 , Tianxi Cai  2 , Gilbert S Omenn  25 , John H Holmes  16   17 , Kee Yuan Ngiam  26 ; Consortium for Clinical Characterization of COVID-19 by EHR (4CE)
Collaborators, Affiliations

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Byorn W L Tan et al. EClinicalMedicine. .

Abstract

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.

Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.

Findings: Advanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI.

Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery.

Funding: Authors are supported by various funders, with full details stated in the acknowledgement section.

Keywords: Acute kidney injury; COVID-19; Chronic kidney disease; Electronic health records; SARS-CoV-2.

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Conflict of interest statement

Dr Hanauer reported having developed an electronic resource of clinical synonyms, EMERSE, that is licensed by the University of Michigan and receiving a portion of the licensing fees for this resource outside the submitted work. Dr Omenn reported being an early investor and serving on the board of Angion Biomedica Corporation, New York, which has conducted clinical trials of drug candidates for overcoming acute kidney injury following cardiopulmonary surgery or kidney transplantation. The former was terminated early based on unsatisfactory efficacy/adverse effects assessment; the latter had insufficient benefit to warrant proposing a Phase III trial. The company is moving in other directions, to be determined. No further work on kidney is anticipated. Dr Holmes disclosed participation as an NIH/NIDDK T2 Coach R01DK113189. Dr Malovini disclosed being a shareholder of Biomeris s.r.l. Dr Bellazzi reported receiving honoraria from Pfizer, and disclosed being a shareholder of University of Pavia spin-off Biomeris. Dr Klann reports consulting fees from i2b2 tranSMART foundation, for work to enhance open-source data warehouse platform. He reports no direct relationship to this work, except that the data model for analysis in this manuscript was inspired by this platform.

Figures

Fig. 1
Fig. 1
Flow diagram of study construct. Abbreviations: mg/dL: milligram per decilitre; RRT: renal replacement therapy; sCr: serum creatinine.
Fig. 2
Fig. 2
Mortality outcomes of COVID-19 patients with or without AKI. (a) Kaplan–Meier survival curves of COVID-19 patients, stratified by COVID-19-associated AKI occurrence. The p-value was computed from a log-rank test comparing the survival curves. (b) Kaplan–Meier survival curves of COVID-19 patients, stratified by COVID-19-associated AKI KDIGO stage. Dashed lines indicate 75th percentile survival times. The p-value was computed from a log-rank test comparing the survival curves. (c) Corresponding incidence rate ratios (IRRs) for mortality 30-days post-peak serum creatinine, compared to patients with no COVID-19-associated AKI. The dashed horizontal line represents the reference value of 1. Shaded areas and error bars represent the 95% confidence interval. ∗∗∗p < 0.0001 compared to reference range of 1 (no AKI). #p < 0.0001 compared between AKI KDIGO stages. A p-value of <0.05 was considered statistically significant.
Fig. 3
Fig. 3
Kidney function recovery and kidney function impairment outcomes of COVID-19 patients. (a) Cumulative incidence curves of kidney function recovery in the subgroup of COVID-19 patients with AKI, stratified by COVID-19-associated AKI KDIGO stage. Solid lines indicate kidney function recovery, and coloured dashed lines indicate mortality as a competing event. Black dashed lines indicate the median time to kidney function recovery. (b) Cumulative incidence curves of kidney function impairment, defined as a sustained increase in baseline sCr to ≥1.29 mg/dL, in the subgroup of COVID-19 patients without CKD, stratified by COVID-19-associated AKI KDIGO stage. Solid lines indicate kidney function impairment, and coloured dashed lines indicate mortality as a competing event. Black dashed lines indicate the percentage without kidney function impairment at 90 days post-AKI. Shaded areas represent the 95% confidence interval. P-values shown are computed from Gray's test comparing cumulative incidence curves of the event of interest. Abbreviations: KDIGO: Kidney Disease: Improving Global Outcomes; CKD: chronic kidney disease; sCr: serum creatinine; 95%CI: 95% confidence interval.
Fig. 4
Fig. 4
Long-term kidney function recovery outcomes of COVID-19-associated AKI. Forest plots of the risk of COVID-19-associated AKI in long-term kidney function decline, at 90-, 180- and 365-days post-AKI peak (AKI patients) or peak sCr in the first admission (non-AKI patients). Relative kidney function decline at each time point was defined as persistently raised serum creatinine values ≥1.25-fold baseline serum creatinine. Abbreviations: RR: risk ratio; 95%CI: 95% confidence interval.
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