Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.

Sandeep K. Mallipattu has patent interest intellectual property in Kruppel-Like Factor 15 (KLF15) Small Molecule Agonists in Kidney Disease and is a consultant for (Wildwood Therapeutics). Chirag R. Parikh is a member of the advisory board of and owns equity in RenalytixAI and also serves as a consultant for Genfit and Novartis. Soko Setoguchi received research funding from Pfizer Inc., Pfizer Japan, BMS, and Daiichi Sankyo and served as a consultant for Pfizer Inc, Pfizer Japan, Merck Co. Inc., and Medtronic Inc. All other authors have no conflicts of interest to declare

The study was funded by NCATS U24 TR002306

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The N3C data transfer to NCATS is performed under a Johns Hopkins University Reliance Protocol IRB00249128 or individual site agreements with NIH. The N3C Data Use Request ID is DUR-94BBC49, which was established under approval of the study via exemption at Stony Brook University IRB2020-00687.

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