Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19

Jan-Hendrik B Hardenberg; Helena Stockmann; Annette Aigner; Inka Gotthardt; Philipp Enghard; Christian Hinze; Felix Balzer; Danilo Schmidt; Daniel Zickler; Jan Kruse; Roland Körner; Miriam Stegemann; Thomas Schneider; Michael Schumann; Holger Müller-Redetzky; Stefan Angermair; Klemens Budde; Steffen Weber-Carstens; Martin Witzenrath; Sascha Treskatsch; Britta Siegmund; Claudia Spies; Norbert Suttorp; Geraldine Rauch; Kai-Uwe Eckardt; Kai M Schmidt-Ott

doi:10.1016/j.ekir.2021.01.011

Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19

Kidney Int Rep. 2021 Apr;6(4):905-915. doi: 10.1016/j.ekir.2021.01.011. Epub 2021 Feb 2.

Authors

Jan-Hendrik B Hardenberg¹, Helena Stockmann¹, Annette Aigner^{2

3}, Inka Gotthardt¹, Philipp Enghard¹, Christian Hinze¹, Felix Balzer⁴, Danilo Schmidt⁵, Daniel Zickler¹, Jan Kruse¹, Roland Körner¹, Miriam Stegemann⁶, Thomas Schneider⁷, Michael Schumann⁷, Holger Müller-Redetzky⁶, Stefan Angermair⁸, Klemens Budde¹, Steffen Weber-Carstens⁴, Martin Witzenrath⁶, Sascha Treskatsch⁸, Britta Siegmund⁷, Claudia Spies⁴, Norbert Suttorp⁶, Geraldine Rauch^{2

3}, Kai-Uwe Eckardt¹, Kai M Schmidt-Ott^{1

3

9}

Affiliations

¹ Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
² Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
³ Berlin Institute of Health (BIH), Berlin, Germany.
⁴ Department of Anesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁵ Division IT, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁶ Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁷ Department of Gastroenterology, Infectiology and Rheumatology (CBF), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁸ Department of Anesthesiology and Operative Intensive Care Medicine (CBF), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
⁹ Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

Abstract

Introduction: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development.

Methods: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI.

Results: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings.

Conclusion: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.

Keywords: COVID-19; COVID-associated AKI; acute kidney injury; kidney failure.