COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup

doi:10.1038/s41581-020-00356-5

Review

. 2020 Dec;16(12):747-764.

doi: 10.1038/s41581-020-00356-5. Epub 2020 Oct 15.

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup

Mitra K Nadim¹, Lui G Forni^{2

3}, Ravindra L Mehta⁴, Michael J Connor Jr⁵, Kathleen D Liu⁶, Marlies Ostermann⁷, Thomas Rimmelé⁸, Alexander Zarbock⁹, Samira Bell¹⁰, Azra Bihorac¹¹, Vincenzo Cantaluppi¹², Eric Hoste¹³, Faeq Husain-Syed¹⁴, Michael J Germain¹⁵, Stuart L Goldstein¹⁶, Shruti Gupta¹⁷, Michael Joannidis¹⁸, Kianoush Kashani¹⁹, Jay L Koyner²⁰, Matthieu Legrand²¹, Nuttha Lumlertgul^{7

22}, Sumit Mohan^{23

24}, Neesh Pannu²⁵, Zhiyong Peng²⁶, Xose L Perez-Fernandez²⁷, Peter Pickkers²⁸, John Prowle²⁹, Thiago Reis^{30

31}, Nattachai Srisawat^{22

32}, Ashita Tolwani³³, Anitha Vijayan³⁴, Gianluca Villa³⁵, Li Yang³⁶, Claudio Ronco^{30

37}, John A Kellum³⁸

Affiliations

¹ Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK.
³ Intensive Care Unit, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK.
⁴ Division of Nephrology, Department of Medicine, University of California, San Diego, CA, USA.
⁵ Divisions of Pulmonary, Allergy, Critical Care, & Sleep Medicine, Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Divisions of Nephrology and Critical Care Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco, CA, USA.
⁷ Department of Intensive Care, Guy's & St Thomas' NHS Foundation Hospital, London, UK.
⁸ Department of Anesthesiology and Intensive Care Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
⁹ Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
¹⁰ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
¹¹ Department of Medicine, University of Florida, Gainesville, FL, USA.
¹² Nephrology and Kidney Transplantation Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
¹³ Intensive Care Unit, Ghent University Hospital, Ghent University, Ghent, Belgium.
¹⁴ Division of Nephrology, Pulmonology and Critical Care Medicine, Department of Medicine II, University Hospital Giessen and Marburg, Giessen, Germany.
¹⁵ Division of Nephrology, Renal Transplant Associates of New England, Baystate Medical Center U Mass Medical School, Springfield, MA, USA.
¹⁶ Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁷ Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁸ Division of Intensive Care and Emergency Medicine, Department of Medicine, Medical University of Innsbruck, Innsbruck, Austria.
¹⁹ Division of Nephrology and Hypertension, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
²⁰ Division of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
²¹ Department of Anesthesiology and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
²² Division of Nephrology, Excellence Center for Critical Care Nephrology, Critical Care Nephrology Research Unit, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
²³ Department of Medicine, Division of Nephrology, Columbia University College of Physicians & Surgeons and New York Presbyterian Hospital, New York, NY, USA.
²⁴ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
²⁵ Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
²⁶ Division of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
²⁷ Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
²⁸ Department of Intensive Care Medicine, Radboudumc, Nijmegen, The Netherlands.
²⁹ Critical Care and Peri-operative Medicine Research Group, William Harvey Research Institute, Queen Mary University of London, London, UK.
³⁰ Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, International Renal Research Institute of Vicenza, Vicenza, Italy.
³¹ Department of Nephrology, Clínica de Doenças Renais de Brasília, Brasília, Brazil.
³² Academy of Science, Royal Society of Thailand, Bangkok, Thailand.
³³ Division of Nephrology, Department of Medicine, University of Alabama, Birmingham, AL, USA.
³⁴ Division of Nephrology, Washington University School of Medicine, St. Louis, MO, USA.
³⁵ Section of Anaesthesiology and Intensive Care, Department of Health Science, University of Florence, Florence, Italy.
³⁶ Renal Division, Peking University First Hospital, Beijing, China.
³⁷ Department of Medicine, University of Padova, Padova, Italy.
³⁸ Department of Critical Care Medicine, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA. kellumja@upmc.edu.

PMID: 33060844
PMCID: PMC7561246
DOI: 10.1038/s41581-020-00356-5

Review

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup

Mitra K Nadim et al. Nat Rev Nephrol. 2020 Dec.

. 2020 Dec;16(12):747-764.

doi: 10.1038/s41581-020-00356-5. Epub 2020 Oct 15.

Authors

Affiliations

¹ Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK.
³ Intensive Care Unit, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK.
⁴ Division of Nephrology, Department of Medicine, University of California, San Diego, CA, USA.
⁵ Divisions of Pulmonary, Allergy, Critical Care, & Sleep Medicine, Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Divisions of Nephrology and Critical Care Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco, CA, USA.
⁷ Department of Intensive Care, Guy's & St Thomas' NHS Foundation Hospital, London, UK.
⁸ Department of Anesthesiology and Intensive Care Medicine, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
⁹ Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.
¹⁰ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
¹¹ Department of Medicine, University of Florida, Gainesville, FL, USA.
¹² Nephrology and Kidney Transplantation Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
¹³ Intensive Care Unit, Ghent University Hospital, Ghent University, Ghent, Belgium.
¹⁴ Division of Nephrology, Pulmonology and Critical Care Medicine, Department of Medicine II, University Hospital Giessen and Marburg, Giessen, Germany.
¹⁵ Division of Nephrology, Renal Transplant Associates of New England, Baystate Medical Center U Mass Medical School, Springfield, MA, USA.
¹⁶ Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁷ Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁸ Division of Intensive Care and Emergency Medicine, Department of Medicine, Medical University of Innsbruck, Innsbruck, Austria.
¹⁹ Division of Nephrology and Hypertension, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
²⁰ Division of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
²¹ Department of Anesthesiology and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
²² Division of Nephrology, Excellence Center for Critical Care Nephrology, Critical Care Nephrology Research Unit, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand.
²³ Department of Medicine, Division of Nephrology, Columbia University College of Physicians & Surgeons and New York Presbyterian Hospital, New York, NY, USA.
²⁴ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
²⁵ Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
²⁶ Division of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
²⁷ Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
²⁸ Department of Intensive Care Medicine, Radboudumc, Nijmegen, The Netherlands.
²⁹ Critical Care and Peri-operative Medicine Research Group, William Harvey Research Institute, Queen Mary University of London, London, UK.
³⁰ Department of Nephrology, Dialysis and Transplantation, San Bortolo Hospital, International Renal Research Institute of Vicenza, Vicenza, Italy.
³¹ Department of Nephrology, Clínica de Doenças Renais de Brasília, Brasília, Brazil.
³² Academy of Science, Royal Society of Thailand, Bangkok, Thailand.
³³ Division of Nephrology, Department of Medicine, University of Alabama, Birmingham, AL, USA.
³⁴ Division of Nephrology, Washington University School of Medicine, St. Louis, MO, USA.
³⁵ Section of Anaesthesiology and Intensive Care, Department of Health Science, University of Florence, Florence, Italy.
³⁶ Renal Division, Peking University First Hospital, Beijing, China.
³⁷ Department of Medicine, University of Padova, Padova, Italy.
³⁸ Department of Critical Care Medicine, Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA. kellumja@upmc.edu.

PMID: 33060844
PMCID: PMC7561246
DOI: 10.1038/s41581-020-00356-5

Erratum in

Publisher Correction: COVID-19-associated acute kidney injury: consensus report of the 25^th Acute Disease Quality Initiative (ADQI) Workgroup.
Nadim MK, Forni LG, Mehta RL, Connor MJ Jr, Liu KD, Ostermann M, Rimmelé T, Zarbock A, Bell S, Bihorac A, Cantaluppi V, Hoste E, Husain-Syed F, Germain MJ, Goldstein SL, Gupta S, Joannidis M, Kashani K, Koyner JL, Legrand M, Lumlertgul N, Mohan S, Pannu N, Peng Z, Perez-Fernandez XL, Pickkers P, Prowle J, Reis T, Srisawat N, Tolwani A, Vijayan A, Villa G, Yang L, Ronco C, Kellum JA. Nadim MK, et al. Nat Rev Nephrol. 2020 Dec;16(12):765. doi: 10.1038/s41581-020-00372-5. Nat Rev Nephrol. 2020. PMID: 33139940 Free PMC article.

Abstract

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

PubMed Disclaimer

Conflict of interest statement

L.G.F. has received grant and/or research support from Baxter and speaker’s honoraria from bioMérieux and Ortho Clinical diagnostics. R.L.M. has received grant and/or research support from Fresenius and Fresenius-Kabi and consulting fees from AM-Pharma, Sphingotec, Akebia, GE healthcare, Indalo, bioMérieux, Intercept, Baxter, Medtronic and Mallinckrodt. M.J.C. has received grant and/or research support from NIH and Potrero Medical Inc. K.D.L. has received consulting fees from bioMérieux and Durect. M.O. has received grant and/or research support from Baxter. T. Rimmelé has received grant and/or research support from Baxter and consulting fees from Baxter, Fresenius Medical Care, bioMérieux, Braun and Nikkiso. A.Z. has received grant and/or research support from Astute Medical, Fresenius, Baxter, Astellas, DFG, EK and consulting fees from Baxter, Astute Medical, bioMérieux, La Jolla Pharmaceuticals, Fresenius, Braun, AM-Pharma, Astellas and Radiopharma. S.L.G. has grant and/or research support and consulting fees from ExThera, BioPorto, Baxter and SeaStar, speaker’s honoraria from Baxter and Fresenius and is a stockholder for MediBeacon. S.G. has received consulting fees from GlaxoSmithKline. M.J. has received grant and/or research support from Baxter. J.L.K. has received grant and/or research support from NxStage, Satellite Health Care, and consulting fees from Astute Medical, Baxter, Sphingotec, and honoraria from the American Society of Nephrology. M.L. has received grant and/or research support from Sphingotec and consulting fees from Novartis. S.M. has received consulting fees from Angion Biomedica. X.L.P.-F. has received speaker’s honoraria from Baxter. P.P. has received travel and consulting fees from AM-Pharma, EBI and Sphingotec. J.P. has received grant and/or research support from bioMérieux, consulting fees from Quark Pharmaceutical and Medibeacon Inc., and speaker’s honoraria from Nikkiso Europe GmbH, Baxter, Braun Medical Ltd, Fresenius Medical Care and Fresenius-Kabi UK. T. Reis. has received consulting fees from Baxter and Eurofarma and speaker’s honoraria from Baxter and Braun. N.S. has received grant and/or research support from Baxter. A.T. has received consulting fees and speaker’s honoraria from Baxter and has a patent on 0.5% citrate solution for continuous renal replacement therapy. A.V. has received consulting fees for NxStage and has received other fees from Boehringer Ingelheim. G.V. has received grant and/or research support from Baxter SpA. C.R. has received consulting fees from Baxter, Jfron, bioMérieux, Medtronic and speaker’s honoraria from GE, OCD, and Cytosorbents. J.A.K. has received grant and/or research support from Astellas, Astute Medical, Baxter, bioMérieux, Cytosorbents, RenalSense, consulting fees from Astellas, Astute Medical, Baxter, bioMérieux, Cytosorbents, RenalSense, DaVita, Fresenius, Mallinckrodt, NxStage, Potrero, and has licensing of intellectual property for Astute Medical and Cytosorbents. The other authors declare no competing interests.

Figures

**Fig. 1. Pathogenesis of COVID-19 AKI.**
a,b | The pathogenesis of AKI in patients with COVID-19 (COVID-19 AKI) is likely multifactorial, involving both the direct effects of the SARS-CoV-2 virus on the kidney and the indirect mechanisms resulting from systemic consequences of viral infection or effects of the virus on distant organs including the lung, in addition to mechanisms relating to the management of COVID-19. AKI, acute kidney injury. Adapted from Acute Disease Quality Initiative 25, www.ADQI.org, CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/).

**Fig. 2. Stage-based management of COVID-19 AKI.**
The pathogenesis of acute kidney injury (AKI) in patients with COVID-19 (COVID-19 AKI) likely involves direct viral effects, indirect effects and sequelae from disease management. There is no specific evidence to suggest that COVID-19 AKI should be managed differently from other causes of AKI in critically ill patients; however, the possible underlying disease mechanisms should be taken into account when considering approaches to the management of COVID-19 AKI throughout the disease course. Adapted with permission from ref., Elsevier, and Acute Disease Quality Initiative 25, www.ADQI.org, CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/).

**Fig. 3. Step-wise plan to prepare for a surge in RRT demand during a pandemic or disaster.**
A sudden spike in cases of COVID-19 disease might cause unforeseen shortages of renal replacement therapy (RRT) devices and/or RRT disposables and fluids. In addition, supply chain security might be compromised, further contributing to local shortages. As part of a local surge response, use of a wider variety of acute RRT modalities may be needed to maximize the number of patients who can receive RRT. Adapted from Acute Disease Quality Initiative 25, www.ADQI.org, CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/).

**Fig. 4. Potential extracorporeal blood purification treatment options based on underlying COVID-19 pathophysiology.**
Extracorporeal blood purification (EBP) has been proposed as a possible adjuvant therapy for critically ill patients with COVID-19 on the basis that removal of circulating immunomodulatory factors, that might contribute to disease processes and/or the development of multiple organ failure, might improve outcomes. Of note, the efficacy of EBP in patients with COVID-19 and/or COVID-19 AKI has not been tested, and all therapeutic options must therefore be tested in clinical trials in the context of COVID-19. EBP therapies should be considered complementary to pharmacological support. EBP therapies may also be considered in sequence or as separate entities according to current evidence or pathophysiological rationale, as changes in pathophysiology over the disease course might indicate different treatment approaches. AKI, acute kidney injury; ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; DAMPs, damage-associated molecular patterns; HCO, high cut-off; HP, haemoperfusion; MCO, medium cut-off; PAMPs, pathogen-associated molecular patterns; RRT, renal replacement therapy; TPE, therapeutic plasma exchange. Adapted from Acute Disease Quality Initiative 25, www.ADQI.org, CC BY 2.0 (https://creativecommons.org/licenses/by/2.0/).

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[1] Zhu N, et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed

[2] Zhu N, et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed

[3] Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. - PMC - PubMed

[4] Wang D, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069. - PMC - PubMed

[5] Wang L, et al. Coronavirus disease 19 infection does not result in acute kidney injury: an analysis of 116 hospitalized patients from Wuhan, China. Am. J. Nephrol. 2020;51:343–348. - PMC - PubMed

[6] Wang L, et al. Coronavirus disease 19 infection does not result in acute kidney injury: an analysis of 116 hospitalized patients from Wuhan, China. Am. J. Nephrol. 2020;51:343–348. - PMC - PubMed

[7] Chen N, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513. - PMC - PubMed

[8] Chen N, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513. - PMC - PubMed

[9] Cheng Y, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:829–838. - PMC - PubMed

[10] Cheng Y, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:829–838. - PMC - PubMed

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COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup

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COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup

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