CLINICAL RESEARCH www.jasn.

org

AKI Treated with Renal Replacement Therapy in

Critically Ill Patients with COVID-19
Shruti Gupta ,1 Steven G. Coca ,2 Lili Chan,2 Michal L. Melamed,3
Samantha K. Brenner,4,5 Salim S. Hayek ,6 Anne Sutherland,7 Sonika Puri,8
Anand Srivastava,9 Amanda Leonberg-Yoo,10 Alexandre M. Shehata,11
Jennifer E. Flythe,12,13 Arash Rashidi,14 Edward J. Schenck,15 Nitender Goyal,16
S. Susan Hedayati,17 Rajany Dy,18 Anip Bansal,19 Ambarish Athavale,20 H. Bryant Nguyen,21
Anitha Vijayan,22 David M. Charytan ,23 Carl E. Schulze,24 Min J. Joo,25
Allon N. Friedman,26 Jingjing Zhang,27 Marie Anne Sosa,28 Eric Judd,29
Juan Carlos Q. Velez,30,31 Mary Mallappallil,32 Roberta E. Redfern,33 Amar D. Bansal,34
Javier A. Neyra,35 Kathleen D. Liu,36 Amanda D. Renaghan,37 Marta Christov,38
Miklos Z. Molnar ,39 Shreyak Sharma,1 Omer Kamal,1 Jeffery Owusu Boateng,40
Samuel A.P. Short ,41 Andrew J. Admon,42 Meghan E. Sise,43 Wei Wang,44,45
Chirag R. Parikh ,46 David E. Leaf ,1 and the STOP-COVID Investigators*
Due to the number of contributing authors, the affiliations are listed at the end of this article.

ABSTRACT
Background AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have
focused on AKI treated with RRT (AKI-RRT).
Methods We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to
intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regres-
sion to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day
mortality among such patients.
Results A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of
whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD,
men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher D-dimer, and
greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-
RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater
regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1–123 days), 403 of the
637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hos-
pitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39
(18.1%) remained RRT dependent 60 days after ICU admission.
Conclusions AKI-RRT is common among critically ill patients with COVID-19 and is associated with a
hospital mortality rate of .60%. Among those who survive to discharge, one in three still depends on
RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

JASN 32: 161–176, 2021. doi: https://doi.org/10.1681/ASN.2020060897

The coronavirus disease 2019 (COVID-19) is pre-
dominantly a respiratory disorder, but much of the
morbidity and mortality associated with severe illness
from COVID-19 has been attributed to injury to
other organs, including the heart1–3 and kidneys.4,5
AKI is emerging as a common and important sequela
of COVID-19, with rates as high as 33%–43% among
hospitalized patients.5,6 Mechanisms that have been
proposed to account for the high rates of AKI ob-
served in patients with COVID-19 include ischemic

JASN 32: 161–176, 2021 ISSN : 1046-6673/3201-161 161

 CLINICAL RESEARCH www.jasn.org
acute tubular necrosis,5,7 cytokine storm,8 and direct viral in-
vasion of the renal proximal tubular cells and podocytes.7,9 Ad-
ditional potential mechanisms include hemodynamic changes
associated with invasive mechanical ventilation5 and concomi-
tant use of antibiotics and antiviral medications with nephro-
toxic potential.
Existing data on COVID-19–associated AKI are incom-
plete. Most studies have been single center or have focused
on single geographic regions, and therefore, they have limited
generalizability.5,10,11 Moreover, few studies have focused on
AKI treated with RRT (AKI-RRT),10 the most severe and clin-
ically relevant form of AKI. AKI-RRT is both resource inten-
sive12 and associated with acute mortality rates as high as 63%
in patients without COVID-19.13,14 Granular, nationally rep-
resentative data on AKI-RRT in patients with COVID-19 are
urgently needed to inform clinical decision making and re-
source allocation.
To address these knowledge gaps, we conducted the Study
of the Treatment and Outcomes in Critically Ill Patients with
COVID-19 (STOP-COVID). STOP-COVID is a multicenter
cohort study examining the demographics, comorbidities, or-
gan dysfunction, treatments, and outcomes of critically ill pa-
tients with COVID-19 admitted to intensive care units (ICUs)
at 67 geographically diverse hospitals across the United
States.15 Here, we report the incidence, clinical features, pa-
tient- and hospital-level risk factors, and outcomes associated
with AKI-RRT among critically ill patients with COVID-19.
Received June 25, 2020. Accepted August 27, 2020.
*The STOP-COVID Investigators are Carl P. Walther, Samaya J. Anumudu,
Justin Arunthamakun, Kathleen F. Kopecky, Gregory P. Milligan, Peter A.
McCullough, Thuy-Duyen Nguyen, Shahzad Shaefi, Megan L. Krajewski, Sid-
harth Shankar, Ameeka Pannu, Juan D. Valencia, Sushrut S. Waikar, Zoe A.
Kibbelaar, Peter Hart, Shristi Upadhyay, Ishaan Vohra, Adam Green, Jean-
Sebastien Rachoin, Christa A. Schorr, Lisa Shea, Daniel L. Edmonston, Chris-
topher L. Mosher, Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo,
Noor ul aain Bhatti, Bijal Mehta, Aquino Williams, Patricia Walters, Ronaldo C.
Go, Keith M. Rose, Rebecca Lisk, Amy M. Zhou, Ethan C. Kim, Kusum S.
Mathews, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali
Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni,
Pattharawin Pattharanitima, Emily J. Gallagher, John Guirguis, Rajat Kapoor,
Christopher Meshberger, Katherine J. Kelly, Brian T. Garibaldi, Celia P. Co-
rona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Elena Cer-
vantes, Samir Gautam, Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku,
Ibrahim Mohamed, Siddartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna
Bhattacharya, John Wagner, Leon Boudourakis, Afshin Ahoubim, Leslie F.
Thomas, Dheeraj Reddy Sirganagari, Pramod K. Guru, Yan Zhou, Paul A. Bergl,
Jesus Rodriguez, Jatan A. Shah, Mrigank S. Gupta, Princy N. Kumar, Deepa G.
Lazarous, Seble G. Kassaye, Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi,
Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina
Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang,
Jyotsana Thakkar, Ritesh Raichoudhury, Akshay Athreya, Mohamed Farag, Soo
Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di
Pan, Stefi Lee, Jamuna Krishnan, William Whalen, Ashley Macina, Sobaata
Chaudhry, Benjamin Wu, Frank Modersitzki, Amey Bhivshet, Alexander S.
Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, Alex-
ander J. Hodakowski, Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna
E. Hasty, Muner M.B. Mohamed, Rupali S. Avasare, David Zonies, Erik T.
Newman, Samah Abu Omar, Kapil K. Pokharel, Harkarandeep Singh, Simon
Correa, Tanveer Shaukat, Heather Yang Meghan Lee, Ian A. Strohbehn, Jiahua
Li, Ariel L. Mueller, Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell
162 JASN
Significance Statement
Although AKI is an important sequela of coronavirus disease 2019
(COVID-19), data on AKI treated with RRT (AKI-RRT) in patients with
COVID-19 are limited. In a multicenter cohort study of 3099 criti-
cally ill adults with COVID-19 admitted to intensive care units (ICUs)
at 67 hospitals across the United States, one in five patients de-
veloped AKI-RRT, 63% of whom died during hospitalization.
Among patients who survived to hospital discharge, one in three
remained RRT dependent at discharge, and one in six remained RRT
dependent 60 days after ICU admission. The study identified sev-
eral patient-and hospital-level risk factors for AKI-RRT and death.
AKI-RRT is common among critically ill patients with COVID-19 and
is associated with high mortality and persistent RRT dependence.
METHODS
Study Design, Oversight, and Patient Population
We conducted STOP-COVID, a multicenter cohort study that
enrolled consecutive adults ($18 years old) with laboratory-
confirmed COVID-19 admitted to ICUs at 67 hospitals across
the United States (Supplemental Table 1). STOP-COVID only
included patients in the ICU in an effort to focus on the pa-
tients at highest risk of acute organ injury and death. The study
was approved with a waiver of informed consent by the in-
stitutional review board at each participating site and regis-
tered on ClinicalTrials.gov (NCT04343898). The primary
findings from STOP-COVID are reported elsewhere.15 For
this study, we included patients admitted to ICUs between
Hall, Laura Bickley, Chris Rowan, Farah Madhai-Lovely, Vasil Peev, Jochen
Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P.
Patel, Joy-Marie Hermes, Amee Patrawalla, Diana G. Finkel, Barbara A. Danek,
Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, Mark Liotta, Jared
Radbel, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, Jayanth
S. Vatson, Shuchi Anand, Joseph E. Levitt, Pablo Garcia, Suzanne M. Boyle, Rui
Song, Ali Arif, Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, Kath-
arine Senter, Moh’d A. Sharshir, Vadym V. Rusnak, Muhammad Imran Ali, Terri
Peters, Kathy Hughes, Amber S. Podoll, Michel Chonchol, Sunita Sharma, Ellen
L. Burnham, Rana Hejal, Laura Latta, Ashita Tolwani, Timothy E. Albertson,
Jason Y. Adams, Steven Y. Chang, Rebecca M. Beutler, Etienne Macedo, Harin
Rhee, Vasantha K. Jotwani, Jay L. Koyner, Chintan V. Shah, Vishal Jaikar-
ansingh, Stephanie M. Toth-Manikowski, James P. Lash, Nourhan Chaaban,
Yahya Ahmad, Madona Elias, Alfredo Iardino, Elizabeth H. Au, Jill H. Sharma,
Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni,
Hayley B. Gershengorn, Pennelope Blakely, Hanna Berlin, Tariq U. Azam,
Husam Shadid, Michael Pan, Patrick O.’ Hayer, Chelsea Meloche, Rafey Feroze,
Kishan J. Padalia, Abbas Bitar, Elizabeth Anderson, John P. Donnelly, Matthew
J. Tugman, Emily H. Chang, Brent R. Brown, Ryan C. Spiardi, Todd A. Miano,
Meaghan S. Roche, Charles R. Vasquez, Natalie C. Ernecoff, Sanjana Kapoor,
Siddharth Verma, Huiwen Chen, Csaba P. Kovesdy, Ambreen Azhar, Mridula V.
Nadamuni, Shani Shastri, Duwayne L. Willett, Kyle B. Enfield, Pavan K. Bha-
traju, A. Bilal Malik, Matthew W. Semler, Christina Mariyam Joy, Tingting Li,
Seth Goldberg, Patricia F. Kao, Greg L. Schumaker, Anthony J. Faugno, Greg L.
Schumaker, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar,
Daniel E. Weiner, Jennifer Griffiths, Sanjeev Gupta, Aromma Kapoor, Perry
Wilson, Tanima Arora, and Ugochukwu Ugwuowo.
Published online ahead of print. Publication date available at www.jasn.org.
Correspondence: Dr. David E. Leaf, Division of Renal Medicine, Brigham and
Women’s Hospital, 75 Francis Street, Boston, MA 02115. Email: DELEAF@bwh.
harvard.edu
Copyright © 2021 by the American Society of Nephrology
JASN 32: 161–176, 2021

March 4 and April 11, 2020, and we followed patients until the
first of hospital discharge, death, or August 1, 2020. We ex-
cluded patients with a history of ESKD.
Data Collection
Study personnel at each site collected data by detailed chart
review and used a standardized patient report form to enter
data into a secure online database (REDCap). Patient-level
data included demographics and comorbidities; longitudinal
laboratory values, physiologic parameters, medications, treat-
ments, and organ support (including RRT) for the first 14 days
following ICU admission; and clinical outcomes, including
acute organ injury and death. Baseline serum creatinine
(SCr) was defined as the lowest value 365–7 days prior to
hospitalization. If a prehospital baseline SCr was not available,
we used the SCr value on hospital admission as the baseline.
We calculated baseline eGFR using the Chronic Kidney Dis-
ease Epidemiology Collaboration equation.16
For patients with AKI-RRT, we recorded the initial RRT mo-
dality (continuous, intermittent, or other) as well as data on RRT
dependence and kidney function at hospital discharge among
survivors. We also collected hospital-level data, including the city
and state of each hospital, hospital size (assessed by the number
of pre–COVID-19 ICU beds, not including surge capacity beds),
and the regional density of COVID-19. We assessed regional
density of COVID-19 by categorizing hospitals into quartiles
according to the regional (county) density of COVID-19 cases
present on the median date of ICU admission for the patients
enrolled at that hospital. A higher quartile signified a greater
regional density of COVID-19. All data were validated through
a series of automated and manual verifications (Supplemental
Material). A complete list of variables is provided in the patient
report form, which is available elsewhere.15
Primary Outcome
The primary outcome was AKI-RRT occurring within 14 days
following ICU admission.
Secondary Outcomes
Secondary outcomes included 28-day mortality and kidney
function at hospital discharge among patients with AKI-
RRT who survived to discharge. Patients who were indepen-
dent of RRT at hospital discharge were classified as having
complete or partial renal recovery if their SCr was #0.35 or
.0.35 mg/dl above their baseline value, respectively. 17,18
Among patients who remained RRT dependent on discharge,
we also obtained RRT dependence data 60 days after ICU ad-
mission. Other outcomes included AKI and its severity occur-
ring on hospital admission and within 14 days following ICU
admission (additional details are provided in Supplemental
Material).
Statistical Analyses
Continuous variables are expressed as median and
interquartile range, and categorical variables are expressed
JASN 32: 161–176, 2021
www.jasn.org CLINICAL RESEARCH
as count and percentage. We used multivariable logistic re-
gression to identify patient- and hospital-level risk factors
for AKI-RRT. We prespecified the following covariates on
the basis of clinical knowledge and prior studies4,5,10,11,19:
demographics (age, sex, race, body mass index, hyperten-
sion, diabetes mellitus, active malignancy, coronary artery
disease, congestive heart failure, and CKD; the latter is clas-
sified as no CKD [eGFR$60 ml/min per 1.73 m 2], CKD
stage 3 [eGFR530–59 ml/min per 1.73 m2], and CKD stages
4 and 5 [eGFR,30 ml/min per 1.73 m2]); the number of
days from hospital to ICU admission (#3 versus .3 days);
acute severity of illness covariates assessed on ICU admis-
sion (lymphocyte count, D-dimer, shock, the ratio of the
partial pressure of arterial oxygen over the fraction of in-
spired oxygen [PaO2:FiO2], the coagulation and liver com-
ponents of the Sequential Organ Failure Assessment score,
altered mental status, and secondary infection); and hospital
characteristics (the number of pre–COVID-19 ICU beds and
the regional density of COVID-19). Covariates are described
in further detail in Supplemental Material and Supplemental
Table 2.
For the primary analysis examining risk factors for AKI-
RRT, we conducted a series of sensitivity analyses. First, we
used generalized estimating equation methods to account
for clustering of patients within hospitals.20 Second, we lim-
ited the analysis to patients with a prehospital baseline SCr
value available. Third, we excluded patients who were trans-
ferred from an outside hospital prior to ICU admission.
Fourth, because death is a competing risk for AKI-RRT, we
limited the analysis to patients who remained alive for the
first 14 days following ICU admission. Fifth, as an alternative
method to account for death as a competing risk, we exam-
ined the composite outcome of AKI-RRT or death (RRT/
death) within 14 days following ICU admission.21–24
Among patients with AKI-RRT, we used multivariable
logistic regression to examine risk factors for 28-day in-
hospital mortality, with the day of ICU admission serving
as time 0 (in a sensitivity analysis, we used the day of RRT
initiation as time 0). Patients who were discharged alive
from the hospital prior to 28 days were considered to be
alive at 28 days (we tested the validity of this assumption
in a subset of patients described further in Supplemental
Material). We selected similar covariates as those described
above in addition to oliguria, number of vasopressors, and
modality of RRT, each of which has been included in prior
risk prediction models for death in critically patients with
AKI-RRT.25 These acute severity of illness covariates were
assessed on the day of RRT initiation or if unavailable, on
the day prior.
To assess interhospital variation in treatments and out-
comes, we used multilevel conditional logistic regression
modeling with patients nested in hospitals to characterize
hospital-level variation and to estimate hospital-specific rates
of AKI-RRT. Additional details are provided in Supplemental
Material.
AKI-RRT in COVID-19 163
 CLINICAL RESEARCH www.jasn.org

Critically ill adults with COVID-19 admitted to

ICUs between March 4 and April 11, 2020
(n=3193)

Excluded ESKD
(n=94)

Patients at risk for AKI

(n=3099)

AKI-RRT No AKI-RRT
(n=637) (n=2462)

Still hospitalized Discharged Died No AKI AKI Stage 1 AKI Stage 2 AKI Stage 3
(n=18) (n=216) (n=403) (n=1414) (n=355) (n=338) (n=355)

RRT-dependent on RRT-independent on
discharge discharge
(n=73) (n=143)

Dead, Alive, Unknown, Complete Partial renal

Day 60 Day 60 Day 60 renal recovery recovery
(n=1) (n=69) (n=3) (n=86) (n=57)

RRT- RRT- Unknown

Independent Dependent RRT Status
at Day 60 at Day 60 at Day 60
(n=24) (n=39) (n=6)

Figure 1. Flowchart of study population. This figure shows the number of patients with and without AKI-RRT and, among those with
AKI-RRT, the number of patients who died, were discharged, and were still hospitalized at last follow up.

Analyses were performed using SAS software version 9.4
(SAS Institute) and Stata 16.1 (StataCorp LLC, College
Station, TX).
RESULTS
Patient Characteristics at Baseline
The initial study population included 3193 patients from 67
centers. We excluded 94 patients (2.9%) with ESKD, resulting
in 3099 patients who met eligibility criteria (Figure 1). A total
of 637 of the 3099 patients (20.6%) developed AKI-RRT
within 14 days following ICU admission. Supplemental
Figure 1 shows the geographic distribution and density of pa-
tients with AKI-RRT among each of the 67 centers.
Baseline characteristics in patients with and without AKI-
RRT are shown in Table 1, and a complete list of base-
line characteristics across all AKI stages is shown in
Supplemental Table 3. Patients with AKI-RRT were similar
in age to patients without AKI-RRT, and they were more likely

164 JASN JASN 32: 161–176, 2021

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Table 1. Patient characteristics at baseline

Characteristic All Patients, n53099 No AKI-RRT, n52462 AKI-RRT, n5637 P Value
Demographics
Age, yr, median (IQR) 62 (51–71) 62 (51–72) 62 (52–69) 0.15
Men, no. (%) 2003 (64.6) 1546 (63.8) 457 (71.7) ,0.001
Race, no. (%) ,0.001
White 1154 (37.2) 981 (39.8) 173 (27.2)
Black 952 (30.7) 672 (27.3) 280 (44.0)
Asian 190 (6.1) 163 (6.6) 27 (4.2)
Other/unknown 803 (25.9) 646 (26.2) 157 (24.7)
Hispanic, no. (%) 1045 (33.7) 853 (34.6) 192 (30.1)
Body mass index, median (IQR) 30.4 (26.6–36.1) 29.8 (26.1–35.2) 32.6 (28.2–39.3) ,0.001
Coexisting conditions, no. (%)a
Diabetes mellitus, insulin dependent 419 (13.5) 304 (12.3) 115 (18.1) ,0.001
Diabetes mellitus, noninsulin dependent 811 (26.2) 588 (23.9) 223 (35.0) ,0.001
Hypertension 1869 (60.3) 1412 (57.4) 457 (71.7) ,0.001
Chronic obstructive pulmonary disease 258 (8.3) 203 (8.2) 55 (8.6) 0.75
Current or former smoker 917 (29.6) 736 (29.9) 181 (28.4) 0.53
Coronary artery disease 390 (12.6) 305 (12.4) 85 (13.3) 0.50
Congestive heart failure 270 (8.7) 200 (8.1) 70 (11.0) 0.02
Chronic liver disease 104 (3.4) 77 (3.1) 27 (4.2) 0.17
Active malignancy 158 (5.1) 126 (5.1) 32 (5.0) 0.92
Kidney transplant 58 (1.9) 37 (1.5) 21 (3.3) 0.005
CKD, ml/min per 1.73 m2 ,0.001
eGFR$90 1033 (33.3) 887 (36.0) 146 (22.9)
eGFR560–89 1164 (37.6) 948 (38.5) 219 (34.4)
eGFR545–59 419 (13.5) 323 (13.1) 96 (15.1)
eGFR530–44 255 (8.2) 189 (7.7) 66 (10.4)
eGFR515–29 159 (5.2) 96 (3.9) 64 (10.1)
eGFR,15 64 (2.1) 19 (0.8) 46 (7.2)
Home medications, no. (%)
Immunosuppressive medication 312 (10.7) 246 (10.0) 66 (10.4) 0.77
ACE-I 566 (18.3) 431 (17.5) 135 (21.2) 0.03
ARB 513 (16.6) 359 (14.6) 154 (24.2) ,0.001
Mineralocorticoid receptor antagonist 81 (2.6) 62 (2.5) 19 (3.0) 0.49
Statin 1156 (37.3) 885 (35.9) 271 (42.5) 0.002
NSAID 260 (8.4) 199 (8.1) 61 (9.6) 0.23
Aspirin 664 (21.4) 510 (20.7) 154 (24.2) 0.07
Anticoagulant 272 (8.8) 230 (9.3) 42 (6.6) 0.03
Vital signs on ICU admission, median (IQR)
Temperature, °C 38.1 (37.3–38.9) 38.0 (37.3–38.9) 38.2 (37.4–39.0) 0.002
Systolic BP, mm Hg 97 (86–111) 97 (86–111) 95 (84–111) 0.21
Heart rate, beats per min 104 (90–120) 104 (90–119) 108 (93–122) ,0.001
Urine output, ml/d 725 (350–1250) 800 (430–1325) 500 (200–930) ,0.001
Laboratory findings on ICU admission, median (IQR)
White cell count, per mm3 8.2 (5.9–11.5) 8.0 (5.8–11.3) 8.9 (6.5–12.2) ,0.001
Lymphocyte count, per mm3 824 (561–1152) 826 (565–1153) 796 (541–1148) 0.26
Hemoglobin, g/dl 12.7 (11.2–14.1) 12.7 (11.3–14.1) 12.6 (10.9–14.0) 0.02
Platelet count, K/mm3 214 (164–272) 215 (164–274) 207 (164–260) 0.08
Creatinine, mg/dl 1.04 (0.80–1.55) 1.00 (0.77–1.38) 1.47 (1.0–2.85) ,0.001
Total bilirubin, mg/dl 0.6 (0.4–0.8) 0.6 (0.4–0.8) 0.6 (0.4–0.8) 0.26
D-dimer, ng/ml 1310 (700–3263) 1180 (670–2620) 2000 (869–6998) ,0.001
C-reactive protein, mg/L 157 (90–237) 154 (87–231) 175 (104–269) ,0.001
IL-6, pg/ml 56 (19–154) 50 (18–50) 100 (29–251) ,0.001
Severity of illness on ICU admission
Invasive mechanical ventilation, no. (%) 2044 (66.0) 1540 (62.6) 504 (79.1) ,0.001
FiO2, median (IQR) 0.8 (0.6–1.0) 0.8 (0.5–1.0) 0.9 (0.6–1.0) ,0.001
PEEP, cm of water, median (IQR) 12 (10–15) 12 (10–15) 14 (10–16) ,0.001

JASN 32: 161–176, 2021 AKI-RRT in COVID-19 165

 CLINICAL RESEARCH www.jasn.org
Table 1. Continued
Characteristic
PaO2:FiO2, mm Hg, median (IQR) b
Noninvasive mechanical ventilation, no. (%)
High-flow nasal cannula or NRB, no. (%)
Altered mental status on ICU day 1, no. (%)
Vasopressors, no. (%)
IQR, interquartile range; ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; NSAID, nonsteroidal anti-inflammatory drug; FiO2,
fraction of inspired oxygen; PEEP, positive end expiratory pressure; NRB, non-rebreather.
a
The definitions of the coexisting disorders are provided in Supplemental Material.
b
PaO2:FiO2 was only assessed in patients receiving invasive mechanical ventilation.
to be men, to be Black, and to have a higher body mass index
(Table 1). Patients with AKI-RRTwere also more likely to have
coexisting conditions, such as diabetes mellitus, hypertension,
and CKD, and to have greater severity of illness on arrival to
the ICU, including higher rates of invasive mechanical venti-
lation and treatment with vasopressors (Table 1).
Characteristics of AKI-RRT
The median time from ICU admission to RRT initiation was
4 days (interquartile range, 2–7 days) (Supplemental Figure 2).
The most common initial modality was continuous RRT for
24 h/d (52.4%). Other modalities included intermittent he-
modialysis (30.0%), continuous RRT for #12 h/d (14.9%),
and peritoneal dialysis (1.3%). A total of 625 of the 637 pa-
tients (98.1%) with AKI-RRT required invasive mechanical
ventilation, and AKI-RRT developed at a median of 3 days
following intubation (interquartile range, 2–6 days)
(Supplemental Figure 3). Patients who initiated RRT on days
1 and 2 following ICU admission were younger, more likely to
have CKD stages 4 and 5, and more likely to receive invasive
mechanical ventilation on ICU admission compared with pa-
tients who initiated RRTon days 3–14 (Supplemental Table 4).
Across multiple categories of age, sex, race, comorbidities, and
hospital characteristics, patients with AKI-RRT had a higher
28-day mortality than patients without AKI, and patients with
AKI that was not treated with RRT had mortality rates that
were intermediate between AKI-RRT and no AKI (Figure 2).
Predictors of AKI-RRT and RRT/Death
In univariate analyses, we found monotonic relationships be-
tween each of the following characteristics and a higher risk of
AKI-RRT: higher body mass index, higher stages of CKD,
lower PaO2:FiO2 ratio on ICU admission, and greater number
of vasopressors received on ICU admission (Figure 3).
In multivariable analyses, CKD was associated with a
higher risk of AKI-RRT (odds ratio, 5.63; 95% confidence in-
terval [95% CI], 4.03 to 7.86 for CKD stages 4 and 5 compared
with no CKD; odds ratio, 1.62; 95% CI, 1.27 to 2.05 for CKD
stage 3 compared with no CKD). Additional patient-level risk
factors for AKI-RRTwere men, non-White race, hypertension,
diabetes mellitus, higher body mass index, lower PaO2:FiO2
ratio on ICU admission, and D-dimer .2500 ng/ml on ICU
admission (Figure 4). A shorter interval from hospital to ICU
166 JASN
All Patients, n53099 No AKI-RRT, n52462 AKI-RRT, n5637 P Value
126 (85–194) 133 (91–204) 104 (74–104) ,0.001
54 (1.7) 46 (1.9) 8 (1.3) 0.39
619 (20.0) 540 (21.9) 79 (12.4) ,0.001
681 (22.0) 552 (22.4) 129 (20.3) 0.24
1305 (42.1) 981 (39.8) 324 (50.9) ,0.001
admission (#3 versus .3 days) was associated with a lower
risk of AKI-RRT. Patients admitted to hospitals with greater
regional density of COVID-19 had a lower odds of AKI-RRT
(odds ratio, 0.66; 95% CI, 0.47 to 0.93 for highest versus lowest
quartile) (Figure 4). The finding of lower rates of AKI-RRT in
patients admitted to hospitals with greater regional density of
COVID-19 persisted in analyses restricted to patients with
AKI stage 3 (Supplemental Figure 4). Interpretations were
similar in multiple sensitivity analyses (Supplemental Tables
5–8).
Factors associated with AKI-RRT were largely similar to
those associated with the composite of RRT/death but with
several notable exceptions. Whereas age $80 years was asso-
ciated with a lower odds of AKI-RRT, it was associated with a
higher odds of RRT/death (Figure 4). Additionally, whereas
number of ICU beds was not associated with AKI-RRT, pa-
tients admitted to hospitals with fewer ICU beds had a higher
odds of RRT/death (Figure 4). Finally, whereas patients ad-
mitted to hospitals with greater regional density of COVID-19
had a lower odds of AKI-RRT, they had a higher odds of
RRT/death (Figure 4).
Interhospital Variation in AKI-RRT
The incidence of AKI-RRT varied widely between hospitals,
ranging from 7.5% at the lowest-risk hospital to 44.6% at the
highest (Figure 5A). This variation was attenuated in models
adjusted for patient-level characteristics (range, 9.6%–32.7%)
(Figure 5B) and was further attenuated in models adjusted for
both patient- and hospital-level characteristics (range,
12.4%–29.1%) (Figure 5C).
Predictors of 28-Day Mortality among Patients with
AKI-RRT
Among the 637 patients with AKI-RRT, 350 (54.9%) died
within 28 days of ICU admission. Older age, receipt of two
or more vasopressors at the time of RRT initiation, and severe
oliguria (urine output ,100 ml/d) at the time of RRT initia-
tion were each associated with a higher risk of 28-day mortal-
ity, whereas CKD stage 4 or 5 was associated with a lower risk
of 28-day mortality (Figure 6). Patients admitted to hospitals
with fewer ICU beds and to those with greater regional density
of COVID-19 also had a higher risk of 28-day mortality
(Figure 6).
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A 80
B 80
No AKI
70 70
AKI no RRT
60 AKI-RRT 60
28-Day Mortality (%)

28-Day Mortality (%)

50 50

40 40

30 30

20 20

10 10

0 0
18-39 40-49 50-59 60-69 70-79 ≥80 Male Female
Age (years) Sex

C 80 D
80
70 70

60 60
28-Day Mortality (%)

28-Day Mortality (%)

50 50

40 40

30 30

20 20

10 10

0 0
White Non-White Smoking Hypertension Diabetes CAD CHF Malignancy
Race

E F
80 80

70 70

60 60
28-Day Mortality (%)
28-Day Mortality (%)

50 50

40 40

30 30

20 20

10 10

0 0
≥100 50-99 <50 1 2 3 4
Number of ICU beds Regional Density of COVID-19

Figure 2. Patients with AKI-RRT have higher 28-day mortality than patients without AKI-RRT. This figure shows the 28-day mortality of
patients with AKI-RRT, those with AKI who were not treated with RRT, and those without AKI across categories of age (A), sex (B), race
(C), comorbidities (D), and hospital characteristics; number of ICU beds (E) and regional density of COVID-19 (F). CAD, coronary artery
disease; CHF, congestive heart failure.

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AGE (yrs)
HOME MEDICATIONS
9 18-39 15
13 40-49 20 9 Anticoagulant 15

21 50-59 24 37 Statin 23
28 60-69 25 21 Aspirin 23
20 70-79 20 18 ACE-I 24
9 ≥80 9
3 MRA 24

17 ARB 30
SEX
65 Male 23
35 Female 16 PaO2:FiO2 Ratio
36 Not ventilated 13

RACE 11 ≥200 16
37 White 15 28 100–199 22
63 Non-White 24
25 <100 33

BODY MASS INDEX (kg/m2)

17 <25 10 NUMBER OF VASOPRESSORS ON ICU DAY 1
31 25-29.9 19 58 0 17

24 30-34.9 22 32 1 23
13 35-39.9 24 8 2 27
15 ≥40 31
2 ≥3 39

Coexisting Conditions
5 Smoking NUMBER OF ICU BEDS
17
5 Malignancy 20 37 ≥100 20

13 CAD 22 29 50-99 17
60 HTN 24 34 <50 23
9 CHF 26
40 Diabetes 27
REGIONAL DENSITY OF COVID-19
10 1 22
CHRONIC KIDNEY DISEASE
18 2 23
71 No CKD 17
22 CKD 3 24 31 3 19

7 CKD 4 or 5 50 40 4 20

80 60 40 20 0 0 10 20 30 40 50 60 40 20 0 0 10 20 30 40
Frequency (%) AKI-RRT (%) Frequency (%) AKI-RRT (%)

Figure 3. Patient- and hospital-level characteristics and AKI-RRT. The frequency of patient- and hospital-level characteristics in the overall
cohort (n53099) is displayed in blue, and the proportion of patients who developed AKI-RRT within 14 days following ICU admission is
displayed in red. Smoking includes both current and former smoking. ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II
receptor blocker; CAD, coronary artery disease; CHF, congestive heart failure; HTN, hypertension; MRA, mineralocorticoid receptor antagonist.

When 28-day mortality was assessed from the date of RRT
initiation (rather than from ICU admission), 365 patients
(57.3%) had died, and the results were overall similar
(Supplemental Table 9).
We also examined variation in 28-day mortality among pa-
tients with AKI-RRTaccording to geographic region. As shown in
Supplemental Figure 5, unadjusted 28-day mortality was highest
among patients admitted to hospitals in the northeastern part of
the United States. Patients admitted to hospitals in the Northeast
had similar median age and burden of comorbidities compared
with patients admitted elsewhere but had higher rates of receipt of
invasive mechanical ventilation on admission to the ICU. Re-
gional density of COVID-19 was highest in the Northeast.
Renal Recovery
Among the 637 patients with AKI-RRT, during a median
follow-up of 17 days (interquartile range, 9–30 days; range,
1–123 days), 403 patients (63.3%) had died, 216 (33.9%) were
discharged, and 18 (2.8%) were still hospitalized. Among the
216 patients discharged, 73 (33.8%) remained RRT dependent
on discharge. When these 73 patients were followed to 60 days
from ICU admission, 69 (94.5%) were still alive, one (1.4%)

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Variable Odds Ratio (95% CI) for AKI-RRT Odds Ratio (95% CI) for RRT/Death
Age (yrs)
18–39 (REF) 1.00 1.00
40–49 1.24 (0.78-1.95) 1.29 (0.87-1.93)
50–59 1.49 (0.97-2.28) 1.53 (1.05-2.23)
60–69 1.55 (1.01-2.37) 2.29 (1.58-3.32)
70–79 1.22 (0.77-1.93) 2.34 (1.58-3.48)
80 0.48 (0.26-0.88) 3.69 (2.33-5.82)
Male Sex 1.93 (1.54-2.40) 1.80 (1.49-2.16)
Non–White Race 1.74 (1.41-2.15) 1.56 (1.30-1.86)
Hypertension 1.33 (1.05-1.68) 1.21 (0.99-1.47)
Diabetes Mellitus 1.63 (1.33-2.01) 1.40 (1.17-1.67)
Body Mass Index (kg/m2)
<25 (REF) 1.00 1.00
25–29.9 1.70 (1.19-2.45) 1.44 (1.09-1.89)
30–34.9 2.04 (1.41-2.96) 1.45 (1.09-1.94)
35–39.9 2.43 (1.61-3.66) 2.40 (1.72-3.36)
40 3.15 (2.10-4.72) 2.88 (1.06-4.04)
Chronic Kidney Disease
No CKD (eGFR 60 ml/min/1.73m2) (REF) 1.00 1.00
CKD stage III (eGFR 30-59 ml/min/1.73m2) 1.62 (1.27-2.05) 1.86 (1.51-2.28)
CKD stages IV and V (eGFR <30 ml/min/1.73m2) 5.63 (4.03-7.86) 4.72 (3.34-6.69)
Coronary Artery Disease 0.91 (0.67-1.24) 1.17 (0.90-1.51)
Congestive Heart Failure 1.28 (0.91-1.80) 1.37 (1.01-1.85)
Active Malignancy 1.13 (0.72-1.76) 1.53 (1.05-2.23)
3 Days from Hospital to ICU Admission 0.79 (0.63-0.98) 0.87 (0.72-1.05)
Lymphocyte Count <1,000/mm3 on ICU Day 1 1.09 (0.86-1.38) 1.03 (0.84-1.66)
PaO2:FiO2
Not receiving mechanical ventilation (REF) 1.00 1.00
Mechanically ventilated, PaO2:FiO2 200 1.23 (0.84-1.80) 1.04 (0.76-1.43)
Mechanically ventilated, PaO2:FiO2 100–199 1.94 (1.47-2.54) 1.88 (1.50-2.36)
Mechanically ventilated, PaO2:FiO2 <100 3.11 (2.37-4.08) 3.37 (2.67-4.26)
Shock 1.06 (0.78-1.42) 1.42 (1.08-1.87)
Altered Mental Status, ICU Day 1 0.68 (0.52-0.87) 1.21 (0.98-1.49)
Secondary Infection, ICU Day 1 1.05 (0.83-1.33) 1.25 (1.02-1.54)
Coagulation Component of SOFA Score
0 (REF) 1.00 1.00
1 1.18 (0.91-1.55) 1.33 (1.05-1.67)
2-4 1.39 (0.92-2.12) 2.05 (1.43-2.94)
Liver Component of SOFA Score
0 (REF) 1.00 1.00
1 1.00 (0.60-1.64) 1.04 (0.78-1.39)
2-4 1.17 (0.85-1.62) 1.26 (0.82-1.94)
D-dimer (ng/ml)
<1000 (REF) 1.00 1.00
1000-2500 1.12 (0.80-1.56) 1.16 (0.88-1.53)
>2500 1.82 (1.34-2.47) 2.02 (1.55-2.63)
Hospital Size (no. pre-COVID ICU beds)
Large (100 ICU beds) (REF) 1.00 1.00
Medium (50–99 ICU beds) 0.82 (0.63-1.07) 1.11 (0.88-1.39)
Small (<50 ICU beds) 1.12 (0.86-1.44) 2.02 (1.62-2.53)
Regional Density of COVID-19 (quartiles)
1 (REF) 1.00 1.00
2 0.95 (0.65-1.37) 1.29 (0.92-1.80)
3 0.68 (0.48-0.97) 1.08 (0.79-1.47)
4 0.66 (0.47-0.93) 1.51 (1.12-2.04)

0.25 0.5 1 2 4 8 0.25 0.5 1 2 4 8

Figure 4. Multivariable model for AKI-RRT and RRT/death. This figure shows (left panel) the odds of AKI-RRT and (right panel) the composite
of AKI-RRT or death (RRT/death) within 14 days following ICU admission according to patient- and hospital-level characteristics. A total of 637
of 3099 patients (20.6%) developed AKI-RRT. A total of 1205 of 3099 patients (38.9%) developed RRT/death, of whom 413 (34.3%) developed
AKI-RRT and did not die, 568 (47.1%) died without AKI-RRT, and 224 (18.6%) both developed AKI-RRT and died. Unless otherwise indicated,
severity of illness covariates were selected as the worst value on ICU day 1 or 2. SOFA, Sequential Organ Failure Assessment.

had died, and three (4.1%) had unknown survival status. Of
the 69 patients still alive at day 60, 39 (56.5%) remained RRT
dependent at day 60, 24 (34.8%) became independent of RRT
by day 60, and six (8.7%) had unknown RRT dependence data
on day 60 (Figure 1).
AKI Not Treated with RRT
The incidence, severity, and outcomes of AKI not treated with
RRT, both on hospital admission and within 14 days following
ICU admission, are shown in Supplemental Figures 6 and 7
and Supplemental Table 10. The cumulative incidence of AKI
by stage at days 3, 7, and 14 is shown in Figure 7.
DISCUSSION
In this multicenter cohort study of over 3000 critically ill
adults with COVID-19 admitted to ICUs at 67 hospitals across
the United States, we found that over one in five patients de-
veloped AKI-RRT. CKD, higher body mass index, and greater
severity of hypoxemia on ICU admission are each indepen-
dently associated with a higher risk of AKI-RRT. Among
patients with AKI-RRT, 63% died during hospitalization.
Predictors of death in patients with AKI-RRT include older
age, oliguria, and admission to a hospital with fewer ICU
beds or one with greater regional density of COVID-19. Fi-
nally, among patients with AKI-RRT who survived to hospi-
tal discharge, 34% remained RRT dependent on discharge.
Cumulatively, these findings indicate that AKI-RRT is com-
mon among critically ill patients with COVID-19 and that it
is associated with high acute mortality and high rates of
continued RRT dependence among survivors.
Several studies have examined the incidence of AKI in hos-
pitalized patients with COVID-19,3–5 but few have focused on
AKI-RRT. The United Kingdom–based Intensive Care Na-
tional Audit and Research Centre found that among 10,168

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A Unadjusted critically ill patients with COVID-19, 26.6% developed AKI-

RRT,26 similar to the 21% that we report here.
100
We identified several patient-level risk factors for AKI-RRT,
including CKD, higher body mass index, men, non-White race,
Proportion (%) with AKI-RRT

80 diabetes mellitus, and hypertension. CKD and obesity have each

been associated with a higher risk of AKI in patients with H1N1
60 influenza27–29 and in critically ill patients in non–COVID-19
settings.30 CKD is a well-known risk factor for AKI in gen-
40 eral,31,32 and a recent study in hospitalized patients with
COVID-19 in New Orleans found that patients with AKI-RRT
had a higher median body mass index compared with patients
20
without AKI-RRT.10 We also found that lower PaO2:FiO2 ratio
and shock on ICU admission are each independent risk factors
0 for AKI-RRT. Similar to Hirsch et al.,5 we found that AKI-RRT
0 10 20 30 40 50 60 commonly occurs around the time of intubation, suggesting a
role for alterations in hemodynamics as a potentially important
B Adjusted for Patient Characteristics mechanism for AKI in COVID-19 because vasopressors are of-
100 ten initiated at the time of intubation.
We found that older age is associated with a lower risk of AKI-
RRT but a higher risk of RRT/death. It is possible that informed
Proportion (%) with AKI-RRT

80
decision making about poor outcomes among older patients
with AKI-RRT in non–COVID-19 settings may have led to the
60 decision to not initiate RRT in patients $80 years of age.33,34
We found that admission to a hospital with greater regional
40 density of COVID-19 is associated with a lower risk of AKI-
RRT but a higher risk of RRT/death. Multiple potential expla-
nations could account for this finding. Patients admitted to
20
hospitals with greater regional density of COVID-19 may have
presented at a more advanced stage of acute illness or may have
0 differed from patients admitted to hospitals with less regional
0 10 20 30 40 50 60 density of COVID-19 in other ways that were not captured by
our data. Variation in the risk- and reliability-adjusted use of
C Adjusted for Patient and Hospital Characteristics RRT in critically ill patients has been described in settings
100 outside of COVID-19,35 consistent with heterogeneity in se-
verity of illness and in patient and provider preferences. Be-
Proportion (%) with AKI-RRT

cause we did not capture data on the reasons for RRT initiation
80
or noninitiation, including data on goals of care as well as the
availability of RRTequipment, nurses, and physicians, caution
60 is needed in interpreting our findings.
We also identified several patient- and hospital-level risk
40 factors for death among patients with AKI-RRT. Patient-level
risk factors included older age and severe oliguria, whereas
20 hospital-level risk factors included greater regional density
of COVID-19 and fewer ICU beds. Both older age and oliguria
have been associated with death in patients with AKI-RRT in
0
non–COVID-19 settings.25 Although CKD was a predictor of
0 10 20 30 40 50 60 AKI-RRT, we found that CKD was inversely associated with
Hospital Rank by Treatment
28-day mortality among patients with AKI-RRT. One possible
Figure 5. The incidence of AKI-RRT varies by hospital. Inter- explanation for these findings is that patients with relatively
hospital variation in AKI-RRT. Risk- and reliability-adjusted rates intact baseline kidney function would have required a larger
of AKI-RRT within 14 days following ICU admission. (A) is un- insult to develop AKI-RRT, and may therefore have been
adjusted. (B) is adjusted for patient-level characteristics. (C) is sicker, than patients with advanced underlying CKD.
adjusted for both patient- and hospital-level characteristics, in- The finding that mortality differed considerably according
cluding number of ICU beds and regional density of COVID-19. to number of ICU beds is intriguing. It is well known that ICU
organization, experience, and staffing may affect outcomes in

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Variable Odds Ratio (95% CI) for 28 -Day Forest Plot

Mortality
Age (yrs)
18–39 (REF) 1.00
40–49 1.17 (0.47-2.89)
50–59 1.13 (0.49-2.60)
60–69 2.16 (0.93-5.03)
70–79 2.86 (1.15-7.15)
≥80 4.73 (1.24-18.10)
Male Sex 1.29 (0.83-2.00)
Non–White Race 1.05 (0.68-1.62)
Hypertension 1.09 (0.69-1.74)
Diabetes Mellitus 1.00 (0.66-1.49)
Body mass index (kg/m2)
<25 (REF) 1.00
25–29.9 1.26 (0.60-2.65)
30–34.9 1.25 (0.58-2.70)
35–39.9 0.92 (0.40-2.11)
≥40 1.63 (0.73-3.62)
Chronic Kidney Disease
No CKD (eGFR ≥60 ml/min/1.73m2) (REF) 1.00
CKD stage III (eGFR 30-59 ml/min/1.73m2) 0.90 (0.57-1.43)
CKD stages IV, V (eGFR <30 ml/min/1.73m2) 0.48 (0.28-0.83)
Coronary Artery Disease 1.17 (0.65-2.13)
Congestive Heart Failure 1.50 (0.79-2.84)
Active Malignancy 2.56 (0.96-6.82)
≤3 Days from Hosp to ICU Admission 0.91 (0.60-1.38)
Lymphocyte Count <1,000 mm3 0.90 (0.55-1.45)
PaO2:FiO2
Not receiving mechanical ventilation (REF) 1.00
Mechanically ventilated, PaO2:FiO2 ≥200 0.69 (0.37-1.29)
Mechanically ventilated, PaO2:FiO2 100–199 0.89 (0.51-1.53)
Mechanically ventilated, PaO2:FiO2 <100 1.63 (0.87-3.07)
Altered Mental Status, ICU Day 1 1.56 (0.95-2.55)
Secondary Infection, ICU Day 1 0.80 (0.50-1.26)
Vasopressors
0 (REF) 1.00
1 1.40 (0.87-2.25)
≥2 2.27 (1.30-3.95)
Coagulation Component of SOFA Score
0 (REF) 1.00
1 1.42 (0.75-2.68)
2-4 2.28 (0.88-5.94)
Liver Component of SOFA Score
0 (REF) 1.00
1 0.92 (0.49-1.73)
2-4 1.30 (0.64-2.64)
Urine Output (ml/day)
>500 (REF) 1.00
100–500 1.14 (0.70-1.83)
<100 2.14 (1.27-3.61)
Initial RRT modality
Intermittent Hemodialysis (REF) 1.00
CRRT for 12–24 hours/day 1.36 (0.83-2.23)
Hospital Size (no. pre-COVID ICU beds)
Large (≥100 ICU beds) (REF) 1.00
Medium (50–99 ICU beds) 3.67 (2.20-6.13)
Small (<50 ICU beds) 6.89 (4.05-11.72)
Regional Density of COVID-19 (quartiles)
1 (REF) 1.00
2 1.73 (0.84-3.55)
3 1.22 (0.61-2.41)
4 2.11 (1.04-4.27)
0.25 0.5 1 2 4 8 16

Figure 6. Multivariable model for 28-day mortality in patients with AKI-RRT. Unless otherwise indicated, severity of illness covariates
were selected on the day of RRT initiation or if unavailable, the day prior. CRRT, continuous RRT; SOFA, Sequential Organ Failure
Assessment.

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 CLINICAL RESEARCH www.jasn.org
Day 3
100%
90%
80%
70%
Incidence 60%
50%
40%
30%
20%
10%
0%
No AKI Stage 1
Figure 7. Incidence of AKI at 3, 7, and 14 days from ICU admission. For each time period, patients were categorized according to the
highest stage of AKI achieved.
critically ill patients in non–COVID-19 settings. For example,
studies have demonstrated the beneficial effects of being ad-
mitted to an ICU with mandatory staffing (or consultation) by
intensivists.36 The importance of experience is highlighted by
studies revealing a “volume-outcome relationship” for me-
chanically ventilated patients 37 and patients receiving
RRT,38–40 where patients who receive these interventions
have better outcomes if admitted to hospitals that care for a
larger number of such patients.
When analyzing rates of renal recovery among patients
with AKI-RRT who survived to hospital discharge, we found
that .30% remained RRT dependent on discharge. Although
this number decreased considerably when patients were fol-
lowed to day 60, studies of AKI-RRT in critically ill patients
without COVID-19 have generally found lower rates of RRT
dependence at hospital discharge among survivors, ranging
from 7% to 18% in most studies.12,41,42 Potential reasons for
the high rate of persistent RRT dependence in COVID-19 in-
clude severe or ongoing renal tubular injury due to direct viral
invasion7,9 and cytokine storm.8 Further studies are needed to
determine long-term renal outcomes in these patients.
Our study has several strengths. First, the large number of
patients in our cohort allowed us to focus on AKI-RRT, the
most severe and clinically relevant form of AKI. Second, we
included patients from 67 geographically diverse sites across
the United States, thereby increasing the generalizability of our
findings and allowing us to examine interhospital variability in
outcomes. Third, all data were obtained by detailed chart re-
view rather than reliance on administrative or billing codes,
which allowed us to capture granular and reliable data. Fourth,
over 97% of the patients with AKI-RRT had a definitive out-
come (dead or discharged) by the end of follow-up.
We also acknowledge several limitations. First, data on AKI-
RRT were only captured for the first 14 days following ICU
admission. Accordingly, we may have underestimated the true
incidence of AKI-RRT in critically ill patients with COVID-19,
although rates of AKI-RRT declined precipitously over time,
with 80% of the known cases occurring in the first 7 days of
172 JASN
Day 7 Day 14
Stage 2 Stage 3 RRT
ICU admission (Supplemental Figure 2). Second, data on SCr
prior to hospitalization were missing for a large proportion of
the cohort. In these patients, we used SCr on hospital admission
as a surrogate for baseline SCr, which may have overestimated
the prevalence of CKD in our cohort. Third, we did not collect
data on urinalysis/urine sediment or volume status at the time of
RRT initiation or during the course of RRT. Fourth, the majority
of cases of AKI-RRT were from the Northeast and Midwest re-
gions of the United States, reflecting the regional surge in
COVID-19 cases in March and April 2020, and we did not in-
clude data from international sites. Thus, our findings may not
be generalizable beyond the United States or to regions of the
United States that were not well-represented in this study. Fifth,
as with all observational studies, there may be residual con-
founding, which may have particularly affected our findings
with respect to hospital-level characteristics and outcomes. For
example, our models may not sufficiently account for resource
availability across hospitals, as we did not capture data on hos-
pital or ICU patient volume or the availability of RRT machines,
physicians, and nurses. Sixth, we did not determine the reasons
for RRT initiation and noninitiation.
In this multicenter, nationally representative cohort study
of critically ill adults with COVID-19 in the United States, we
found that more than one in five patients developed AKI-RRT,
over 60% of whom died within 28 days. Among those with
AKI-RRT who survived to hospital discharge, nearly one in
three remained RRT dependent. We identified several patient-
and hospital-level risk factors for AKI-RRT and death. Future
studies are needed to investigate the long-term outcomes of
patients with AKI-RRT in the setting of COVID-19, as well as
to explore the underlying etiologies of AKI in this setting so
that targeted therapies can be developed.
DISCLOSURES
The authors of the writing committee are supported by National Institutes of
Health (NIH) grants F32HL149337 (to A. Admon), R01AG066471 (to L. Chan),
JASN 32: 161–176, 2021

U01DK106962 (to S. Coca), R01DK115562 (to S. Coca), R01HL85757 (to
S. Coca), R01DK112258 (to S. Coca), U01OH011326 (to S. Coca),
R01DK126477 (to S. Coca), F32DC17342 (to S. Gupta), R01HL144566 (to
D. Leaf ), R01DK125786 (to D. Leaf ), UL1TR001998 (to J. Neyra),
R01HL085757 (to C. Parikh), and K23DK120811 (to A. Srivastava). L. Chan
reports grants from NIH and Renal Research Institute, outside the submitted
work. D. Charytan reports personal fees from AstraZeneca, Douglas and London,
Fresenius, GSK, Merck, PLC Medical, and Zoll; grants from BioPorto; grants and
personal fees from Amgen, Medtronic, Gilead, and NovoNordisk; personal fees
and other from Jannssen; and other from Daichi-Sankyo, outside the submitted
work. M. Christov is currently employed by New York Medical College, Regen-
eron Pharmaceuticals; and reports ownership interest in Regeneron Pharmaceu-
ticals. S. Coca is a cofounder and a member of the advisory board of RenalytixAI,
and owns equity in the same. In the past 3 years, he has received consulting fees
from Bayer, Boehringer-Ingelheim, CHF Solutions, pulseData, Quark Bio-
pharma, Relypsa, RenalytixAI, and Takeda Pharmaceuticals as well as personal
fees from inRegen. J. Flythe reports other from American Renal Associates, the
American Society of Nephrology, AstraZeneca, Fresenius Medical Care, North
America, the National Kidney Foundation, and NxStage Medical; and grants from
Renal Research Institute and Fresenius Medical Care, outside the submitted work.
A. Friedman is currently a member of the scientific advisory board for GI
Dynamics and has consulted for DSMB Watermark. S. Gupta is a scientific co-
ordinator for the Anaemia Studies in CKD: Erythropoiesis via a Novel PHI Dap-
rodustat (ASCEND) trial (GlaxoSmithKline); and reports personal fees from
GlaxoSmithKline and grants from NIH, outside the submitted work. S. Hayek
is funded by National Heart, Lung, and Blood Institute (NHLBI) grant
1R01HL153384-01; the Frankel Cardiovascular Center COVID-19: Impact Re-
search Ignitor (U-M G024231) award; and reports personal fees from Trisaq,
outside the submitted work. S. Hedayati reports honoraria from the American
College of Physicians for participation in Nephrology Medical Knowledge Self-
Assessment Program (MKSAP) and the American Society of Nephrology Post-
Graduate Education Program; is a scientific advisor for or reports membership in
the American Heart Association; and reports study sections in American College
of Physicians (ACP), MKSAP Nephrology Committee and the American Society
of Nephrology In-Training Examination Committee. D. Leaf received research
support from BioPorto. K. Liu reports grants from NIH: NHLBI and NIH: Na-
tional Institute of Diabetes and Digestive and Kidney Disease (NIDDK); personal
fees from the American Thoracic Society, Astra Zeneca, Baxter, Biomerieux,
Durect, Potrero Med, Quark, Theravance, and UpToDate; and other from Amgen
and the National Policy Forum on Critical Care and ARF, outside the submitted
work. M. Melamed reports personal fees from the American Board of Internal
Medicine and Icon Medical Consulting, outside the submitted work. M. Molnar
reports personal fees from Abbvie, CareDx, and Natera; and grants from CareDx
and Viracor, outside the submitted work. J. Neyra consults for Baxter Health-
ercare, Inc. and Renibus Therapeutics, Inc. C. Parikh serves on the board of
Renalytix and is a Data Safety Monitoring Board (DSMB) member for Genfit.
C. Parikh reports consultancy agreements with Genfit Biopharmaceutical Com-
pany; ownership interest in Renaltix AI; research funding from NHLBI and
NIDDK; and scientific advisor for or membership in Genfit Biopharmaceutical
Company and Renalytix. C. Schulze is a medical director for Davita-Century City
home hemodialysis program. M. Sise receives research funding from Abbvie,
Gilead, MEDSerono, and Merck; honoraria from the International Society of
Hemodialysis–Hemodialysis University Lecture; consults for BioPorto; and serves
on the scientific advisory board for Abbvie and Gilead. A. Srivastava received
grants from NIH/NIDDK and personal fees from Horizon Pharma, Public Lim-
ited Company, AstraZeneca, and CVS Caremark. J. Velez is currently employed by
Ochsner Clinic Foundation; reports consultancy agreements with Mallinckrodt
Pharmaceuticals; reports honoraria from Mallinckrodt Pharmaceuticals and Ot-
suka; is a scientific advisor for or reports membership in Mallinckrodt Advisory
Board and Retrophin Advisory Board; and speakers bureau: Otsuka Pharmaceu-
ticals. A. Vijayan reports consultancy agreements with Boehringer Ingelheim,
NxStage, and Sanofi; reports research funding from Astellas; reports spectral
honoraria from Astute and Sanofi; is a scientific advisor for or reports member-
ship in NxStage; and is a member of the National Kidney Foundation. All re-
maining authors have nothing to disclose.
JASN 32: 161–176, 2021
www.jasn.org CLINICAL RESEARCH
FUNDING
None.
ACKNOWLEDGMENTS
A. Bansal, S. Brenner, L. Chan, D. Charytan, S. Coca, R. Dy, J. Flythe,
A. Friedman, N. Goyal, S. Hayek, S. Hedayati, M. Joo, E. Judd, O. Kamal,
A. Leonberg-Yoo, K. Liu, M. Mallappallil, M. Melamed, J. Neyra, H. Nguyen,
S. Puri, A. Rashidi, R. Redfern, E. Schenck, C. Schulze, S. Sharma, A. Shehata,
M. Sosa, A. Srivastava, A. Sutherland, J. Velez, A. Vijayan, and J. Zhang
collected data; A. Admon, J. Boateng, S. Gupta, D. Leaf, C. Parikh, S. Short,
and M. Sise analyzed data; S. Gupta and D. Leaf interpreted the results and
wrote the manuscript; all authors contributed to revision of the final version
of the manuscript, approved the final version submitted, and agree to be
accountable for all aspects of the work in ensuring that questions related to
the accuracy or integrity of any part of the work are appropriately investigated
and resolved; D. Leaf acts as guarantor for the work; and D. Leaf attests
that all listed authors meet authorship criteria and that no others meeting the
criteria have been omitted.
SUPPLEMENTAL MATERIAL
This article contains the following supplemental material online at http://
jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2020060897/-/
DCSupplemental.
Supplemental Material. List of the STOP-COVID Investigators and their
affiliations.
Supplemental Figure 1. Number of patients with AKI-RRT by state among
contributing sites.
Supplemental Figure 2. Time to AKI-RRT.
Supplemental Figure 3. Timing of AKI-RRT in relation to intubation.
Supplemental Figure 4. Proportion of patients with AKI stage 3 treated with
RRT by quartile of regional density of COVID-19.
Supplemental Figure 5. The 28-day mortality of patients with AKI-RRT by
region.
Supplemental Figure 6. AKI on hospital admission and within 14 days fol-
lowing ICU admission.
Supplemental Figure 7. Flowchart of outcomes of patients without AKI-
RRT.
Supplemental Table 1. List of participating sites.
Supplemental Table 2. Definitions of baseline characteristics, comorbidi-
ties, treatments, and outcomes.
Supplemental Table 3. Complete list of patient characteristics according to
AKI stage.
Supplemental Table 4. Characteristics of patients with AKI-RRT on days 1
and 2 versus days 3–14.
Supplemental Table 5. Multivariable model for AKI-RRT, accounting for
clustering.
Supplemental Table 6. Multivariable model for AKI-RRT among patients
with a prehospital baseline serum creatinine available.
Supplemental Table 7. Multivariable model for AKI-RRTexcluding patients
transferred from an outside hospital.
Supplemental Table 8. Multivariable model for AKI-RRT among patients
who survived 14 days.
Supplemental Table 9. Multivariable model for 28-day mortality from the
day of RRT initiation.
Supplemental Table 10. AKI by stage and 28-day mortality among patients
with a prehospital baseline SCr available.
AKI-RRT in COVID-19 173
 CLINICAL RESEARCH www.jasn.org
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AFFILIATIONS

1
Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
2
Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
3
Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York
4
Department of Internal Medicine, Hackensack Meridian School of Medicine, Seton Hall, Nutley, New Jersey
5
Department of Internal Medicine, Heart and Vascular Hospital, Hackensack Meridian Health Hackensack University Medical Center,
Hackensack, New Jersey
6
Division of Cardiology, University of Michigan Medical Center, Ann Arbor, Michigan
7
Division of Pulmonary and Critical Care Medicine, Rutgers New Jersey Medical School, Newark, New Jersey
8
Division of Nephrology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
9
Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine,
Northwestern University Feinberg School of Medicine, Chicago, Illinois
10
Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
11
Department of Medicine, Hackensack Meridian Health Mountainside Medical Center, Glen Ridge, New Jersey
12
Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina
School of Medicine, Chapel Hill, North Carolina
13
Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, North Carolina
14
Division of Nephrology and Hypertension, University Hospitals Cleveland Medical Center, Cleveland, Ohio
15
Divison of Pulmonary and Critical Care Medicine, Department of Medicine Weill Cornell Medicine, New York, New York
16
Division of Nephrology, Tufts Medical Center, Boston, Massachusetts
17
Division of Nephrology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
18
Division of Pulmonary and Critical Care Medicine, University Medical Center, University of Nevada, Las Vegas, Nevada
19
Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado
20
Division of Nephrology, Cook County Health, Chicago, Illinois
21
Division of Pulmonary, Critical Care, Hyperbaric, Allergy, and Sleep Medicine, Loma Linda University Health, Loma Linda, California
22
Division of Nephrology, Washington University, St. Louis, Missouri
23
Division of Nephrology, New York University Grossman School of Medicine, New York, New York
24
Division of Nephrology, Department of Medicine, University of California, Los Angeles, California
25
Department of Medicine, Section of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois, Chicago, Illinois
26
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana
27
Division of Nephrology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
28
Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine and Jackson Memorial Hospital, Miami,
Florida
29
Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama
30
Department of Nephrology, Ochsner Health System, New Orleans, Louisiana
31
Ochsner Clinical School, The University of Queensland, Brisbane, Queensland, Australia
32
Division of Nephrology, Kings County Hospital Center, New York City Health and Hospital Corporation, Brooklyn, New York
33
Research Department, ProMedica Research, ProMedica Toledo Hospital, Toledo, Ohio
34
Renal and Electrolyte Division, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
35
Division of Nephrology, Department of Internal Medicine, Bone and Mineral Metabolism, University of Kentucky, Lexington, Kentucky
36
Division of Nephrology and Critical Care Medicine, University of California, San Francisco, California
37
Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia
38
Department of Medicine-Nephrology, Westchester Medical Center, New York Medical College, New York, New York
39
Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
40
Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts

JASN 32: 161–176, 2021 AKI-RRT in COVID-19 175

 CLINICAL RESEARCH www.jasn.org

41
University of Vermont Larner College of Medicine, Burlington, Vermont
42
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
43
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
44
Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
45
Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts
46
Division of Nephrology, Johns Hopkins School of Medicine, Baltimore, Maryland

176 JASN JASN 32: 161–176, 2021