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Acute kidney injury in patients hospitalized with COVID-19

2020; Elsevier BV; Volume: 98; Issue: 1 Linguagem: Inglês

10.1016/j.kint.2020.05.006

1523-1755

Jamie S. Hirsch, Jia Hwei Ng, Daniel W. Ross, Purva Sharma, Hitesh H. Shah, Richard Barnett, Azzour D. Hazzan, Steven Fishbane, Kenar D. Jhaveri, Mersema Abate, Hugo Paz Andrade, Richard Barnett, Alessandro Bellucci, Madhu Bhaskaran, Antonio Corona, Bessy Flores Chang, Mark Finger, Steven Fishbane, Michael Gitman, Candice Halinski, Shamir Hasan, Azzour D. Hazzan, Jamie S. Hirsch, Susana Hong, Kenar D. Jhaveri, Yuriy Khanin, Aireen Kuan, Varun Madireddy, Deepa A. Malieckal, Abdulrahman Muzib, Gayatri Nair, Vinay Nair, Jia Hwei Ng, Rushang Parikh, Daniel W. Ross, Vipulbhai Sakhiya, Mala Sachdeva, Richard P. Schwarz, Hitesh H. Shah, Purva Sharma, Pravin C. Singhal, Nupur N. Uppal, Rimda Wanchoo, Bessy Suyin Flores Chang, Jia Hwei Ng,

COVID-19 Clinical Research Studies

The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis. The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis. Since late 2019, when the severe acute respiratory coronavirus 2, and the resulting illness, acute respiratory syndrome with coronavirus 2 (coronavirus disease 2019 [COVID-19]), developed in Wuhan, China,1World Health OrganizationNovel coronavirus—China. January 2020.https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/Date accessed: April 19, 2020Google Scholar COVID-19 has become a worldwide pandemic, with 2.3 million cases reported as of April 19, 2020.2COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University.https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6Date accessed: April 19, 2020Google Scholar In late January 2020, the United States had its first COVID-19 case in Washington state,3Holshue M.L. DeBolt C. Lindquist S. et al.First case of 2019 novel coronavirus in the United States.N Engl J Med. 2020; 382: 929-936Crossref PubMed Scopus (4317) Google Scholar followed by massive growth of infections in New York, the current epicenter.2COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University.https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6Date accessed: April 19, 2020Google Scholar,4CDC COVID-19 Response TeamGeographic differences in COVID-19 cases, deaths, and incidence—United States, February 12–April 7, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 465-471Crossref PubMed Scopus (1) Google Scholar As had been observed in China and Italy, the disease resulted in a large number of hospitalizations, respiratory failure, and intensive care unit (ICU) admissions.5Bhatraju P.K. Ghassemieh B.J. Nichols M. et al.Covid-19 in critically ill patients in the Seattle region—case series.N Engl J Med. 2020; 382: 2012-2022Crossref PubMed Scopus (1833) Google Scholar,6CDC COVID-19 Response TeamSevere outcomes among patients with coronavirus disease 2019 (COVID-19)—United States, February 12–March 16, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 343-346Crossref PubMed Scopus (1568) Google Scholar The New York metropolitan area began to see a rapid increase in COVID-19 cases in February 2020. Our health system, with 23 hospitals in counties in and around New York City, rapidly experienced a surge in COVID-19 hospitalizations, with over 9000 at the time of this writing. As we cared for patients with COVID-19, we noticed an alarming number of patients who developed acute kidney injury (AKI), at rates higher than had been reported from China. Early reports from China and Italy found the rate of AKI to range widely from 0.5% to 29%, with most estimates on the lower end.7Guan W.-J. Ni Z.-Y. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (20519) Google Scholar, 8Wang D. Hu B. Hu C. et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (16387) Google Scholar, 9Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar, 10Chen N. Zhou M. Dong X. et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020; 395: 507-513Abstract Full Text Full Text PDF PubMed Scopus (14520) Google Scholar, 11Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [preprint]. medRxiv. https://doi.org/10.1101/2020.03.04.20031120. Accessed April 19, 2020.Google Scholar, 12Zhou F. Yu T. Du R. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (18962) Google Scholar, 13Cheng Y. Luo R. Wang K. et al.Kidney disease is associated with in-hospital death of patients with COVID-19.Kidney Int. 2020; 97: 829-838Abstract Full Text Full Text PDF PubMed Scopus (1932) Google Scholar, 14Chen T. Wu D. Chen H. et al.Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study.BMJ. 2020; 368: m1091Crossref PubMed Scopus (2799) Google Scholar, 15Yang X. Yu Y. Xu J. et al.Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; 8: 475-481Abstract Full Text Full Text PDF PubMed Scopus (7052) Google Scholar U.S. data has been limited to critically ill patients in the ICU in a Seattle hospital showing a 19% rate of AKI.16Arentz M. Yim E. Klaff L. et al.Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state.JAMA. 2020; 323: 1612-1614Crossref PubMed Scopus (1635) Google Scholar Differences may have resulted from definitions of AKI and the populations studied. Little to date has been published on AKI in COVID-19 beyond rate; for example, wider descriptions of the timing, urine studies, relationship to respiratory failure, detailed analysis of renal replacement therapy (RRT) requirements, risk factors, and outcomes post-AKI are lacking. Northwell Health is uniquely situated to study COVID-19 based on its location in metropolitan New York and because it has 23 hospitals, with a combination of urban and suburban areas and academic tertiary and community hospitals. In this study, we sought to define the rate of AKI among patients hospitalized with COVID-19 and to describe various aspects of the phenomenology of AKI in this patient population. From March 1, 2020, to April 5, 2020, 6477 patients were admitted to 13 Northwell Health hospitals with a diagnosis of COVID-19 present on admission or made during the hospitalization. Of these, 5449 were used as the analysis cohort (Figure 1). The baseline characteristics of patients at hospital admission are provided in Table 1. A total of 1190 patients (21.8%) were treated with mechanical ventilation at some point during the hospitalization. Among the 5449 patients, 888 (16.3%) died, 3280 (60.2%) were discharged to home or to a rehabilitation facility, and 1281 (23.5%) were still in treatment.Table 1Clinical characteristics of the study cohortVariablesOverall (n = 5449)Age (yr)64.0 (52.0, 75.0)Male3317 (60.9)Race Asian466 (8.6) Black1123 (20.6) White2112 (38.8) Declined32 (0.6) Other/multiracial1494 (27.4) Other/unknown222 (4.1)Ethnicity Hispanic/Latino1145 (21.0) Not Hispanic/Latino3953 (72.5) Other/unknown351 (6.4)Language English4433 (81.4) Spanish640 (11.7) Other376 (6.9)Insurance status Commercial1856 (34.1) Medicaid1141 (20.9) Medicare2292 (42.1) Self-pay114 (2.1) Other46 (0.8)Hospital type Tertiary3765 (69.1) Community1684 (30.9)Comorbid conditionsaChronic kidney disease was not included as a comorbid condition because prehospitalization estimated glomerular filtration rate was available only in 15% of patients. HTN3037 (55.7) CAD600 (11.0) HF349 (6.4) PVD98 (1.8) Diabetes1797 (33.0) HIV35 (0.6) Chronic liver disease114 (2.1) COPD296 (5.4) Asthma460 (8.4) OSA164 (3.0) Cancer327 (6.0) Obesity1475 (27.1) Morbid obesity456 (8.4) BMI (kg/m2)28.6 (25.4, 33.1)Admission SCr (mg/dl)1.01 (0.80, 1.34)Medications No. of medications4 (1, 8) ACE-I654 (13.3) ARB902 (18.3)ICU1395 (25.6)Mechanical ventilator1190 (21.8)ECMO10 (0.2)InotropesbInotropes include dobutamine and milrinone.54 (1.0)VasopressorcVasopressors include norepinephrine, epinephrine, vasopressin, dopamine, and angiotensin-2 infusion.1168 (21.4)CCI4 (2, 6)Length of stay (d) Discharged/expired5.7 (3.3, 8.7) Currently hospitalized12.0 (9.3, 16.0)Disposition Discharged3280 (60.2) Expired888 (16.3) Currently admitted1281 (23.5)ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; CAD, coronary artery disease; CCI, Charleson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; HF, heart failure; HTN, hypertension; ICU, intensive care unit; OSA, obstructive sleep apnea; PVD, peripheral vascular disease; SCr, serum creatinine.Values are median (interquartile range) or n (%).a Chronic kidney disease was not included as a comorbid condition because prehospitalization estimated glomerular filtration rate was available only in 15% of patients.b Inotropes include dobutamine and milrinone.c Vasopressors include norepinephrine, epinephrine, vasopressin, dopamine, and angiotensin-2 infusion. Open table in a new tab ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; CAD, coronary artery disease; CCI, Charleson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; HF, heart failure; HTN, hypertension; ICU, intensive care unit; OSA, obstructive sleep apnea; PVD, peripheral vascular disease; SCr, serum creatinine. Values are median (interquartile range) or n (%). Overall, 1993 of 5449 patients (36.6%) developed AKI during their hospitalization. The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4%, and stage 3 in 31.1% (Table 2). The baseline laboratory data of patients are shown in Supplementary Table S1. The timing of initial development of AKI with respect to hospital admission is displayed in Figure 2. Most cases developed early in the course, with 37.3% either arriving with AKI or developing it within 24 hours of admission. The number of patients requiring dialytic support at some point was 285 (overall 5.2% of all patients, representing 14.3% of those with AKI). The modality utilized was intermittent hemodialysis only in 154 patients (54% of all patients requiring RRT), continuous RRT only in 70 (24.6%) and requirement of both treatments at some point in 61 (21.4%). The median time of initiation of dialytic support from hospital admission was 2.0 (interquartile range [IQR]: −1.63, 141) hours. The median number of hours from AKI diagnosis to initiation of dialysis was 0.0 (IQR: 0.0, 79.6).Table 2Baseline characteristics of study cohort, by AKI statusVariablesNo AKI (n = 3456)AKI (n = 1993)Stages of AKIP valueaComparisons are made between no AKI and AKI using Fisher exact test for categorical variables and or nonparametric Kruskal-Wallis test for continuous variables. (no AKI vs. all AKIP valuebComparisons are made across the stages of AKI using Kruskal-Wallis rank sum test. (trend)1 (n = 927)2 (n = 447)3 (n = 619)Age (yr)61.0 (50.0, 72.0)69.0 (58.0, 78.0)69.0 (58.0, 79.0)71.0 (58.5, 79.0)67.0 (58.0, 76.0)<0.001<0.001Male2047 (59.2)1270 (63.7)556 (60.0)266 (59.5)448 (72.4)0.001<0.001Race0.040.04 Asian304 (8.8)162 (8.1)72 (7.8)35 (7.8)55 (8.9) Black708 (20.5)415 (20.8)190 (20.5)106 (23.7)119 (19.2) White1294 (37.4)818 (41.0)393 (42.4)191 (42.7)234 (37.8) Other/multiracial988 (28.6)506 (25.4)232 (25.0)92 (20.6)182 (29.4) Other/unknown138 (4.0)84 (4.2)38 (4.1)21 (4.7)25 (4.0) Declined24 (0.7)8 (0.4)2 (0.2)2 (0.4)4 (0.6)Ethnicity0.030.03 Hispanic/Latino765 (22.1)380 (19.1)159 (17.2)85 (19.0)136 (22.0) Not Hispanic/Latino2474 (71.6)1479 (74.2)711 (76.7)330 (73.8)438 (70.8) Other/unknown217 (6.3)134 (6.7)57 (6.1)32 (7.2)45 (7.3)Language0.520.12 English2825 (81.7)1608 (80.7)764 (82.4)353 (79.0)491 (79.3) Spanish402 (11.6)238 (11.9)96 (10.4)53 (11.9)89 (14.4) Other229 (6.6)147 (7.4)67 (7.2)41 (9.2)39 (6.3)Insurance status<0.001<0.001 Commercial1329 (38.5)527 (26.4)247 (26.6)98 (21.9)182 (29.4) Medicaid792 (22.9)349 (17.5)159 (17.2)78 (17.4)112 (18.1) Medicare1238 (35.8)1054 (52.9)495 (53.4)260 (58.2)299 (48.3) Self-pay67 (1.9)47 (2.4)19 (2.0)8 (1.8)20 (3.2) Other30 (0.9)16 (0.8)7 (0.8)3 (0.7)6 (1.0)Hospital type0.060.04 Tertiary2420 (70.0)1345 (67.5)635 (68.5)312 (69.8)398 (64.3) Community1036 (30.0)648 (32.5)292 (31.5)135 (30.2)221 (35.7)Comorbid conditionscChronic kidney disease was not included as a comorbid condition because prehospitalization estimated glomerular filtration rate was only available in 15% of patients. HTN1745 (50.5)1292 (64.8)624 (67.3)287 (64.2)381 (61.6)<0.001<0.001 CAD311 (9.0)289 (14.5)136 (14.7)72 (16.1)81 (13.1)<0.001<0.001 HF141 (4.1)208 (10.4)112 (12.1)47 (10.5)49 (7.9)<0.001<0.001 PVD37 (1.1)61 (3.1)22 (2.4)18 (4.0)21 (3.4)<0.001<0.001 Diabetes967 (28.0)830 (41.6)368 (39.7)193 (43.2)269 (43.5)<0.001<0.001 HIV25 (0.7)10 (0.5)5 (0.5)4 (0.9)1 (0.2)0.420.36 Chronic liver disease72 (2.1)42 (2.1)27 (2.9)8 (1.8)7 (1.1)1.000.11 COPD149 (4.3)147 (7.4)74 (8.0)36 (8.1)37 (6.0)<0.001<0.001 Asthma317 (9.2)143 (7.2)74 (8.0)35 (7.8)34 (5.5)0.0120.02 OSA99 (2.9)65 (3.3)27 (2.9)20 (4.5)18 (2.9)0.460.31 Cancer194 (5.6)133 (6.7)65 (7.0)25 (5.6)43 (6.9)0.130.30 Obesity916 (26.5)559 (28.0)244 (26.3)132 (29.5)183 (29.6)0.230.25 Morbid obesity276 (8.0)180 (9.0)81 (8.7)42 (9.4)57 (9.2)0.200.57 BMI (kg/m2)28.4 (25.3, 32.8)29.0 (25.4, 33.5)28.7 (25.5, 33.2)28.7 (24.7, 33.6)29.5 (25.9, 34.0)0.090.04Kidney function Admission SCr (mg/dl)0.95 (0.77, 1.16)1.24 (0.91, 1.82)1.26 (0.91, 1.83)1.30 (0.95, 1.86)1.19 (0.90, 1.79)<0.001<0.001 Discharge SCr (mg/dl)0.80 (0.66, 0.98)1.42 (0.84, 3.16)1.02 (0.72, 1.57)1.38 (0.80, 2.26)4.00 (2.21, 6.12)<0.001<0.001 Peak SCr (mg/dl)0.98 (0.80, 1.20)2.23 (1.40, 4.12)1.50 (1.10, 2.16)2.13 (1.59, 2.91)5.20 (3.40, 7.24)<0.001<0.001 Median SCr (mg/dl)0.86 (0.70, 1.03)1.20 (0.82, 2.00)1.04 (0.75, 1.53)1.10 (0.80, 1.53)2.05 (1.11, 3.55)<0.001<0.001 Admission eGFR (ml/min/1.73 m2)82.5 (62.0, 98.0)56.0 (34.0, 80.0)54.0 (33.0, 81.0)53.0 (32.0, 79.0)62.0 (37.0, 81.0)<0.001<0.001 Discharge eGFR (ml/min/1.73 m2)94.0 (77.0, 107.0)45.0 (17.0, 86.0)69.0 (39.0, 97.0)50.0 (27.0, 89.0)14.0 (8.0, 27.0)<0.001<0.001Medications No. of medications3 (1, 7)6 (2, 10)6 (2, 10)6 (2, 10)5 (1, 9)<0.001<0.001 ACE-I385 (11.9)269 (15.9)119 (14.4)51 (13.4)99 (20.2)<0.001<0.001 ARB516 (16.0)386 (22.8)184 (22.3)84 (22.1)118 (24.0)<0.001<0.001ICU335 (9.7)1060 (53.2)320 (34.5)244 (54.6)496 (80.1)<0.001<0.001Mechanical ventilator122 (3.5)1068 (53.6)288 (31.1)262 (58.6)518 (83.7)<0.001<0.001ECMO0 (0.0)10 (0.5)3 (0.3)5 (1.1)2 (0.3)<0.001<0.001InotropesdInotropes include dobutamine and milrinone.3 (0.1)51 (2.6)10 (1.1)12 (2.7)29 (4.7)<0.001<0.001VasopressoreVasopressors include norepinephrine, epinephrine, vasopressin, dopamine, angiotensin-2 infusion.119 (3.4)1049 (52.6)278 (30.0)252 (56.4)519 (83.8)<0.001<0.001CCI3.0 (1.0, 5.0)5.0 (3.0, 7.0)5.0 (3.0, 7.0)5.0 (3.0, 7.5)4.0 (3.0, 6.0)<0.001<0.001Length of stay (d) Discharged/ expired4.9 (3.0, 7.6)7.8 (5.0, 11.6)7.4 (4.8, 10.9)7.2 (4.2, 12.1)8.6 (5.8, 12.3)<0.001<0.001 Currently hospitalized10.3 (8.5, 13.0)13.2 (10.2, 17.3)12.2 (9.4, 16.2)14.0 (11.0, 18.1)14.0 (11.0, 18.23)<0.001<0.001Disposition<0.001<0.001 Discharged2761 (79.9)519 (26.0)397 (42.8)87 (19.5)35 (5.7) Expired194 (5.6)694 (34.8)208 (22.4)152 (34.0)334 (54.0) Currently hospitalized501 (14.5)780 (39.1)322 (34.7)208 (46.5)250 (40.4)ACE-I, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; BMI, body mass index; CAD, coronary artery disease; CCI, Charleson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; eGFR, estimated glomerular filtration rate; HF, heart failure; HTN, hypertension; ICU, intensive care unit; OSA, obstructive sleep apnea; PVD, peripheral vascular disease, SCr, serum creatinine.Values are median (interquartile range) or n (%).a Comparisons are made between no AKI and AKI using Fisher exact test for categorical variables and or nonparametric Kruskal-Wallis test for continuous variables.b Comparisons are made across the stages of AKI using Kruskal-Wallis rank sum test.c Chronic kidney disease was not included as a comorbid condition because prehospitalization estimated glomerular filtration rate was only available in 15% of patients.d Inotropes include dobutamine and milrinone.e Vasopressors include norepinephrine, epinephrine, vasopressin, dopamine, angiotensin-2 infusion. Open table in a new tab ACE-I, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; BMI, body mass index; CAD, coronary artery disease; CCI, Charleson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ECMO, extracorporeal membrane oxygenation; eGFR, estimated glomerular filtration rate; HF, heart failure; HTN, hypertension; ICU, intensive care unit; OSA, obstructive sleep apnea; PVD, peripheral vascular disease, SCr, serum creatinine. Values are median (interquartile range) or n (%). The relationship between respiratory failure and development of AKI was substantial and is displayed in Table 3. Among patients who required mechanical ventilation, 1068 of 1190 (89.7%) developed AKI compared with 925 of 4259 (21.7%) in nonventilated patients. The majority of severe (stage 3) AKI (518 of 619 [83.6%]) and most patients requiring dialytic support (276 of 285 [96.8%]) occurred in patients on mechanical ventilation. RRT was required in 9 of 4259 nonventilated patients (0.2%) compared with 276 of 1190 patients on ventilators (23.2%).Table 3The proportion of patients with AKI, by requirement for invasive mechanical ventilationNo use of invasive mechanical ventilation (n = 4259)Required invasive mechanical ventilation (n = 1190)P valueaData were compared using the Fisher exact test.No AKI3334 (78.3)122 (10.3)<0.001AKI Any stage925 (21.7)1068 (89.7)<0.001 Stage 1639 (15.0)288 (24.2)<0.001 Stage 2185 (4.3)262 (22.0)<0.001 Stage 3101 (2.4)518 (43.5)<0.001Required renal replacement therapybRenal replacement therapy includes intermittent hemodialysis and continuous renal replacement therapy.9 (0.2)276 (23.2)<0.001AKI, acute kidney injury.Values are n (%).a Data were compared using the Fisher exact test.b Renal replacement therapy includes intermittent hemodialysis and continuous renal replacement therapy. Open table in a new tab AKI, acute kidney injury. Values are n (%). There was a substantial clustering of AKI events at the time of intubation and initiation of mechanical ventilation (Figure 3). Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. The median time from mechanical ventilation to initiation of dialytic therapy was 0.3 (IQR: −41.1, 92.3) hours. Urine studies were available within 24 hours before or 48 hours after the development of AKI in up to 646 of 1993 patients with AKI (Table 4). The median urine-specific gravity was 1.020 (IQR: 1.010, 1.020). By urine dipstick, 36.2% had no heme and 46.1% had 2+ to 3+ positivity. Urine protein was negative in 26.0%, but 2+ to 3+ positive in 42.1%. Automated microscopy detected significant leukocyturia or hematuria in 36.5% and 40.9%, respectively. The urine sodium concentration was <35 mEq/l in 65.6% of patients.Table 4Urine tests results obtained 24 hours before up to 48 hours after the development of acute kidney injuryUrine studiesn (%)Urine sodium (mEq/l) <35aUrine sodium was reported as 5051 (17.9)Specific gravity1.020 (1.010, 1.020)Blood 0, negative or trace196 (36.2) 1+, small96 (17.7) 2+, moderate148 (27.3) 3+, large102 (18.8)Protein 0, negative, trace, or 5221 (36.5) Positive with red blood cells, >5249 (40.9)Values are n (%) or median (interquartile range).a Urine sodium was reported as <20 mEq/l in a few of the enterprise hospitals. Open table in a new tab Values are n (%) or median (interquartile range). We studied various baseline characteristics as potential predictors of AKI in COVID-19 (Table 5). By univariate analysis, increased age, male sex, diabetes mellitus, hypertension, history of cardiovascular disease, increased body mass index (BMI), mechanical ventilation, vasopressor medications, and a history of treatment with renal-angiotensin-aldosterone–inhibiting medications were predictors of AKI. Treatment in a tertiary care hospital was associated with marginally reduced risk. Independent predictors, by multivariate analysis included older age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and use of vasopressor medications. In this analysis, renal-angiotensin-aldosterone–inhibiting drugs were no longer an AKI predictor. As BMI data were missing in 1138 of 4211 patients (27%), we compared 2 multivariate logistic regression models, one including BMI and the other excluding BMI (Supplementary Table S2), with no appreciable change in the risk factors for AKI observed.Table 5Univariate and multivariate logistic regression analyses of risk factors associated with the development of AKIVariableUnadjusted OR95% CIP valueAdjusted ORaVariables were entered into the model when the α level of risk factor was less than 0.15. Age, sex, and race were added into the model regardless of α level.95% CIP valueAge (yr)1.031.02–1.03<0.0011.031.03–1.04<0.001bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.Male1.211.08–1.350.0011.140.97–1.330.10White raceReferenceReferenceReferenceReferenceReferenceReference Asian0.840.68–1.040.110.830.61–1.120.23 Black0.930.80–1.080.321.231.01–1.500.04bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication. Other/mixed0.810.71–0.930.0030.840.69–1.030.09 Unknown0.90.69–1.180.440.740.50–1.110.15Tertiary hospital0.890.79–1.000.050.900.77–1.060.20Diabetes1.841.64–2.06<0.0011.761.49–2.07<0.001bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.Hypertension1.811.61–2.02<0.0011.251.04–1.500.02bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.Cardiovascular diseasecCardiovascular diseases include coronary artery disease, heart failure, and peripheral vascular disease.2.051.77–2.37<0.0011.481.22–1.80<0.001bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.Respiratory diseasedRespiratory diseases include asthma and chronic obstructive pulmonary disease.1.090.93–1.260.29———Obesity, BMI ≥30 kg/m21.121.00–1.260.051.110.94–1.310.22HIV0.690.33–1.440.33———Cancer1.20.96–1.510.111.090.82–1.450.54Chronic liver disease1.010.69–1.490.95———Mechanical ventilation31.6025.80–38.60<0.00110.76.81–16.70<0.001bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.Vasoactive medicationeVasoactive medications include inotropes and vasopressors.31.4025.60–38.40<0.0014.532.88–7.13<0.001bIndependent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.ACE-I or ARB use1.611.42–1.82<0.0010.870.73–1.040.12ACE-I, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; BMI, body mass index; CI, confidence interval; OR, odds ratio.a Variables were entered into the model when the α level of risk factor was less than 0.15. Age, sex, and race were added into the model regardless of α level.b Independent risk factors include increased age, black race, diabetes, hypertension, cardiovascular disease, mechanical ventilation, and vasoactive medication.c Cardiovascular diseases include coronary artery disease, heart failure, and peripheral vascular disease.d Respiratory diseases include asthma and chronic obstructive pulmonary disease.e Vasoactive medications include inotropes and vasopressors. Open table in a new tab ACE-I, angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ARB, angiotensin II receptor blocker; BMI, body mass index; CI, confidence interval; OR, odds ratio. Among 1993 patients who developed AKI during the hospitalization, a total of 780 (39%) were still hospitalized, 519 patients (26%) were discharged and 694 (35%) died. Of those who died, 34% had stage 1, 64% stage 2, and 91% stage 3 (Figure 4). Among the 285 patients who required RRT, 157 died and 9 were discharged from the hospital. Another 119 were still undergoing treatment in the hospital, with 108 still on RRT (90.8%). For patients who developed AKI and survived to hospital discharge, the median peak serum creatinine was 2.34 (IQR: 1.42, 4.25) mg/dl with median at hospital discharge of 1.70 (IQR: 0.96, 3.58). Infection with COVID-19 is primarily a respiratory illness, but other organs including the kidneys are often affected.9Huang C. Wang Y. Li X. et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Abstract Full Text Full Text PDF PubMed Scopus (33292) Google Scholar We found that in a large cohort of hospitalized patients at both tertiary care and community hospitals the rates of AKI were higher than were reported previously in the literature. The important relationship between AKI and respiratory failure is indicated by the following findings. First, severe AKI occurred most commonly in close temporal proximity to the time of intubation and mechanical ventilation. Second, the rate of AKI was 89.7% among patients on ventilators compared with 21.7% among other patients. Third, severe (stages 2 and 3) AKI occurred in 65.5% of patients on ventilators compared with 6.7% of nonventilated patients. Finally, almost all of the patients requiring RRT were on ventilator support (276 of 285 [96.8%]). Taken together, these data strongly suggest that AKI, particularly when severe, is a condition that occurs among patients with COVID-19 who also have respiratory failure. AKI is a common complication among patients hospitalized for a wide range of diagnoses. Among patients hospitalized with COVID-19, we found that 36.6% developed AKI during their hospitalization. This is a higher rate than has been reported previously from China and other areas, from sma