Acute Kidney Injury in Coronavirus Disease-19 (COVID-19) Patients Admitted to the Intensive Care Unit (ICU) (COVID-AKI-B)

Acute Kidney Injury in COVID-19 Patients Admitted to the ICU: a Multicenter Cohort Analysis in 9 Large Hospitals in Belgium

The aim of this study is to evaluate the rate and outcomes of COVID-19 associated acute kidney injury (AKI) and use of kidney replacement therapy (KRT) in critically ill COVID-19 patients in ICUs in several large hospitals in Flanders, the northern region of Belgium. We will also explore the associations between several baseline risk factors for AKI, therapeutic strategies and COVID-19 related clinical signs and the occurrence of AKI and use of KRT.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Acute Kidney Injury; COVID-19 Pneumonia
• Intervention / Treatment: Other: Observational study exploring the epidemiology and outcomes of AKI in critical COVID-19 patients admitted to the ICU

Detailed Description

The aim of this study is to evaluate the rate and outcomes of COVID-19 associated acute kidney injury (AKI) and use of kidney replacement therapy (KRT) in critically ill COVID-19 patients in ICUs in several large hospitals in Flanders, the northern region of Belgium. We will also explore the associations between several baseline risk factors for AKI, therapeutic strategies and COVID-19 related clinical signs and the occurrence of AKI and use of KRT.

This will be a cohort analysis of the rate of COVID-19 associated AKI and KRT during the period 1 February 2020 - 31 January 2021 in 6 large hospitals in Flanders Belgium and 3 Flemish University Hospitals. We will collect patients' baseline characteristics, specific treatment for COVID-19, other relevant therapies and severity of illness and ICU and hospital outcome data. AKI will be assessed during ICU stay up to 21 days of ICU stay, and will be defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. In addition, we will assess occurrence of AKI stages, duration of AKI, duration of AKI integrated with severity stage of AKI into the area under the curve of AKI, occurrence of rapid reversal of AKI, occurrence of Acute Kidney Disease (AKD) defined according to KDIGO.

• Study Type: Observational
• Enrollment (Actual): 1286

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2650
    • UZ Antwerp
  • Brugge, Belgium, 8000
    • AZ St-Jan AV
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
  • Ghent, Belgium, 9000
    • Ghent University Hospital
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Turnhout, Belgium, 2300
    • AZ Turnhout

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All consecutive Critical COVID-19 patients admitted to the ICU

Description

Inclusion Criteria:

• Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection confirmed by Polymerase Chain Reaction (PCR) on nasopharyngeal swab or oropharyngeal swab or rectal swab or bronchoalveolar aspirate
• admission to the ICU for monitoring or organ support

Exclusion Criteria:

• asymptomatic COVID-19 patients admitted to the ICU for medical reason not related to COVID-19

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Critical COVID-19; Critical COVID-19 patients admitted to the ICU	Other: Observational study exploring the epidemiology and outcomes of AKI in critical COVID-19 patients admitted to the ICU; Critical COVID-19 patients admitted to the ICU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury (AKI)	AKI occurrence and severity stages defined according to KDIGO	up to day 21 of ICU admission
Kidney outcome	use of KRT and eGFR in patients without AKI (no AKI), AKI, and AKI stages	day 30 after ICU admission
Mortality	Mortality of AKI and no AKI patients will be compared	day 30 after ICU admission
Survival	Survival of no AKI, AKI and AKI stages, AKD, and rapid reversal up to day 30 or hospital discharge whichever comes last	AKI and AKD will be classified up to day 21 of ICU stay, and survival will be assessed up to day 30 or hospital discharge whichever is last

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury (AKI) creatinine criteria	AKI occurrence and severity stages defined according to KDIGO creatinine criteria	up to day 21 of ICU admission
Acute Kidney Injury (AKI) urine output criteria	AKI occurrence and severity stages defined according to KDIGO urine output criteria	up to day 21 of ICU admission
Acute Kidney Injury (AKI), rapid reversal	Occurrence of AKI for 48-h or less	up to day 21 of ICU admission
Acute Kidney Disease (AKD)	Occurrence and severity staging of AKD according to KDIGO criteria	up to day 21 of ICU admission
AKI-Area Under the Curve (AUC)	Assessment of AKI-AUC which is defined as the sum of the daily maximum severity stage of AKI	up to day 21 of ICU admission
Mortality AKD	Mortality of patients with AKD and severity stages of AKD will be compared to no AKI and patients with AKI and different AKI stages	day 30 after ICU admission
Mortality AKI rapid reversal	Mortality of patients with AKI rapid reversal ill be compared to no AKI and patients with AKI and different AKI stages	day 30 after ICU admission
Mortality AKI stage 2-3	Mortality of patients with AKI stage 2 or greater and patients with no AKI or AKI stage 1 will be compared	day 30 after ICU admission
Mortality AKI treated with KRT	Mortality of patients with AKI treated with KRT and patients with no AKI or AKI stage 1, 2 or 3 will be compared	day 30 after ICU admission
Mortality AKI creatinine criteria versus urine output criteria versus full KDIGO	Mortality of patients with AKI and patients with no AKI will be compared	day 30 after ICU admission
Mortality AKI-AUC	Mortality of quartiles of AKI-AUC will be assessed	day 30 after ICU admission
Kidney outcome AKI KDIGO creatinine or urine output	use of KRT and eGFR in no AKI, AKI on creatinine or urine output criteria and AKI stages, Rapid Reversal of AKI, and AKD and stages	day 30 after ICU admission
Duration of AKI and AKD	Duration of AKI, AKI on creatinine or urine output criteria and AKI stages, Rapid Reversal of AKI, and AKD and stages	up to day 21 of ICU admission
Survival AKI-AUC	Survival up to day 30 or hospital discharge (whichever is last) for quartiles of AKI-AUC will be assessed	AKI-AUC will be assessed up to day 21 of ICU stay, and survival will be assessed up to day 30 or hospital discharge whichever is last
Recovery of AKI and AKD	Recovery of AKI, AKI stages, AKD and AKD stages, KRT will be assessed	day 30 after ICU admission
Timing of AKI, AKI severity grades and use of KRT	timing of occurrence of AKI in relation to onset of symptoms, hospital admission, ICU admission	ICU admission up to day 21
KRT modality	initial modality of KRT and anticoagulation used	ICU admission up to day 21
use of KRT	number of KRT treatment days, and KRT free days	ICU admission up to day 21
Subgroup analysis: Mechanical Ventilation	outcomes will be assessed in patients with and without mechanical ventilation at time of start of AKI	ICU admission up to day 21
Subgroup analysis: Chronic Kidney Disease (CKD) (estimated glomerular filtration rate (eGFR)<60 mL/min)	outcomes will be assessed in patients with and without CKD as baseline kidney function	ICU admission up to day 21
Subgroup analysis: elderly (>= 65 y)	outcomes will be assessed in patients older and younger than 65y	ICU admission up to day 21
Subgroup analysis: obese (BMI>30 kg/m2)	outcomes will be assessed in obese patients and non-obese	ICU admission up to day 21
Subgroup analysis: prone ventilation	outcomes will be assessed in patients treated with mechanical ventilation and in prone position	ICU admission up to day 21
Subgroup analysis: extracorporeal membrane oxygenation (ECMO)	outcomes will be assessed in patients treated with ECMO	ICU admission up to day 21

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Jessa Hospital; University Hospital, Antwerp; AZ Sint-Jan AV; AZ Delta; General Hospital Groeninge; AZ Turnhout; Ziekenhuis Oost-Limburg
• Investigators: Study Chair: Eric Hoste, Md, PhD, University Hospital, Ghent; Study Chair: Greet De Vlieger, Md, PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Chawla LS, Bellomo R, Bihorac A, Goldstein SL, Siew ED, Bagshaw SM, Bittleman D, Cruz D, Endre Z, Fitzgerald RL, Forni L, Kane-Gill SL, Hoste E, Koyner J, Liu KD, Macedo E, Mehta R, Murray P, Nadim M, Ostermann M, Palevsky PM, Pannu N, Rosner M, Wald R, Zarbock A, Ronco C, Kellum JA; Acute Disease Quality Initiative Workgroup 16.. Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup. Nat Rev Nephrol. 2017 Apr;13(4):241-257. doi: 10.1038/nrneph.2017.2. Epub 2017 Feb 27.
• Nadim MK, Forni LG, Mehta RL, Connor MJ Jr, Liu KD, Ostermann M, Rimmele 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. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol. 2020 Dec;16(12):747-764. doi: 10.1038/s41581-020-00356-5. Epub 2020 Oct 15. Erratum In: Nat Rev Nephrol. 2020 Nov 2;:
• Ostermann M, Lumlertgul N, Forni LG, Hoste E. What every Intensivist should know about COVID-19 associated acute kidney injury. J Crit Care. 2020 Dec;60:91-95. doi: 10.1016/j.jcrc.2020.07.023. Epub 2020 Jul 28.
• Lameire NH, Levin A, Kellum JA, Cheung M, Jadoul M, Winkelmayer WC, Stevens PE; Conference Participants. Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int. 2021 Sep;100(3):516-526. doi: 10.1016/j.kint.2021.06.028. Epub 2021 Jul 9.
• Ostermann M, Bellomo R, Burdmann EA, Doi K, Endre ZH, Goldstein SL, Kane-Gill SL, Liu KD, Prowle JR, Shaw AD, Srisawat N, Cheung M, Jadoul M, Winkelmayer WC, Kellum JA; Conference Participants. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020 Aug;98(2):294-309. doi: 10.1016/j.kint.2020.04.020. Epub 2020 Apr 26.
• Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10(3):R73. doi: 10.1186/cc4915. Epub 2006 May 12.
• Schaubroeck H, Vandenberghe W, Boer W, Boonen E, Dewulf B, Bourgeois C, Dubois J, Dumoulin A, Fivez T, Gunst J, Hermans G, Lormans P, Meersseman P, Mesotten D, Stessel B, Vanhoof M, De Vlieger G, Hoste E. Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium. Crit Care. 2022 Jul 25;26(1):225. doi: 10.1186/s13054-022-04086-x.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Survival; Recovery; COVID-19; ICU; Epidemiology; Mortality; Acute kidney injury; Acute Kidney Disease; Kidney Replacement Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; COVID-19; Wounds and Injuries; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: BC-08285

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Investigators may propose additional analyses on the dataset. These proposals will be evaluated by the 2 study chairs Eric Hoste and Greet De Vlieger and the study group for eligibility

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No