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

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.

• Observational study exploring the epidemiology and outcomes of AKI in critical COVID-19 patients admitted to the ICU (Other): Critical COVID-19 patients admitted to the ICU

Primary outcomes

• Acute Kidney Injury (AKI) [up to day 21 of ICU admission]: AKI occurrence and severity stages defined according to KDIGO
• Kidney outcome [day 30 after ICU admission]: use of KRT and eGFR in patients without AKI (no AKI), AKI, and AKI stages
• Mortality [day 30 after ICU admission]: Mortality of AKI and no AKI patients will be compared
• Survival [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]: Survival of no AKI, AKI and AKI stages, AKD, and rapid reversal up to day 30 or hospital discharge whichever comes last

Secondary outcomes

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

Sex: All, ages: 18 Years to any

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

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• 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. PMID 32777758
• 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. PMID 28239173
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• 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. PMID 32709292
• 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. PMID 16696865
• Results publication: 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. PMID 35879765

• Eric Hoste, Md, PhD, Study chair, University Hospital, Ghent
• Greet De Vlieger, Md, PhD, Study chair, Universitaire Ziekenhuizen KU Leuven