Critically ill Covid-19 patients with acute kidney injury: A single-center cohort study

Abstract

Background/Aim: Acute kidney injury (AKI) is a common serious complication associated with morbidity and mortality in critically ill COVID-19 patients. Although there is very limited data on the incidence of AKI in this cohort, conflicting results were recently reported. The incidence of AKI in critically ill COVID-19 patients ranged between 0.5-50% in the early studies. This study aimed to evaluate the incidence and determine the demographic parameters, clinical courses, and outcomes of AKI in critically ill COVID-19 patients admitted to the intensive care unit (ICU). Methods: After ethics committee approval was obtained, critically ill COVID-19 patients admitted to our ICU between June 1- December 30, 2020, were analyzed in this retrospective cohort study. Patients over the age of 18 years who were admitted to the intensive care unit with the diagnosis of COVID-19 or whose real-time polymerase chain reactions (RT-PCR) test were positive were included in the study. Incidence and stages of AKI among the included critically ill COVID-19 patients were evaluated. The patients were divided into two groups according to the presence of AKI to define the risk factors and clinical outcomes. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines based on serum creatinine and urine output. Results: We analyzed seventy-four critically ill confirmed COVID-19 patients. The mean age was 70.7 (14.8) years and 63.5% were male. Thirty-four patients (45.9%) had AKI, 12 patients in stage I (16.2%), 13 patients in stage II (17.6%), and 9 patients in stage III (12.1%). Renal replacement therapy (RRT) was initiated in 28.4% of patients with AKI; 16.2% received intermittent hemodialysis and 12.2%, continuous renal replacement therapy. APACHE II score and GCS at ICU admission were similar in patients with or without AKI (P>0.05), but the SOFA score was significantly higher in patients with AKI (P=0.03). ARDS and shock were significantly higher in patients with AKI than without (P=0.01 and P=0.039, respectively). Compared to the patients without AKI, those with AKI required higher amounts of oxygen therapy (high-flow oxygen therapy, non-invasive mechanical ventilation) and invasive mechanical ventilation (P=0.01 and P<0.001). The ICU mortality was 61.8% for the AKI group compared to 20% among those without (P<0.001). Conclusions: Our study showed that AKI and renal replacement therapy are common in critically ill COVID-19 patients. SOFA score, ARDS, and shock rates were significantly higher among patients who developed AKI. The presence of AKI was associated with higher amounts of oxygen therapy and increased invasive mechanical ventilation. The severity of illness at ICU admission and ICU mortality were higher among those with AKI. Since AKI is seen in almost one in two patients and its development is associated with higher mortality, urine output, and creatinine values should be closely monitored in critically ill COVID-19 patients. It is recommended not to delay RRT therapy as soon as stage 2 AKI develops to preserve kidney function. In addition, optimal hemodynamic monitoring with appropriate fluid management and vasopressor drugs is required to ensure adequate renal perfusion.

Keywords

• COVID-19
• Coronavirus
• Acute kidney injury
• Critically ill
• Intensive care unit

References

1. 1. WHO. Novel coronavirus – China. Jan 12, 2020. http://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/ (accessed Jan 19, 2020).
2. 2. COVID-19 (SARS-CoV-2 INFECTION) guide. Republic of Turkey, Ministry of Health November 7th 2020, Ankara. https://covid19.saglik.gov.tr/TR-66301/covid-19-rehberi.html
3. 3. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-3. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3. PMID: 32015507; PMCID: PMC7095418.
4. 4. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020 Apr;14(2):185-92. doi: 10.1007/s11684-020-0754-0. Epub 2020 Mar 12. PMID: 32170560; PMCID: PMC7088738.
5. 5. Kabbani N, Olds JL. Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk. Mol Pharmacol. 2020 May;97(5):351-3. doi: 10.1124/molpharm.120.000014. Epub 2020 Apr 1. PMID: 32238438; PMCID: PMC7237865.
6. 6. Jiang L, Zhu Y, Luo X, Wen Y, Du B, Wang M, Zhao Z, Yin Y, Zhu B, Xi X. Beijing Acute Kidney Injury Trial (BAKIT) workgroup. Epidemiology of acute kidney injury in intensive care units in Beijing: the multi-center BAKIT study. BMC Nephrol. 2019 Dec 16;20(1):468. doi: 10.1186/s12882-019-1660-z. PMID: 31842787; PMCID: PMC6915890.
7. 7. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11. PMID: 26162677.
8. 8. Gabarre P, Dumas G, Dupont T, Darmon M, Azoulay E, Zafrani L. Acute kidney injury in critically ill patients with COVID-19. Intensive Care Med. 2020 Jul;46(7):1339-48. doi: 10.1007/s00134-020-06153-9. Epub 2020 Jun 12. PMID: 32533197; PMCID: PMC7290076.

9. 9. Zamoner W, Santos CADS, Magalhães LE, de Oliveira PGS, Balbi AL, Ponce D. Acute Kidney Injury in COVID-19: 90 Days of the Pandemic in a Brazilian Public Hospital. Front Med (Lausanne). 2021 Feb 9;8:622577. doi: 10.3389/fmed.2021.622577. PMID: 33634152; PMCID: PMC7900413.
10. 10. Cheng Y, Zhang N, Luo R, Zhang M, Wang Z, Dong L, et al. Risk Factors and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019. Kidney Dis (Basel). 2021 Mar;7(2):111-9. doi: 10.1159/000512270. Epub 2020 Oct 26. PMID: 33821208; PMCID: PMC7649690.
11. 11. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;2:1–138.
12. 12. Republic of Turkey Ministry of Health. General Directorate of Public Health. COVID-19 (SARS-CoV-2) infection guideline,Study of Scientific Board. Ankara, Turkey: Republic of Turkey Ministry of Health; 2020. https://hsgm.saglik.gov.tr/en/covid-19-i-ngilizce-dokumanlar/rehberler.html
13. 13. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019- nCoV) infection is suspected: interim guidance 13 March 2020. Geneva, Switzerland: WHO; 2020.
14. 14. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. doi: 10.1007/s00134-020-06022-5. Epub 2020 Mar 28. PMID: 32222812; PMCID: PMC7101866.
15. 15. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988 Jun;16(3):128-40. doi: 10.1016/0196-6553(88)90053-3. Erratum in: Am J Infect Control 1988 Aug;16(4):177. PMID: 2841893.
16. 16. Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. Restrepo MI, Whitney CG. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019 Oct 1;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST. PMID: 31573350; PMCID: PMC6812437.
17. 17. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019- nCoV) infection is suspected: interim guidance 13 March 2020. Geneva, Switzerland: WHO; 2020.
18. 18. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. PMID: 22797452.
19. 19. McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2020 Jul;2(7):e437-e445. doi: 10.1016/S2665-9913(20)30121-1. Epub 2020 May 7. PMID: 32835247; PMCID: PMC7252093.
20. 20. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001 Nov;86(5):1327-30. PMID: 11816725.
21. 21. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-13. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. PMID: 32007143; PMCID: PMC7135076.
22. 22. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30 PMID: 31986264; PMCID: PMC7159299.
23. 23. Cao M, Zhang D, Wang Y, et al. Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China. Preprint. medRxiv. 2020;2020.03.04.20030395. Published 2020 Mar 6. doi: 10.1101/2020.03.04.20030395
24. 24. Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med. 2020 Jun;46(6):1114-1116. doi: 10.1007/s00134-020-06026-1. Epub 2020 Mar 31. PMID: 32236644; PMCID: PMC7106051.
25. 25. Nisula S, Kaukonen KM, Vaara ST, Korhonen AM, Poukkanen M, Karlsson S, et al. FINNAKI Study Group. Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study. Intensive Care Med. 2013 Mar;39(3):420-8. doi: 10.1007/s00134-012-2796-5. Epub 2013 Jan 5. Erratum in: Intensive Care Med. 2013 Apr;39(4):798. PMID: 23291734.
26. 26. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015 Aug;41(8):1411-23. doi: 10.1007/s00134-015-3934-7. Epub 2015 Jul 11. PMID: 26162677.
27. 27. Jiang L, Zhu Y, Luo X, Wen Y, Du B, Wang M, et al. Acute Kidney Injury Trial (BAKIT) workgroup. Epidemiology of acute kidney injury in intensive care units in Beijing: the multi-center BAKIT study. BMC Nephrol. 2019 Dec 16;20(1):468. doi: 10.1186/s12882-019-1660-z. PMID: 31842787; PMCID: PMC6915890.
28. 28. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 Jun;46(6):1089-98. doi: 10.1007/s00134-020-06062-x. Epub 2020 May 4. PMID: 32367170; PMCID: PMC7197634.
29. 29. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996 Jul;22(7):707-10. doi: 10.1007/BF01709751. PMID: 8844239.
30. 30. Vasilevskis EE, Pandharipande PP, Graves AJ, Shintani A, Tsuruta R, Ely EW, et al. Validity of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-Sedation Scale. Crit Care Med. 2016 Jan;44(1):138-46. doi: 10.1097/CCM.0000000000001375. PMID: 26457749; PMCID: PMC4748963.
31. 31. Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care. 2019 Nov 27;23(1):374. doi: 10.1186/s13054-019-2663-7. PMID: 31775846; PMCID: PMC6880479.
32. 32. Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed ML, et al; STOP-COVID Investigators. Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US. JAMA Intern Med. 2020 Nov 1;180(11):1436-1447. doi: 10.1001/jamainternmed.2020.3596. Erratum in: JAMA Intern Med. 2020 Nov 1;180(11):1555. PMID: 32667668; PMCID: PMC7364338.
33. 33. Raschke RA, Agarwal S, Rangan P, Heise CW, Curry SC. Discriminant Accuracy of the SOFA Score for Determining the Probable Mortality of Patients With COVID-19 Pneumonia Requiring Mechanical Ventilation. JAMA. 2021 Apr 13;325(14):1469-70. doi: 10.1001/jama.2021.1545. PMID: 33595630; PMCID: PMC7890534.
34. 34. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum in: JAMA. 2016 Jul 19;316(3):350. Erratum in: JAMA. 2016 Jul 19;316(3):350. PMID: 26903337.
35. 35. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, 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 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum in: Lancet Respir Med. 2020 Apr;8(4):e26. PMID: 32105632; PMCID: PMC7102538.
36. 36. Xu W, Sun NN, Gao HN, Chen ZY, Yang Y, Ju B, Tang LL. Risk factors analysis of COVID-19 patients with ARDS and prediction based on machine learning. Sci Rep. 2021 Feb 3;11(1):2933. doi: 10.1038/s41598-021-82492-x. PMID: 33536460; PMCID: PMC7858607.
37. 37. Ahmed AR, Ebad CA, Stoneman S, Satti MM, Conlon PJ. Kidney injury in COVID-19. World J Nephrol. 2020 Nov 29;9(2):18-32. doi: 10.5527/wjn.v9.i2.18. PMID: 33312899; PMCID: PMC7701935.
38. 38. Joannidis M, Forni LG, Klein SJ, Honore PM, Kashani K, Ostermann M, et al. Lung-kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Intensive Care Med. 2020 Apr;46(4):654-672. doi: 10.1007/s00134-019-05869-7. Epub 2019 Dec 9. PMID: 31820034; PMCID: PMC7103017.
39. 39. Yap SC, Lee HT. Acute kidney injury and extrarenal organ dysfunction: new concepts and experimental evidence. Anesthesiology. 2012;116:1139-48. [PMID: 22415388 DOI: 10.1097/ALN.0b013e31824f951b]
40. 40. Andres-Hernando A, Dursun B, Altmann C, et al. Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. Nephrol Dial Transplant 2012; 27: 4339-4347 [PMID: 22778179 DOI: 10.1093/ndt/gfs256]
41. 41. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. PMID: 32171076; PMCID: PMC7270627.
42. 42. Peerapornratana S, Manrique-Caballero CL, Gómez H, et al. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. 2019;96:1083-99. [PMID: 31443997 DOI: 10.1016/j.kint.2019.05.026]
43. 43. Chaibi K, Dao M, Pham T, et al. Severe Acute Kidney Injury in Patients with COVID-19 and Acute Respiratory Distress Syndrome [published correction appears in Am J Respir Crit Care Med. 2021 Jan 1;203(1):151.] Am J respir Crit Care Med. 2020;202(9):1299-301. Doi: 10.1164/rccm.202005-1524LE