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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 84-91
Incidence and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019


Al Khezam Dialysis Center, Al Adan Hospital, Hadiya, Kuwait

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Date of Web Publication16-Jun-2021
 

   Abstract 


Patients with more severe cases of coronavirus disease-19 (COVID-19) may be at greater risk for developing acute kidney injury (AKI). The aim of our study was to analyze incidence and outcomes of AKI in critically ill patients with COVID-19. Our study prospectively followed about 198 patients with COVID-19 admitted to intensive care unit (ICU), Al Adan Hospital, Kuwait, for developing AKI and outcomes. Age, gender, nationality, history of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, bronchial asthma, and chronic obstructive pulmonary disease were analyzed. The need for mechanical ventilation (MV), extracorporeal membrane oxygenation, inotropes, and medications was recorded. Causes of AKI, indication of dialysis, dialysis modality, dialysis outcomes, and mortality were analyzed. Our study reported that61 out of 198 (30.8%) ICU patients positive for COVID-19, developed AKI according to the Kidney Disease Improving Global Outcomes definition of AKI. Forty-eight out of 61 (79%) patients need continuous renal replacement therapy using continuous venovenous hemodiafiltration. Thirty-seven (61%) out of 61 patients were with severe sepsis syndrome. The most common cause of AKI was sepsis, cytokine storm, hypovolemia, heart failure, MV, and nephrotoxic drugs. Twenty-four patients (39%) out of 61 patients died, and the most common cause of death was sepsis, cytokine storm with respiratory failure, heart failure, and AKI. The outcome of AKI was as follows: six patients (10%) had complete recovery, five patients had partial recovery (8%), and 26 (43%) patients became dialysis dependent. Incidence of AKI is high in ICU COVID-19 patients and is associated with poor outcomes and high mortality. Early detection and specific therapy of kidney changes, including adequate hemodynamic support and avoidance of nephrotoxic drugs, may help to improve critically ill patients with COVID-19.

How to cite this article:
Abdallah E, Al Helal B, Asad R, Hemida M, Nawar E, Kamal M, Reda M, Baharia A, Galal A, Hassan A, Awaga A, Salam M, Shama A. Incidence and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019. Saudi J Kidney Dis Transpl 2021;32:84-91

How to cite this URL:
Abdallah E, Al Helal B, Asad R, Hemida M, Nawar E, Kamal M, Reda M, Baharia A, Galal A, Hassan A, Awaga A, Salam M, Shama A. Incidence and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2021 Sep 22];32:84-91. Available from: https://www.sjkdt.org/text.asp?2021/32/1/84/318551



   Introduction Top


Coronavirus disease-2019 (COVID-19) is the official name given by the World Health Organization to the disease caused by the novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease has rapidly spread around the world after its initial recognition in Wuhan, Hubei Province, China.[1] Pulmonary involvement with diffuse alveolar damage and respiratory failure has been the major disease focus in patients with COVID-19; however, recent reports have highlighted the fact that acute kidney injury (AKI) is also relatively common in this infection and is associated with increased morbidity and mortality.[2] The aim of our study was to analyze incidence and outcomes of AKI in critically ill patients with COVID-19.


   Methods Top


Our study prospectively followed up about 198 patients with COVID-19 admitted to intensive care unit (ICU), during the period from April 23, 2020 to July 6, 2020, Al Adan Hospital, Kuwait, for developing AKI and outcomes. Age, gender, nationality, history of hypertension (HTN), diabetes mellitus (DM), ischemic heart disease (IHD), congestive heart failure (CHF), bronchial asthma (BA), and chronic obstructive pulmonary disease (COPD) were analyzed. The need for mechanical ventilation (MV), extra-corporeal membrane oxygenation (ECMO), inotropes, hydroxychloroquine, remdesivir, lopinavir, tocilizumab, steriods, kelatra, plasma transfusion, and antibiotics were recorded. Complications such as myocardial infarction (MI), cerebrovascular accident (CVA), gastrointestinal tract hemorrhage, pancreatitis, CHF, arrhythmias, and pulmonary embolism (PE) were recorded. Renal function test, liver function tests, cardiac enzymes, blood sugar, CBC, C-reactive protein (C-RP), lactic dehydrogenase, and ferritin were done regularly. Causes of AKI, use of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBS) before AKI, and indication of dialysis, dialysis modality, dialysis outcomes, and mortality were analyzed.


   Statistical Analysis Top


The mean and standard deviation and percentage of the results and paired t-tests to compare AKI and mortality in nondiabetic and nonhypertensive patients and non-IHD and non-CHF patients with AKI and mortality in patients with DM, HTN, IHD, and CHF were done. All statistical analyses were performed using MedCal software (Version 5, 2019 MedCalc Software bv, San Diego, CA, USA). P = 0.05 was used as a significance level.


   Results Top


Sixty-one out of 198 (30.8%) ICU patients positive for COVID-19 at Al Adan Hospital, Kuwait, developed AKI according to the Kidney Disease Improving Global Outcomes definition of AKI,[3] with a mean value of age as 52.97 ± 8.4 years and mean value of serum creatinine as 308.23 ± 141.3 umol/L [Table 1]. Fifty-seven (93%) patients were anuric and four (7%) patients were oliguric. Twenty-two of 61 (36%) patients had DM, 21 patients (34%) had HTN, seven patients (11%) had IHD, two patients (3%) had CHF, four patients (6.5%) had BA, and one patient (1.6%) had COPD. The nationality of 61 patients was 24 (39%) Indian, seven (11%) Kuwaiti, four (6.5%) Pakistani, one (1.6%) Afghan, three (5%) Egyptian, one (1.6%) Syrian, one (1.6%) Nepali, three (5%) Jordanian, nine (15%) Bangladeshi, five (8%) Filipino, one (1.6%) Iraqi, one (1.6%) Yemeni, and one (1.6%) American. Fifty-three (87%) patients were on MV, seven (11%) patients need ECMO, and one (1.6%) patient needed high flow O2 with face mask. Thirty-five (57%) patients were on inotropic support and other medications are shown in [Table 1]. Forty-eight out of 61 (79%) patients need continuous renal replacement therapy (CRRT) using continuous venovenous hemodiafiltration (CVVHDF) and 13 (21%) patients need conservative treatment. Thirty-seven (61%) out of 61 patients were with severe sepsis syndrome and mean value of C-RP was 340.52 ± 236.7. Mean value of lactic dehydrogenase and ferritin was 435.8 ± 124.6 and 1524.57 ± 513.72, respectively. The most common cause of AKI was sepsis, cytokine storm, hypovolemia, heart failure, MV with high positive end-expiratory pressure (PEEP) and nephrotoxic drugs. The most common complications were MI CVA, gastro-intestinal bleeding, pancreatitis, CHF, arrhythmias, and PE shown in [Figure 1]. Twenty-four patients (39%) out of 61 patients died [Figure 2], mortality with DM alone was 2% and HTN alone was 5%, and both DM and HTN was 7% [Table 1] and the most common cause of death was sepsis, cytokine storm with respiratory failure, heart failure, and AKI. The outcome of AKI was six patients (10%) with complete recovery, five patients with partial recovery (8%), and 26 (43%) patients dialysis dependent [Table 1] and [Figure 2].
Figure 1: Complications among coronavirus disease-19 patients with acute kidney injury.
PE: Pulmonary embolism, CHF: Congestive heart failure, GIT: Gastrointestinal tract hemorrhage, MI: Myocardial infarction.


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Figure 2: Outcomes of the 61 coronavirus disease-19 patients with acute kidney injury.

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Table 1: Clinical and laboratory characteristics of 54 acute kidney injury-coronavirus disease-19 patients.

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AKI in nondiabetic and nonhypertensive patients was high compared with diabetic and hypertensive patients [95% confidence interval (CI): 3.4486% to 25.6267%; P <0.0143] [Figure 3]. Mortality in nondiabetic and nonhypertensive patients was high compared with mortality in diabetic and hypertensive patients (95% CI: 17.4384% to 45.2149%; P<0.0001) [Figure 4] and IHD and CHF (95% CI: 23.6089% to 49.6424%; P<0.0001). The presence of DM, HTN, IHD, CHF, BA, and COPD and holding of ACEI/ARBS did not increased incidence of AKI or mortality.
Figure 3: AKI in patients with diabetes mellitus, hypertension, and both DM and HTN in coronavirus disease-19 patients.
AKI: Acute kidney injury, DM: Diabetes mellitus, HTN: Hypertension.


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Figure 4: Mortality in acute kidney injury coronavirus disease-19 patients with diabetes mellitus and hypertension) and total mortality.
DM: Diabetes mellitus, HTN: Hypertension.


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   Discussion Top


Our study reported that 61 out of 198 (30.8%) ICU patients positive for COVID-19, developed AKI according to KDIGO definition of AKI. Forty-eight out of 61 (79%) patients need CRRT using CVVHDF. Thirty-seven (61%) out of 61 patients were with severe sepsis syndrome. The most common cause of AKI was sepsis, cytokine storm, hypovolemia, heart failure, MV, and nephrotoxic drugs. Mortality was 24 patients (39%) out of 61 patients, and the most common cause of death was sepsis, cytokine storm with respiratory failure, heart failure, and AKI. The outcome of AKI was six patients (10%) with complete recovery, five patients with partial recovery (8%), and 26 (43%) patients dialysis dependent.

The mainstays of kidney management for inpatients with AKI, regardless of COVID-19 status are volume management, blood pressure stability, and medications adjustment if indicated. When kidney function deteriorates to the point that the kidneys are unable to filter toxins or regulate volume status, dialysis becomes the next step. The overall approach was by supportive measures including dialysis.

Patients with more severe cases of COVID-19 may be hemodynamically unstable and may not be able to follow the usual form of intermittent hemodialysis. In patients who are critically ill, CRRT, the prolonged gentle form of dialysis was used which is usually better tolerated.

Studies have shown that many COVID-19 patients tend to have comorbidities associated with kidney function including high blood pressure, diabetes, and obesity. Not all of these patients will develop AKI, but if these chronic conditions are not appropriately managed, they can compromise kidney health.[4] Our study revealed that DM and HTN and IHD and CHF did not associated with increased incidence of AKI and mortality compared with COVID-19 patients without DM, HTN, IHD, and CHF.

Many studies reported the incidence of AKI in an overall hospital setting, varying from 0% to 14.7%.[5],[6],[7],[8],[9],[10],[11] AKI occurred in 86 out of 2702 hospitalized patients. Meta-analysis of proportions demonstrated a pooled incidence rate of AKI of 3% (95% CI 1%–7%, I2 = 93.8%) in all hospitalized patients. In our study, the incidence of AKI in ICU patients with COVID-19 was 30.8%, which is comparable with four studies that reported the incidence of AKI in an ICU setting, varying from 8.3% to 28.8%.[7],[10],[12],[13] AKI occurred in 25 out of 122 ICU patients. Meta-analysis of proportions demonstrated a pooled incidence of AKI of 19% (95% C.I. 9%–31%, I2 = 49.6%) in ICU patients. Six studies reported the incidence of RRT use in an overall hospital setting, varying from 0.5% to 7.3%.[6],[7],[8],[9],[10],[11] RRT was used in 31 out of 2001 hospitalized patients. Meta-analysis of proportions revealed a pooled incidence of RRT use of 2% (95% CI: 1%–4%, I2 = 80.8%) in hospitalized patients. Only three studies reported the incidence of RRT use in an ICU setting, varying from 5.6% to 23.1%.[7],[10],[13] RRT was used in 14 out of 101 ICU patients. Meta-analysis of proportions revealed a pooled incidence of RRT use of 13% (95% CI: 4%–25%, I2 = 47.5%). In our study, 48 out of 61 (79%) patients need CRRT using CVVHDF in ICU COVID-19 patients with AKI.

The cause of AKI in COVID-19 is likely to be multifactorial (e.g., sepsis, hypovolemia, and nephrotoxins) as important contributors.[14] Heart failure, particularly right ventricular failure secondary to COVID-19 pneumonia, might lead to kidney congestion and subsequent AKI. Similarly, left ventricular failure might lead to low cardiac output, arterial underfilling, and kidney hypoperfusion (cardiorenal syndrome).

Virus particles were reported to be present in renal endothelial cells in autopsy data, indicating viremia as a possible cause of endothelial damage in the kidney and a probable contributor to AKI.[15]

In addition, SARS-CoV-2 can directly infect the renal tubular epithelium and podocytes through an angiotensin-converting enzyme 2 (ACE2)-dependent pathway and cause mito-chondrial dysfunction, acute tubular necrosis, the formation of protein reabsorption vacuoles, collapsing glomerulopathy, and protein leakage in Bowman’s capsule.[16],[17]

SARS-CoV-2-related immune response dysregulation, as indicated by observed lymphopenia and cytokine release syndrome (cytokine storm) might be another potential mechanism of AKI.[18],[19]

Rhabdomyolysis, macrophage activation syndrome, and the development of microemboli and microthrombi in the context of hypercoagulability and endotheliitis might be other contributors to AKI.[15],[20]

AKI is a well-recognized factor of poor prognosis.[21] In SARS-CoV-2 infection, five studies have found a significant association between kidney failure and death.[5],[22],[23],[24],[25] Interestingly, Cheng et al[5] have found that only AKI stage 2 or higher was associated with a greater risk of mortality [hazard ratio: 3.53 (1.5–8.27)]. Furthermore, in our study, AKI is associated with poor outcomes and high mortality in ICU patients with COVID-19.


   Conclusions Top


Incidence of AKI is high among COVID-19 patients admitted to ICU and is associated with poor outcomes and high mortality. Several mechanisms are possibly involved in AKI during COVID-19 including sepsis, hypovolemia, nephrotoxic drugs, high PEEP, heart failure, a direct viral injury, an imbalanced RAAS activation, inflammatory cytokines, and a procoagulant state. Early detection and specific therapy of kidney changes, including adequate hemodynamic support and avoidance of nephrotoxic drugs, may help to improve critically ill patients with COVID-19.


   Acknowledgment Top


Many thanks to all my colleagues in Al Khezam dialysis center for following, caring, and management and helping in collecting data of COVID-19 patients with AKI in ICU.

Conflict of interest: None declared.



 
   References Top

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Zhu N, Zhang D, Wang W. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.  Back to cited text no. 1
    
2.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 2
    
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Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020;97:829-38.  Back to cited text no. 5
    
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Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 6
    
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Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 7
    
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Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802-10.  Back to cited text no. 8
    
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Wang L, Li X, Chen H, et al. Coronavirus disease 19 infection does not result in acute kidney injury: An analysis of 116 hospitalized patients from Wuhan, China. Am J Nephrol 2020;51:343-8.  Back to cited text no. 9
    
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Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 10
    
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Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 11
    
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Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA 2020; 323:1612-4.  Back to cited text no. 12
    
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Yang 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;8:475-81.  Back to cited text no. 13
    
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Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019;394:1949-64.  Back to cited text no. 14
    
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Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395:1417-8.  Back to cited text no. 15
    
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Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020;98:219-27.  Back to cited text no. 16
    
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Larsen CP, Bourne TD, Wilson JD, Saqqa O, Sharshir MA. Collapsing glomerulopathy in a patient with coronavirus disease 2019 (COVID-19). Kidney Int Rep 2020;5:935-39.  Back to cited text no. 17
    
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Zhou 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;395:1054-62.  Back to cited text no. 18
    
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Ronco C, Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol 2020;16:308-10.  Back to cited text no. 19
    
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Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020;382:e38.  Back to cited text no. 20
    
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Murugan R, Kellum JA. Acute kidney injury: What’s the prognosis? Nat Rev Nephrol 2011;7:209-17.  Back to cited text no. 21
    
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Wen C, Yali Q, Zirui G, et al. Prevalence of Acute Kidney Injury in Severe and Critical COVID-19 Patients in Wuhan, China. Rochester, NY: Social Science Research Network; 2020.  Back to cited text no. 22
    
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Li Z, Wu M, Yao J, et al. Kidney Dysfunctions of COVID-19 Patients: A Multi-Centered, Retrospective, Observational Study. Rochester, NY: Social Science Research Network; 2020.  Back to cited text no. 23
    
24.
Xu S, Fu L, Fei J, et al. Acute kidney injury at early stage as a negative prognostic indicator of patients with COVID-19: A hospital-based retrospective analysis. medRxiv 2020. 25. Chen R, Liang W, Jiang M, et al. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest 2020;158:97-105.  Back to cited text no. 24
    

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Correspondence Address:
Emad Abdallah
Al Khezam Dialysis Center, Al Adan Hospital, Hadiya
Kuwait
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DOI: 10.4103/1319-2442.318551

PMID: 34145117

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