|Year : 2021 | Volume
| Issue : 4 | Page : 172-178
Acute kidney injury in COVID-19 patients – Dubai Hospital experience: Incidence, risk factors and outcome
Kashif Gulzar, Fakhriya Alalawi, Maseer Ahmed, Hind Alnour, Abdulaziz Saeed, Amna Alhadari
Department of Nephrology, Dubai Health Authority, Dubai Hospital, Dubai, United Arab Emirates
|Date of Submission||26-Apr-2021|
|Date of Decision||04-Jun-2021|
|Date of Acceptance||29-Jun-2021|
|Date of Web Publication||11-Jan-2022|
Department of Nephrology, Dubai Health Authority, Dubai Hospital, Dubai
United Arab Emirates
Source of Support: None, Conflict of Interest: None
Background: The key features of coronavirus disease 2019 (COVID-19) are diffuse alveolar damage and lung failure and also kidney and other organ involvements are reported. However, renal complications are not well explored yet. Aim: In this study, we report distinctive experience with acute kidney injury (AKI) in COVID-19 patients and provide its incidence, risk factors and outcome to improve understanding of this complication. Methods: This retrospective cohort study was conducted in Dubai Hospital from 1 April 2020 to 4 June 2020. We analyse 586 COVID-positive admitted patients' data. Information regarding demographics, comorbidities, medications, clinical and laboratory data and outcomes was collected from patients' electronic medical records. Multivariate analyses were performed to determine the association of AKI with inhospital mortality. Results: The median age was 48.30 (21–92) years; more than 88% of the patients were male. One hundred and thirty-five (23.03%) patients developed AKI during hospitalisation. Male sex, haemodynamic instability, mechanical ventilation, acute respiratory distress syndrome, admission high ferritin, creatinine, D-dimer and low absolute lymphocyte count have identified risk factors for inhospital AKI. The mortality rate in the AKI population was 39.86%, and multivariate analyses reveal that age >75 years, creatinine >1.5 mg/dl at admission, mechanical ventilation and AKI Stage 3 are risk factors associated with high mortality. Conclusion: Incidence of AKI in hospitalised COVID-19 patients is high and associated with high mortality, especially in AKI Stage 3. Planning is needed to handle AKI in COVID patients.
Keywords: Acute kidney injury, acute respiratory distress syndrome, coronavirus disease, inhospital mortality, renal replacement therapy
|How to cite this article:|
Gulzar K, Alalawi F, Ahmed M, Alnour H, Saeed A, Alhadari A. Acute kidney injury in COVID-19 patients – Dubai Hospital experience: Incidence, risk factors and outcome. Hamdan Med J 2021;14:172-8
|How to cite this URL:|
Gulzar K, Alalawi F, Ahmed M, Alnour H, Saeed A, Alhadari A. Acute kidney injury in COVID-19 patients – Dubai Hospital experience: Incidence, risk factors and outcome. Hamdan Med J [serial online] 2021 [cited 2022 Jan 20];14:172-8. Available from: http://www.hamdanjournal.org/text.asp?2021/14/4/172/335375
| Introduction|| |
In late December 2019, multiple case reports of pneumonia of unknown cause were reported in Wuhan city of Hubei Province, China,, and later, this respiratory illness was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after the pathogen was identified with the help of high throughput sequencing. This newly discovered contagious disease was officially called coronavirus disease 2019 (COVID-19) by the World Health Organization and declared a global pandemic on 11 March 2020. In the Middle East, first-ever confirmed case of COVID-19 was reported in the United Arab Emirates (UAE) on 29 January 2020. More than 489,000 cases (0.3% of total cases) of COVID-19 are reported in UAE till date with a mortality of 0.3%, whereas the worldwide mortality rate is 2% so far. The incidence of acute kidney injury (AKI) in COVID-19 patients varies widely (0%–36%), and according to some researchers, this association carries high mortality.,, The reason for kidney involvement is multifactorial, the first virus uses angiotensin-converting enzyme 2 (ACE2) to enter different cells, for example, pulmonary Type 2 alveolar cells, proximal tubular cells and glomerular parietal and visceral epithelial cells,,, and also COVID-19 induces severe inflammation and haemodynamic instability which can cause acute tubular necrosis. Data from the Arab world about renal complication of this disease are scarce. The purpose of our study is to report the incidence of the AKI in COVID-19 patients and to identify the risk factors and associated prognosis to better understand this complication of a newly diagnosed disease.
| Methods|| |
Study design and participants
We conducted a retrospective observational study to identify the incidence, risk factors and prognosis of AKI in COVID-19 patients who were admitted to Dubai Hospital from 1 April 2020 to 4 June 2020. The study was approved by the Scientific Research Committee of the Dubai Health Authority. COVID-19 infection was diagnosed based on clinical presentation, radiographic abnormalities and positive results of polymerase chain reaction on a nasopharyngeal swab. Age <14 years, known dialysis, renal transplant recipient patients and patients with single abnormal creatinine were excluded from this study.
Medical records of the study population were reviewed using electronic medical records (Epic Hyperspace; SALAMA) to retrieve patients' demographic characteristics, laboratory findings and radiological features. Demographic characteristics include age, sex and comorbidities. Laboratory data consisted of full blood count, haemostasis, liver and renal functions, creatinine kinase, lactate dehydrogenase and inflammatory markers including C-reactive protein, procalcitonin, fibrinogen, ferritin and D-dimer. Normal ranges of these parameters were provided by the laboratory. Pulmonary infiltration on chest X-ray was identified as an increased opacity. Pulmonary tuberculosis and oedema were excluded, as identified by the radiologist. The definition of AKI is based on the Kidney Disease Improving Global Outcome (KDIGO) definitions. AKI is defined as an absolute rise in creatinine by ≥0.3 mg/dl within 48 h or an increase in serum creatinine ≥1.5 times the baseline value within 7 days. According to KDIGO, severity stages of AKI are an increase in serum creatinine of 1.5–1.9, 2–2.9 and >3 times the baseline defined as AKI Stages 1, 2 and 3, respectively. Measured serum creatinine on admission day was considered as a baseline, and the highest value was used to categorise the stage of AKI. A decrease in serum creatinine to <1.2 is defined as AKI recovery. Renal replacement therapy (RRT), mechanical ventilation, intensive care admission, duration of hospital stays and inpatient mortality were other outcomes studied.
Continuous variables were described as median and interquartile range values and categorical variables were presented as frequency and percentage. Independent t-test and Mann–Whitney test were used for continuous variables, and categorical data were compared with the help of Pearson's Chi-square test or Fisher's exact test. The association between AKI and inhospital mortality amongst COVID-19 patients was analysed using Cox proportional hazard regression. Kaplan–Meier method and log-rank test were used to assess cumulative survival rates and to calculate statistical significance, respectively. P < 0.05 was considered statistically significant. Statistical Package for Social Sciences (SPSS, Version 26, IBM, U.S.A) was used for statistical analysis.
| Results|| |
Sample size and baseline characteristics
Total 609 patients with COVID infection were admitted in Dubai Hospital in the study period. Twenty-three patients were excluded (single abnormal creatinine reading = 6, dialysis patients [haemodialysis (HD) = 12 and peritoneal dialysis (PD) = 1] = 13 and renal transplant recipient = 4) and 586 patients' data were analysed [Figure 1]. Their mean age was 48.30 (21–92) years and more than 88% of the study populations were male [Table 1]. Patients belonging to different nationalities were present in the study population; 80% of the patients either were from India (190, 32.42%), Pakistan (113, 19.28%), Bangladesh (62, 10.58%), Philippine (50, 8.53%), UAE (27, 4.60%) and Egypt 18 (3.07%). Diabetes mellitus (89, 15.18%) and hypertension (49, 8.36%) were common comorbid, and patients were using medicines such as ACE inhibitors, angiotensin receptor blockers (ARBs), non-steroidal anti-inflammatory drug (NSAID) and aspirin and statins in 5.45%, 5.96%, 7.15% and 10.2%, respectively. Overall, COVID patients were treated with favipiravir and lopinavir/ritonavir in 45.3% and 14.8% of the cases, respectively. 28.15% (n = 165) of all patients require mechanical ventilation. The median value of ferritin, fibrinogen, D-dimer and lactate dehydrogenase was raised. Their median duration of stay was 12.9 (1–85) days. 20.98% (n = 123) were discharged to home, 28.32% (n = 166) were transferred to other hospitals and 18.08% (n = 106) of all patients expired.
|Figure 1: Flow chart of study population of COVID-19 patients admitted in Dubai Hospital|
Click here to view
|Table 1: Baseline characteristics of coronavirus disease 2019 patients admitted in hospital stratified according to kidney injury status|
Click here to view
Acute kidney injury
The incidence of AKI was 23.03% (n = 135) amongst COVID-infected patients during hospitalisation, their median age was 51.85 (22–86) years and the male was 89.62% [Table 1].
According to severity, 79 (58.51%) patients had Stage 3 AKI, and 11.85% (n = 16) and 29.62% (n = 40) suffer from AKI Stages 2 and 1, respectively. Patients who develop AKI during hospitalisation were more likely to have systolic blood pressure < 100 mmHg upon presentation. The baseline laboratory values of patients who did or did not develop AKI are given in [Table 1]. All patients who require dialysis come under the definition of AKI Stage 3. Forty-three (58.22%) out of 79 AKI Stage 3 patients require RRT that is 7.84% of all patients and 34.07% of the AKI population [Table 2]. The modalities of RRT were continuous RRT (CRRT), CRRT + HD and HD only for 40 (93.02%), 2 (4.65%) and 1 (2.32%) patients, respectively. Sixty-five (48.14%) AKI patients require mechanically ventilation, 59.49% (n = 47) had severe AKI and 35.71% (n = 25) of them require RRT. Inhospital recovery of renal functions was complete (CR) for 43.70% (n = 59) and partial (PR) for 56.29% (n = 76) of the patients [Table 1]. Recovery of renal functions was promising in AKI Stage 1 (CR: 85%) and 2 (CR: 43.75%), whereas 75.95% of AKI Stage 3 has partial renal function recovery during the hospital stay [Table 2]. Duration of hospitalisation (days) was significantly higher amongst the AKI population (21 vs. 12 days) [Table 1].
|Table 2: Acute kidney injury patients' characteristics, stratified according to stages of acute kidney injury|
Click here to view
Acute kidney injury and inhospital mortality
Overall, 18.05% (n = 106) of the COVID-19 patients died during hospital admission, which include 59 (39.86%) of AKI-patients [Table 1]. Mortality in patients with AKI Stage 3 was 55.69% (n = 44) and 65.38% (17 out of 26) of the AKI Stage 3 patients who needed RRT and mechanical ventilation [Table 3]. Age more than 75 years, creatinine >1.5 mg/dl at admission, mechanical ventilation and AKI Stage 3 are risk factors associated with high mortality [Table 4]. There is no significant association between inhospital mortality and proteinuria and haematuria.
|Table 3: Acute kidney injury-III patients' characteristics, stratified according to need of renal replacement therapy|
Click here to view
|Table 4: Multivariable Cox proportional hazard ratio for mortality risk factors|
Click here to view
| Discussion|| |
In the present study, we evaluate the incidence and outcome of AKI in COVID-19 patients. We analysed the data of 586 patients, who were admitted with COVID-19 infection between 1 April and 4 June in Dubai Hospital, which provides most of renal-related services in the city. We observed an incidence of AKI in 23.03% of the studied population, where 43.70% had recovered completely. Factors causing AKI in COVID could be COVID specific, i.e. virus-mediated injury, dysregulated inflammatory response, hypercoagulation, microangiopathy and activation of angiotensin II pathway and non-specific factors, i.e. hypoxia, haemodynamic instability and sepsis. AKI in COVID patients is associated with clinical deterioration, less likely to represent the distinctive renal effect of COVID. At the beginning of the COVID pandemic, reports suggest that COVID-19 is not associated with kidney injury,, and soon this association was observed and reported from different parts of the world. Yang X et al. systemically reviewed 24 studies and confirmed a 4.5% incidence of AKI in 4963 COVID patients. We found that our incidence is more than other Asian countries and comparable to Italian and Zahid et al. study (27.29%) from Brookdale University, NY, USA., Hirsch et al. reported 36.6% AKI incidence in 5449 COVID-19 patients in 13 hospitals of New York. In our AKI patients, the rate of intensive care unit admission, administration of mechanical ventilation (48.14% vs. 22.17%), inpatient stay (21 vs. 11 days) and inpatient mortality (43.70% vs. 10.42%) was higher as compared to COVID-19 patients without AKI. These results are commensurate with other studies,, and also we noticed that higher stages of AKI are associated with poor clinical outcomes in COVID-19 patients. In our study population, the incidence of Stage 3 AKI was 13.48%, which is comparable to Zahid et al., but more than other studies mentioned above., We noted that the prevalence of diabetes (19.16%) is twice more common than hypertension (8.34%) in our study population, though the percentage of patients with diabetes and hypertension is less than Chang and Zahid et al. studies., The incidence of severe lung injury requiring mechanical ventilation in our cohort was 18.05% that is more than reported by Chang et al. and Korean study (13.4 and 2.98%, respectively), and the incidence of AKI amongst mechanically ventilated patients was 48.14% that is lower than Zahid et al. study (68%). Many risk factors of AKI were identified. Like previous reports, AKI is also more frequent in male patients and in those who require mechanical ventilation, while in contrast to previous reports, our AKI patients had a more likely history of diabetes while obesity is not a risk factor. ACE inhibitor (ACEi) role in COVID-19 is questionable. ACE2 receptor expression is increased by ACEI that SARS-CoV-2 use to enter cells., Nonetheless, ACE2 degrades pro-inflammatory angiotensin II to angiotensin, so is beneficial in acute respiratory distress syndrome. It is not proved yet if ACEi expedites SARS-CoV-2 virus entry into cells or intracellular viral replication and if ACEi improves acute respiratory distress syndrome outcomes., Neither ACEi nor NSAID use was significantly higher in our COVID patients with AKI. More studies are needed to prove a relationship between ACEi, ARB, NSAID and COVID-19 outcomes. Acute inflammatory markers (ferritin), creatine phosphokinase (CPK) and D-dimer were significantly higher, and absolute lymphocyte count was significantly lower in AKI patients, suggesting a causative relationship between kidney injury and dysregulated immune/inflammatory response, known as a cytokine storm. In our COVID population, mortality was 18.05%. The association between AKI and mortality is significantly strong (AKI 43.70% vs. 10.42% in non-AKI, P = 0.003). There is a higher death rate as AKI stage increases, 22.5%, 37.5% and 55.69% in AKI Stages 1, 2 and 3, respectively. The mortality rate in the American community survey is high,,, and 3–6-fold higher COVID-19-related mortality observed in African American countries than in the white countries, whereas Paek et al. from South Korea reported 3.40% (n = 24) mortality in COVID patients, and out of 28 AKI patients, 13 died (46.40%). Currently, there is no data available from other Arab countries to compare. Out of 135 AKI patients, 43 (31.85%) require RRT and 65 (48.14%) needed mechanical ventilation and also 26 (60.46%) RRT patients required mechanical ventilation. In Stage 3 AKI patients, 54.43% (n = 43) require RRT, and 39.53% (n = 17) of them died. There is no significant improvement in survival with RRT, and mortality remains high in the RRT and non-RRT groups. These findings suggest an early involvement of the palliative care team to define the goals of care in COVID-19 patients with AKI Stage 3. Recovery of renal functions was one of the secondary outcomes. 66.29% (n = 59) of the survivors amongst the AKI group completely recovered renal functions and only two patients remain dialysis dependent. We noted mostly partial recovery of renal functions (87.23%, 41 out of 47 patients) amongst the RRT-AKI group. There are certain limitations in our study. Data were collected retrospectively and many patients' prior renal functions were not available to compare, so patients may have high creatinine on admission secondary to AKI suffered before admission in Dubai Hospital, hence we may underestimate the true overall AKI incidence in COVID-19 patients. There are limitations of our study. there were limited urine studies available to interpret the kidney disease, also number of local patients (from U.A.E) were less than 5%, it limits the general applicability of this data on local population. Since the data was collected retrospectively, investigations like like pre admission creatinine, urine studies & kidney ultrasound that can help in interpretation of renal disease were not available for all patients. Nevertheless, despite the above-mentioned limitations, it is quite clear that the incidence of AKI in COVID-19 patients is high and has a negative impact on patients' morbidity and mortality. In response to the increasing number of AKI patients, we increase our capacity to deliver RRT and also planning to establish a PD programme to strengthen our acute dialysis capacity.
| Conclusion|| |
Our COVID-19 patients experience a high incidence of AKI and mortality, especially in AKI Stage 3, and RRT did not provide much benefit to them. More studies from Arab countries are needed to understand the association between AKI and COVID-19 disease.
This was a retrospective medical study, and informed consent was not required.
This retrospective observational study was conducted at Nephrology Department of Dubai Hospital, Dubai, U.A.E from 1st April to 4th June 2020. Clearance was obtained from Dubai Scientific Research Ethics Committee (DSREC-04/2020_16).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al
. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health-The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis 2020;91:264-6.
Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al
. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020;382:1199-207.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al
. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.
Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al
. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020;97:829-38.
Wang L, Li X, Chen H, Yan S, Li D, Li Y, 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.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al
. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.
Hoffmann M, Kleine-Weber H, Kruger N, Muller M, Drosten C, Pohlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv. 2020.01.31.929042.
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019- nCov. bioRxiv 2020.01.26.919985.
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7.
Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al
. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020;98:219-27.
Batlle D, Soler MJ, Sparks MA, Hiremath S, South AM, Welling PA, et al
. Acute kidney injury in COVID-19: Emerging evidence of a distinct pathophysiology. J Am Soc Nephrol 2020;31:1380-3.
Pei G, Zhang Z, Peng J, Liu L, Zhang C, Yu C, et al
. Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia. J Am Soc Nephrol 2020;31:1157-65.
Yang X, Jin Y, Li R, Zhang Z, Sun R, Chen D. Prevalence and impact of acute renal impairment on COVID-19: A systematic review and meta-analysis. Crit Care 2020;24:356.
Fanelli V, Fiorentino M, Cantaluppi V, Gesualdo L, Stallone G, Ronco C, et al
. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care 2020;24:155.
Zahid U, Ramachandran P, Spitalewitz S, Alasadi L, Chakraborti A, Azhar M, et al
. Acute kidney injury in COVID-19 patients: An inner city hospital experience and policy implications. Am J Nephrol 2020;51:786-96.
Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al
. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int 2020;98:209-18.
Paek JH, Kim Y, Park WY, Jin K, Hyun M, Lee JY, et al
. Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality. PLoS One 2020;15:e0243528.
Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, et al
. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111:2605-10.
Vuille-dit-Bille RN, Camargo SM, Emmenegger L, Sasse T, Kummer E, Jando J, et al
. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids 2015;47:693-705.
Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al
. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005;11:875-9.
Gu H, Xie Z, Li T, Zhang S, Lai C, Zhu P, et al
. Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus. Sci Rep 2016;6:19840.
Wadhera RK, Wadhera P, Gaba P, Figueroa JF, Joynt Maddox KE, Yeh RW, et al
. Variation in COVID-19 hospitalizations and deaths across New York City Boroughs. JAMA 2020;323:2192-5.
[Table 1], [Table 2], [Table 3], [Table 4]