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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM THE ASIA - AFRICA  
Year : 2021  |  Volume : 32  |  Issue : 6  |  Page : 1764-1774
Acute Kidney Injury and Mortality among Patients with Coronavirus Disease-2019 in Pakistan


1 Department of Nephrology and Renal Transplantation, Institute of Kidney Diseases Hayatabad, Peshawar, Pakistan
2 Department of Obstetrics and Gynecology, Hayatabad Medical Complex, Peshawar, Pakistan
3 department of Pharmacy, University of Peshawar, Peshawar, Pakistan
4 Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, Pakistan
5 Department of Pediatrics, Hayatabad Medical Complex, Peshawar, Pakistan
6 Department of Radiology, Institute of Kidney Diseases Hayatabad, Peshawar, Pakistan
7 Institute of Pharmaceutical Sciences, University of Veterinary and Animal Science, Outfall Campus, Civil Lines, Lahore, Pakistan; School of Pharmacy, Monash University, Jalan Lagoon Selatan, Bandar Sunway, Selangor, Malaysia, Pakistan

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Date of Web Publication27-Jul-2022
 

   Abstract 


The kidney is the most vulnerable organ in coronavirus disease-2019 (COVID-19) patients besides the lungs, with evidence of acute kidney injury (AKI). We aimed to find the prevalence of AKI among COVID-19 patients and further evaluate the association of between COVID-19 and AKI along with an understanding of mortality. A prospective observational study was conducted among COVID-19 patients admitted to a tertiary care hospital, Hayatabad Medical Complex, between March 2020 and June 2020. Chi-square test was applied for comparative analysis, whereas for predictors of mortality, odds ratios (OR) were calculated using logistic regression. A total of 606 patients with COVID-19 were admitted to the dedicated ward, of which 250 (41.3%) had AKI and 190 (31.4%) died, whereas, patients having AKI presented 62.1% of mortality. Our study revealed a statistically significant association between AKI and mortality (OR = 3.5; P <0.0001). Moreover, we observed a greater risk of deaths among patients with AKI stage I-III i.e., AKI stage I (OR = 2.4; P <0.0001), stage II (OR = 5.5; P = 0.0001), and stage III (OR = 6.6; P<0.0001). Our study reported AKI and associated mortality in a considerable number of patients with COVID-19. AKI patients have significantly higher chances of death versus non-AKI patients. Further, the risk of mortality increases with further deterioration in kidney function, i.e., patients with AKI stage III showed a higher mortality rate compared with stage II and stage I.

How to cite this article:
Ahmed R, Maula KF, Ali Z, Ismail M, Rehman IU, Maula SF, Ali SM, Khan TM. Acute Kidney Injury and Mortality among Patients with Coronavirus Disease-2019 in Pakistan. Saudi J Kidney Dis Transpl 2021;32:1764-74

How to cite this URL:
Ahmed R, Maula KF, Ali Z, Ismail M, Rehman IU, Maula SF, Ali SM, Khan TM. Acute Kidney Injury and Mortality among Patients with Coronavirus Disease-2019 in Pakistan. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Aug 14];32:1764-74. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1764/352439

   Introduction Top


Since the coronavirus pandemic in December 2019 (in Wuhan, Hubei Province, China), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has propagated swiftly worldwide.[1] Coronavirus disease-2019 (COVID-19) caused by the SARS-CoV-2 has resulted in substantial morbidity and mortality in more than 30 countries across the globe.[2] World Health Organization (WHO) official statistics up to April 14, 2021, have shown that there have been 136,996,364 (~137 million) confirmed cases of COVID-19 including 2,951,832 (~3 million)deaths.[3] The virus after China paved its way to Europe, affecting Spain, Italy, and France, resulting in the confinement of billions of people across the globe.[4],[5] Although the main clinical features of COVID-19 include acute respiratory failure and diffuse alveolar damage,[6] the involvement of other vital organs is also alarming. Besides the lungs, the latest data point toward the fact that the kidneys are the most susceptible organ in patients with COVID-19, with evidence of acute kidney injury (AKI) in up to 37.5% of fatalities.[7] AKI is considered the second most common organ damage inpatients with COVID-19 previously reported in China.[8] Moreover, data have shown the incidence of AKI in the range of 3%−20% in COVID-19 patients.[9],[10],[11] Another study conducted on patients with COVID-19 admitted to intensive care unit has reported AKI in 80% of the patients.[12]

AKI is an independent risk factor for mortality and further deterioration of renal function, so a high frequency of AKI could lead to chronic kidney disease (CKD) and/or end-stage renal disease, decreasing the quality of life of patients.[13],[14] Renal involvement is considered a major and vital complication of COVID-19 leading to an increased risk of death.[15] Hence, an early recognition of AKI and the use of preventive and therapeutic measures can aid in curbing the progression of AKI to more severe stages, and more importantly, decreasing morbidity and mortality.[16] The etiology of AKI in COVID-19 cases has yet to be clarified but is suspected to be multifactorial, with various predisposing factors (e.g., sepsis, hypovolemia, nephrotoxins), acute cardiorenal syndrome, low cardiac output, and cardiovascular comorbidity as key contributors.[16],[17]

Pakistan, being a country in a very susceptible geographical location for this pandemic, is sandwiched between China; the origin and a focal point of spread of COVID-19; and Iran; the epicenter for Islamic countries.[18] Being a neighbor of both epicenters for COVID-19, Pakistan health officials confirmed initial two cases of COVID-19 in Karachi and Islamabad on February 26, 2020.[18] Till date April 15, 2021, the confirmed cases in Pakistan for COVID are 739,818, while in Khyber Pakhtunkhwa, the number of cases are 102,290.[19] Globally, limited data are available on renal disease in patients with COVID-19, whereas, studies are lacking in Pakistan on such data that correlate the COVID-19 and AKI involvement. Thus, an urgent understanding of how the kidneys are affected by COVID-19 is called for. Therefore, we aimed to find the prevalence of AKI among COVID-19 patients and further evaluate the association of COVID- 19 and AKI along with an understanding of mortality.


   Patients and Methods Top


Design

A prospective observational study was conducted between March and June 2020 on patients having COVID-19 admitted to a tertiary care hospital, Hayatabad Medical Complex, Peshawar, which was one of the institutes assigned responsibility for the treatment of patients with COVID-19 by the government.

Participants

All adult patients who were detected positive for COVID-19by the polymerase chain reaction of a nasopharyngeal swab and were hospitalized from March 15, 2020, to June 30, 2020, were included. For patients who needed multiple admissions, we considered only the first hospitalization. Patients were excluded if they were transferred from our hospital to another health-care facility or those who were not willing to participate in this study. Further, patients with known CKD and/or AKI were also excluded from the study.

Ethical approval

Ethical approval was granted by the institutional ethics committee of a tertiary care hospital.

Procedure and data collection

Patients were approached and the objective of the study was explained. Written informed consent was obtained from those who agreed to participate. The demographic characteristics (age and sex), clinical data (symptoms, comorbidities, treatments, complications, and outcomes), and laboratory findings of the patients during hospitalization were collected. AKI was identified according to the Kidney Disease: Improving Global Outcomes definition.[20] The clinical outcomes (i.e., discharges, mortality, and length of stay) were monitored up to June 30, 2020, the final date of follow-up. In this manuscript, mortality refers to “the death of the patient from the date of inclusion in the study till the end of the observation period.”


   Statistical Analysis Top


Data were analyzed using the IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA). Categorical variables were presented as number and frequency. Chi-square test was applied for comparative analysis, whereas for predictors of mortality among COVID-19 patients, odds ratios were calculated using logistic regression. P <0.05 was considered significant.


   Results Top


A total of 682 patients with COVID-19 were admitted to the dedicated ward, of whom 606 were included in the study and 76 patients were excluded. Majority of the patients were above 50 years of age with a mean age of 52.98 years ± 13.3; 74.3% of the patients included in this study were male and the majority of the population were hypertensive and diabetic. The hospital stay of the majority of patients was in the range of 6−10 days, with a mean of 7.82 days ± 5.19. The mean and standard deviation of laboratory parameters as well as medications used are shown in [Table 1].{Table 1}

Of the total of 606 patients, 31.4% of patients died. AKI was significantly higher among patients who expired (P <0.0001). Moreover, we observed a greater risk of mortality among patients with AKI stage I-III (P <0.0001) compared with patients having no AKI [Table 2].
Table 2. Comparative analysis of survivors versus nonsurvivors.
†: Percentage calculated in a total of 416 patients who are alive, ‡: Percentage calculated in a total of 190 patients who were expired, normal oxygen saturation: ≥92%, low oxygen saturation: <92%; intravenous steroids used: Hydrocortisone, dexamethasone, and methylprednisolone.


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Upon performing univariate binary logistic regression analysis, it was revealed that the risk of mortality was 3.5 times significantly higher among patients with AKI (P <0.0001). Further, patients with AKI stage I had 2.4 times higher risk of mortality (P <0.0001) compared with patients having no AKI. Whereas, the risk of mortality among patients with AKI stage II and III was 5.5 (P <0.0001) and 6.6 times (P <0.0001) higher as compared with patients having no AKI [Table 3]. Among the predictors of AKI, the hospital stay of 610 and >10 days was statistically significant, having P <0.043 and 0.005, respectively. Whereas, patients requiring mechanical ventilations were significantly (P = 0.014) at higher risk of AKI, as shown in Supplementary Table 1.
Table 3. Logistic regression analysis of survivors versus non-survivors.
Binary logistic regression used, Reference: Gender: Male; Age: 1�40 years, Acute kidney injury: No, stage of acute kidney injury: No AKI, comorbidities: No, Laboratory parameters: Normal.


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The total number of deaths during the followup period was 190 (31.3%), out of which 118 (62.1%) had AKI, while 72 (37.9%) were non-AKI patients. During the study, a significantly better survival (P = 0.001) was observed among non-AKI patients [22 days (95%CI: 20.2-23.8)] as compared to patients with AKI [13.9 days (95%CI: 12.3-15.5)]. The mean survival time of patients in the group with AKI stage 3 [10.3 days (95%CI: 8.9−11.8)] was lower than the group of patients with AKI stage 1 [16.3 days (95%CI: 13.9−18.7)] and AKI stage 2 [11.3 days (95%CI: 9−13.7)] and was found to be statistically significant (P<0.001). Survival trends of the study population are shown in [Table 4].
Table 4. Survival trends of study participants through Kaplan�Meier survival analysis.

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Cox regression analysis was performed for predictors associated with survival among study population. Group of patients with AKI (Hazard Ratio 0.7) had poor survival and increased chances of death than group of patients without AKI, and the result was statistically significant (P<0.001). Moreover, poor survival was seen among patients with AKI stage 2 and AKI stage 3 and increased serum creatinine levels during survival analysis. However, during multivariate Cox regression analysis, the presence of AKI and of different stages of AKI, only stage 3 of AKI was the only significant factors associated with survival among the study population [Table 5].
Table 5. Univariate and multivariate Cox regression analysis of study participants� predictors for survival.
AKI: Acute kidney injury.


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   Discussion Top


COVID-19 caused by the SARS-CoV-2 is primarily a respiratory illness, but other organs; including the kidneys, are often affected.[8] The exact mechanism of mortality among patients with COVID-19 having AKI is not fully understood. However, it is reported that angiotensin-converting enzyme-2 receptor is found in various organs including kidneys which serves as an entrance door for SARS-CoV-2, thereby leading to cytokine storm and microvascular thrombosis.[21] Analogous to previous literature on a large cohort reporting AKI in hospitalized patients, we have found prevalence of AKI among 41.3% of patients with COVID-19. Similar findings were reported from another study done in China, with 36.9% of hospitalized patients having AKI.[8] This rate of AKI among our study population is much higher than a recent systematic review and meta-analysis conducted, which reported a 28% pooled prevalence of AKI among COVID-19- hospitalized patients.[22] In our study, the prevalence of mortality among patients with COVID-19 having AKI was considerably high as compared to other studies.[23],[24] Moreover, we also observed a higher risk of inhospital deaths for patients with AKI stage I-III which is consistent with another study that reported similar findings.[24] The possible reason for lower AKI and mortality among the stated studies might be due to differences in genetic makeup of patients from different geographic locations and races.

In our study, the severity of respiratory disease seems to be less, as only 7.9% of the patients were in need of invasive ventilation. This is less than another study which reported that 21.8% of the individuals were on ventilators.[8] Analogous to findings reported, individuals who were 70 years or older had a greater risk of mortality;[25],[26] on the contrary, in our study, we did not observe any significant association of mortality with increase in age. Our study revealed that hypertension (36.1%) and diabetes (41.4%) were the most commonly observed comorbidities among patients with COVID-19, on a par with results reported by other studies from New York, one having hypertension (55.7%) and diabetes (33.0%)[8] and the other study having hypertension (56.6%) and diabetes (33.8%), respectively.[27] Another study done on a small sample of patients reported a much higher rate of comorbidities in patients with COVID-19, i.e., hypertension (98.0%) and diabetes (69.0%).[26] Our study found no statistically significant association of comorbidities including hypertension and diabetes with mortality, whereas studies reported a higher risk of mortality in patients with diabetes and hypertension.[28]

Laboratory markers play an important role in better understanding the lethality of a disease. Literature supports the association of many laboratory markers such as elevated lactate dehydrogenase (LDH), elevated serum ferritin, elevated C-reactive protein (CRP), and elevated D-dimer levels with mortality.[29],[30] These findings are not consistent with our study results, where we did not find any significant association of these biomarkers with mortality. The possible reason for this insignificant association in our study may be attributed to the less number of AKI cases among patients with elevated LDH, ferritin, CRP, and D-dimers. Therefore, this study suggests a more careful and thorough evaluation of patients with COVID-19 having AKI. Further, large clinical studies with big data sets are strongly warranted to understand the possible mechanism of COVID-19 association with AKI and associated mortality.

Following are the limitations of the study: first, we could not assess the impact of healthcare infrastructure and different treatment protocols on the mortality rates. Second, the findings of this study cannot be generalized to all population, as the study is conducted only in a single center. Hence, multicenter studies are recommended.


   Conclusion Top


Our study reported AKI and associated mortality in a considerable number of patients with COVID-19. Patients with AKI have significantly higher chances of death versus non-AKI patients. Further, the risk of mortality increases with further deterioration in kidney function, i.e., patients with AKI stage III showed a higher mortality rate compared with stage II and stage I. Therefore, clinicians should increase their awareness of AKI in patients with COVID-19 and devise management plans to prevent mortality associated with AKI. Further, larger studies are strongly warranted in order to better understand the mechanism of death among these patients.

Conflict of interest: None declared.



 
   References Top

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Rubin S, Orieux A, Prevel R, et al. Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019. Clin Kidney J 2020;13:354-61.  Back to cited text no. 12
    
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Rubin S, Orieux A, Clouzeau B, et al. The incidence of chronic kidney disease three years after non-severe acute kidney injury in critically ill patients: A single-center cohort study. J Clin Med 2019;8:E2215.  Back to cited text no. 13
    
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Silver SA, Beaubien-Souligny W, Shah PS, et al. The prevalence of acute kidney injury in patients hospitalized with COVID-19 infection: A systematic review and metaanalysis. Kidney Med 2021;3:83-98.e1.  Back to cited text no. 22
    
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Yan Q, Zuo P, Cheng L, et al. Acute kidney injury is associated with in-hospital mortality in older patients with COVID-19. J Gerontol A Biol Sci Med Sci 2021;76:456-62.  Back to cited text no. 23
    
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Ng JH, Hirsch JS, Hazzan A, et al. Outcomes among patients hospitalized with COVID-19 and acute kidney injury. Am J Kidney Dis 2021;77:204-15.e1.  Back to cited text no. 24
    
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Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020;323:2052-9.  Back to cited text no. 27
    
28.
Acharya D, Lee K, Lee DS, Lee YS, Moon SS, editors. Mortality rate and predictors of mortality in hospitalized COVID-19 patients with diabetes. In: Healthcare. Multidisciplinary Digital Publishing Institute; 2020.  Back to cited text no. 28
    
29.
Sahu BR, Kampa RK, Padhi A, Panda AK. C-reactive protein: A promising biomarker for poor prognosis in COVID-19 infection. Clin Chim Acta 2020;509:91-4.  Back to cited text no. 29
    
30.
Henry BM, Aggarwal G, Wong J, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis. Am J Emerg Med 2020;38:1722-6.  Back to cited text no. 30
    

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Correspondence Address:
Raheel Ahmed
Department of Nephrology and Renal Transplantation, Institute of Kidney Diseases, Hayatabad, Peshawar, Pakistan.
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.352439

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    Tables

  [Table 2], [Table 3], [Table 4], [Table 5]



 

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