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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 2  |  Page : 377-386
Frequency of deranged renal profile in patients with COVID-19: Tertiary Care Experience from a developing country


1 Department of Internal Medicine, Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan
2 Department of Nephrology, Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan
3 Department of Internal Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan
4 Department of Epidemiology and Biostatistics, Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan

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Date of Web Publication11-Jan-2022
 

   Abstract 


Coronavirus disease-2019 (COVID-19) is a global pandemic, also affecting Pakistan with its first case reported on February 26, 2020. Since then, it has been declared a pandemic by the World Health Organization. Our study aimed to evaluate the renal derangements associated with COVID-19 infection in our population. A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of renal function (n = 362). Out of the 362 patients, 229were admitted in the ward, 133 were in intensive care unit (ICU), 258 of them recovered, while 104 deaths reported. At admission, the renal profile was deranged in almost one-half of ICU admissions and mortalities which increased to two-third during the hospital stay, with around 80% of deaths reported with increased urea and creatinine levels. Among the deceased patients, around one-third of the mortalities developed renal profile derangements during the hospital stay although they were admitted with a normal renal profile. An estimated glomerular filtration rate showed a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 in nonsurviving patients. A hazard ratio of 3.293 (P <0.001) for admitting serum urea and 3.795 (P = 0.009) at discharge and for serum creatinine at 5.392 (P <0.001) on discharge was associated significantly with mortality. Kaplan–Meier plot showed a significant decline in days of survival with deranged urea and creatinine (P <0.001). The deranged renal function in COVID-19 patients is associated with an increased number of ICU admissions as well as mortalities.

How to cite this article:
Asghar MS, Ahsan MN, Akram M, Hassan M, Rasheed U, Adnan SM. Frequency of deranged renal profile in patients with COVID-19: Tertiary Care Experience from a developing country. Saudi J Kidney Dis Transpl 2021;32:377-86

How to cite this URL:
Asghar MS, Ahsan MN, Akram M, Hassan M, Rasheed U, Adnan SM. Frequency of deranged renal profile in patients with COVID-19: Tertiary Care Experience from a developing country. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Jul 6];32:377-86. Available from: https://www.sjkdt.org/text.asp?2021/32/2/377/335450



   Introduction Top


Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome are a group of viruses that belong to the beta coronavirus family.[1] The beta coronaviruses are RNA enveloped and can cause a severe infection of the respiratory system that is accompanied by a high rate of mortality.[1] Among this group, the SARS-CoV-2 is the most infectious and virulent virus that is spreading swiftly across the world.[1] Not only does this virus affect the lungs but also the heart, kidney, and gastrointestinal tract.[1] At the time of writing this article, more than 5.5 million have been affected by the virus with over 350,000 deaths.[2]

One of the more serious and important complications caused by coronavirus disease 2019 (COVID-19) is acute kidney injury (AKI). Multiple studies have reported AKI to occur in their study groups, ranging from 0.5% to 7% among the cases and ranging from 2.9% to 23% in critically ill patients.[3]

A study conducted on 59 COVID-19 patients reported that 32 of them had diminished renal function based on the proteinuria present among the patients.[4] The same study also found increased levels of creatinine and urea (19% and 27%, respectively) among their patients, and abnormalities in the kidneys were visualized on the computed tomography (CT) scans of some of the participants.[4] One study revealed that out of the 52 COVID-19 patients included in their study, 29% of them presented acutely with impairment of their kidney function.[5]

Published studies have placed the approximate occurrence of AKI in COVID-19 patients to be seven days after the virus can be isolated from the patients.[6] The development of AKI in patients usually indicates a more severe prognosis of the disease and multi-organ failure. This risk is increased to 19% in critically ill patients admitted to the intensive care unit (ICU).[7]

Renal derangements occurring in COVID-19 seem to have a multifactorial etiology.[1] Patients can develop sepsis or septic shock resulting in alterations in their hemodynamic status, eventually causing kidney injury.[1] However, it seems that kidney damage also occurs due to factors other than sepsis or its related mechanisms.[1] The development of AKI in COVID-19 patients can be assumed to be caused by the direct effects of the SARS-CoV-2 on the renal parenchyma, as angiotensin-converting enzyme-2 (ACE2) expression in the kidneys was found to be approximately 100 times greater compared to the respiratory system.[8] This assumption is supported by the fact that coronaviruses can be detected in the urine of a subject using PCR, thus indicating the virus has been exposed to or has been in contact with the kidney tubules.[1] The onset of AKI in patients with the SARS-CoV also coincided with the shedding of the virus in the patient’s urine.[1] It is documented in various studies that the SARS-CoV and the SARS-CoV-2 enter target cells using the ACE2 as a receptor.[3] ACE2 is present on the surface of kidney tubular cells, and the infection of the cells leads to a greater inflammatory response, thus resulting in the greater frequency and severity of the renal injury.[3]

Patients infected with SARS-CoV-2 and having pre-existing chronic kidney disease (CKD) are at a higher risk of developing renal derangements.[1] This is due to the abnormal fluid balance that can be caused by low fluid intake and increased fluid loss.[1] Wilson et al found that the patients with ARDS who develop moderate-to-severe AKI were at higher risk of disease severity and mortality.[3] The findings of Wilson et al are supported by a study conducted in New York by the Northwell System which found that among the COVID-19 patients admitted to their hospitals, 36.6% developed AKI, and out of which 87.4% of these patients with AKI required mechanical ventilation.[9] This study showed that severe AKI was more prone to develop around the time the patient would require intubation or assisted ventilation.[9]

The frequency of renal derangements among COVID-19 patients is high. A study conducted in China on critically ill patients infected with the SARS-CoV-2 reported that 29% of their subjects developed renal derangements.[1] The results of one study showed that the mortality rate is significantly higher in COVID-19 patients with AKI as compared to those without it.[1] The mortality rate of critically ill COVID-19 patients with AKI is three times greater than patients without AKI.[1] Wang et al in their meta-analysis showed that the presence of AKI in COVID-19 patients was accompanied by a higher risk of mortality. The severity of AKI corresponds to the levels of creatinine. Results showed that the greater the levels of serum creatinine, the worse the patient’s condition.[10] A meta-analysis reported that patients having levels of creatinine to be 133 μmol/L or higher were associated with a higher risk of a severe course of the disease and mortality.[11]

It is clear that the incidence of renal injury among COVID-19 patients is fairly high, and that its presence is accompanied by a high rate of mortality of patients. It should, therefore, be managed appropriately and treated with caution. This study aims to identify the frequency of renal derangements in intensive care as well as mortalities, to document the renal derangements during the hospital stay, and to identify the factors that might be causing the increased frequency of renal derangements in the intensive care so that clinicians can be aided in making an early diagnosis of the disease and reducing the mortality rate with appropriate medical management.


   Methodology Top


This study was conducted as a single centered, retrospective, observational study, and including all patients who were diagnosed as COVID-19 positive via either nasopharyngeal or oropharyngeal swab for PCR. The diagnostic kit used exploits the principle of realtime fluorescence (RT-PCR), USA-WA1/2020 stock concentration 2.8E+05 TCID 50/mL, with a lower detection limit of 0.003 TCID 50/mL. Nasal swabs were used in 65%, while oral swabs diagnosed 35% of the study population. Once admitted, the patients were monitored for their disease course and baseline laboratory investigations, while the outcome was assessed on follow-up. The data were obtained through the review of medical records, and there was no direct patient interaction. Two-third of the patients were admitted to the ward with mild signs and symptoms, while the rest one-third showed moderate-to-severe disease progress in ICU. Out of the total 362 patients included, 258 were recovered and discharged with a total of 104 deaths reported due to COVID-19, among whom 133 patients were admitted to ICU for critical care management and ventilators. The admitting and discharging renal profiles were documented in all the patients to identify the derangements in severe disease during the hospital stay.

The statistical analysis was conducted by using the IBM SPSS Statistics version 25.0 (IBM Corp., Armonk, NY, USA). All continuous variables were described as mean and standard deviation. The means were then compared using an independent sample t-test. The descriptive statistics for categorical variables were counts and percentages. The comparison of categorical data was done either using the Chi-square test or Fisher’s exact test (if the expected count was less than 5 in more than 20% cells). A P value of <0.05 was considered statistically significant (two tailed). A multinomial regression model was adopted to determine the significant association of renal derangement with mortality. Hazard ratios (HRs) along with the 95% confidence interval were obtained with an appropriate P value to predict the severity of disease and its association with renal derangements. Kaplan–Meier curves were used for survival analysis.


   Results Top


At admission, the renal profile was deranged in almost one-half of ICU admissions and nonsurviving patients. Around one-fifth of the recovered patients also had deranged renal markers, among which 57 out of 258 (22.1%) had elevated creatinine levels [Table 1], while during the hospital course many of them showed improvement in creatinine levels, with only 25 out of 118 (21.2%) left with deranged creatinine at discharge. Among the deceased patients, 54 out of 104 (51.9%) patients had an initial high creatinine, but at discharge, almost 57 out of 73 (78%) of those patients showed deranged creatinine [Table 2]. It implies that around one-third of the mortalities developed deranged creatinine during the hospital stay.
Table 1: Admitting renal profile of COVID-19 patients.

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Table 2: Discharging renal profile of COVID patients.

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Serum urea is also deranged in a similar proportion of the study population, while estimated glomerular filtration rate was also calculated in both surviving and nonsurviving patients showing a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 mL/min/1.73 m2 was documented during the hospital stay of nonsurviving patients [Table 3].
Table 3: Progress of labs from admission to discharge of COVID patients.

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Serum sodium was in the normal range for most of ICU admissions and recoveries, but deceased patients showed an inhospital increase in the levels (P <0.001). Serum potassium has slightly elevated levels at admission as well as at discharge for ICU stay and mortalities. Serum chloride was found not significantly different in severe and nonsevere group of patients. An increased serum bicarbonate levels were noticed in recovering as well as dying patients during hospital stay although the values both at admission and discharge were significantly lower in ICU admission and mortalities.

Most of the deaths have occurred either due to circulatory failure or septic shock, secondary to respiratory or cardiac arrest. In most of these patients, acute renal injury can be postulated due to septic shock, hence contributing to inhospital renal derangements during the hospital stay. Few of the patients also showed secondary bacterial infections, or ventilator-associated pneumonia, which further contributed toward septicemia and further circulatory failure leading to renal hypoperfusion and impending renal injury. [Table 4] lists these contributory factors including the cause of deaths and secondary bacterial infections. A HR of 3.293 (confidence interval of 1.696–6.394, P <0.001) for blood urea at admission and HR of 3.795 (confidence interval of 1.396–10.320, P = 0.009) at discharge was significantly associated with mortalities. Similarly, serum creatinine with an HR of 1.753 (confidence interval of 0.902–3.402, P = 0.097) at admission and 5.392 (confidence interval of 2.114–13.755, P <0.001) at discharge was associated significantly with the death of the patient. A Kaplan–Meier plot showed a significant decline in days of survival among the patients with deranged urea and creatinine at both admission and discharge [Figure 1].
Figure 1: Kaplan–Meier curves of serum urea and creatinine both at admission and discharge.

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Table 4: Demographic data, clinical features, and risk factors of the study population (n=362).

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   Discussion Top


The renal derangements in SARS-CoV-2-infected individuals are vital as the mortality rate is high in these patients. Previously, the SARS-CoV also displayed an association of the infection and AKI, with 6.7% of the patients developing it accompanied with ARDS. The mortality caused by AKI was in 91.7% of the patients; therefore, understanding and pattern of AKI are extremely important.[12]

Our study showed that the renal profile was deranged for half of the patients admitted to the ICU, and this would increase to more than two-third of the nonsurviving patients during hospitalization. This incidence is much lower than the one reported by Pei et al, where the percentage of patients with renal involvement was 75.4% on admission, while AKI on admission was seen in 35 out of 467 patients.[13] Wang et al, found in their study that on admission, the values of creatinine and blood urea were significantly higher in patients who could not survive with the disease as compared to the survivors.[14] Pei et al reported that overall, 4.7% of their patients were observed to have AKI (22 out of 467) according to the KDIGO definition.[13] Compared to our frequency, Yang et al found in their study that 29% of the patients had renal derangement, which was similar to our results.[5] Our results also show that one-third of the patients developed deranged renal functions during hospitalization. This is much lower when compared to the results of Pei et al where they found that 86.4% developed AKI during their hospital stay.[13]

The frequency of deranged renal markers was seen to increase at the time of discharge, with the majority of these subjects being admitted to the ICU. The high frequency of deranged renal profile in the ICU group coincides with what is reported by Yu et al, where they found critical illness was accompanied by a high incidence of AKI in COVID-19 patients.[15] Our frequency of deranged urea and creatinine in ICU patients however is much higher than what was reported by Yu et al, where it was present in 25.2% of the ICU patients.[15] Zhao et al showed in their study that AKI was seen in 5.5% (5/91) of the total subjects, where all 5 patients (16.7%, 5 out of 30 patients) belonged to the critically ill group.[16] The frequency of AKI in nonsurviving patients was 85%, thus showing a high rate of mortality in COVID-19 patients with AKI, similar to our findings. Wang et al showed that AKI occurred in 14 patients (14.1%), but exclusively in non-surviving patients, thus the mortality rate in our study was much higher in comparison.[14] The findings in our study also show a higher rate of mortality associated with deranged renal markers as compared to a study done by Chen et al on deceased patients, where the frequency of deranged renal markers was 25%.[17]

We found that if the serum creatinine was elevated above the baseline, there was a higher chance that the patient was to be admitted to the ICU, as approximately 43.6% of the ICU patients on admission had elevated creatinine levels. This is consistent with the findings of Cheng et al who also reported that patients were more likely to be admitted to the ICU and develop AKI during their hospital stay if their serum creatinine was elevated above the baseline.[18] The high incidence of renal derangements may be due to the effect of the SARS-CoV-2 virus on the kidney, the effect of sepsis and septic shock in the patients (especially those in the ICU), secondary bacterial infections, and the presence of existing CKD (10% patients in our study).

The complications of COVID-19 causing death were assessed by another study which includes acute respiratory distress syndrome (ARDS) (38.3%), cardiac injury (21.7%), liver dysfunction (19.3%), AKI (17.3%), bacteremia/ sepsis (7.7%), and diffuse intravascular coagulation (7.7%),[19] as opposed to our study where ARDS was lower (25.9%), cardiac events (13.4%) shock/hypotension was higher (16.3%) while coagulopathy (12.5%), and multi-organ failure (22.1%) were most frequent causes of death. Hospital-acquired infections were also lower in the same study (9.5%) as compared to our study (14.36%), as well as ventilator-associated pneumonia (10.6%).[19] Another study showed that every three in four patients who were on ventilators had developed AKI during the hospital stay.[20],[21] A systematic review conducted to document renal derangement in the mortalities caused by COVID-19 concluded a high AKI frequency of 94%–96% in non-surviving patients, synchronizing with our study results.

The study had few limitations, including lack of urinary biomarkers for assessing acute renal injury, no urinary output monitoring as there was no patient interaction mentioned in the study design, and relying solely on serum biochemical markers to identify the renal derangements in the study population.


   Conclusions Top


To our knowledge, this is the first study conducted that assesses the frequency of deranged renal profile in the COVID-19 population in the region. Our results were significantly higher as compared to other populations in terms of the high incidence and mortality associated with it. Physicians should be aware of the risk of renal injury developing in most COVID-19 patients during hospitalization and appropriate steps in management should be taken to avoid the factors leading toward it, while further large-scale studies are required to establish an association between those factors and development of renal injury.


   Ethical Approval Top


Ethical approval was obtained in this study from the institutional review board.

Conflict of interest: None declared.



 
   References Top

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Soleimani M. Acute kidney injury in SARS-CoV-2 infection: Direct effect of virus on kidney proximal tubule cells. Int J Mol Sci 2020;21:3275.  Back to cited text no. 1
    
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WHO COVID-19 Dashboard. Covid19.who. int; 2020. Available from: https://covid19.who. int/. [Last accessed on 2020 May 28].  Back to cited text no. 2
    
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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;46:1114-6.  Back to cited text no. 3
    
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Li Z, Wu M, Yao J, et al. Caution on kidney dysfunctions of 2019-nCoV patients. medRxiv 2020.  Back to cited text no. 4
    
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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. 5
    
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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. 6
    
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Ng JJ, Luo Y, Phua K, Choong AM. Acute kidney injury in hospitalized patients with coronavirus disease 2019 (COVID-19): A meta-analysis. J Infect 2020;81:647-79.  Back to cited text no. 7
    
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Fanelli V, Fiorentino M, Cantaluppi V, et al. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care 2020;24:155.  Back to cited text no. 8
    
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Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int 2020;98:209-18.  Back to cited text no. 9
    
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Wang Y, Shi L, Yang H, Duan G, Wang Y. Acute kidney injury is associated with the mortality of coronavirus disease 2019. J Med Virol 2020;92:2335-7.  Back to cited text no. 10
    
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Zheng Z, Peng F, Xu B, et al. Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis. J Infect 2020;81:e16-25.  Back to cited text no. 11
    
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Chu KH, Tsang WK, Tang CS, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int 2005;67:698-705.  Back to cited text no. 12
    
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Pei G, Zhang Z, Peng J, et al. Renal involvement and early prognosis in patients with COVID-19 pneumonia. J Am Soc Nephrol 2020;31:1157-65.  Back to cited text no. 13
    
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Wang D, Yin Y, Hu C, et al. Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. Crit Care 2020;24:188.  Back to cited text no. 14
    
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Yu Y, Xu D, Fu S, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: A cross-sectional study. Crit Care 2020;24:219.  Back to cited text no. 15
    
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Zhao XY, Xu XX, Yin HS, et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: A retrospective study. BMC Infect Dis 2020;20:311.  Back to cited text no. 16
    
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Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ 2020;368:m1091.  Back to cited text no. 17
    
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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. 18
    
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Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020;146:110-8.  Back to cited text no. 19
    
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Fominskiy EV, Scandroglio AM, Monti G, et al. Prevalence, characteristics, risk factors, and outcomes of invasively ventilated COVID-19 patients with acute kidney injury and renal replacement therapy. Blood Purif 2021;50:102-9.  Back to cited text no. 20
    
21.
Bajwa H, Riaz Y, Ammar M, Farooq S, Yousaf A. The dilemma of renal involvement in COVID-19: A systematic review. Cureus 2020;12:e8632.  Back to cited text no. 21
    

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Correspondence Address:
Muhammad Sohaib Asghar
Department of Internal Medicine, Dow University Hospital, Dow University of Health Sciences, Karachi
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.335450

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