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 Table of Contents  
Year : 2022  |  Volume : 10  |  Issue : 3  |  Page : 47-51

Acute kidney injury: A potential mortality indicator in the second wave of COVID-19 pandemic in India

1 Department of Physiology, Defense Institute of Physiology and Allied Sciences, Delhi, India
2 Department of Community Medicine, AFMC, Pune, India
3 Department of Medicine, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
4 Department of Radiology, IDS, Delhi, India

Date of Submission21-Apr-2022
Date of Decision23-Jun-2022
Date of Acceptance25-Jun-2022
Date of Web Publication28-Jul-2022

Correspondence Address:
Arun Kumar Yadav
Department of Community Medicine, AFMC, Pune, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjhs.mjhs_6_22

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Background: Coronavirus disease-2019 (COVID-19) has protean clinical presentation, influencing almost every organ. The number of COVID-19 patients with acute kidney injury (AKI) is expanding, and the incidence of kidney injury in COVID-19 patients with severe disease is higher than in patients with mild disease.
Objectives: The objective of the study is to find out the association of AKI with COVID-19 deaths.
Methods: A case–control study was designed with a total of 172 patients. This included 92 death cases and 80 discharged cases in a dedicated COVID-19 hospital, critical care and fully intensive care unit equipped, in the peak of the second wave of COVID pandemic. Various biochemical parameters and inflammatory markers were studied to find out the mortality indicators in these severe COVID-19 cases.
Results: Significantly elevated AKI markers such as urea (mean 58.5 vs. 37.1, P < 0.05), uric acid (mean 5.67 vs. 4.18, P < 0.05), and blood urea nitrogen (mean 26.9 vs. 17.3, P < 0.05) were detected in the death group compared to discharge group. This was accompanied by significantly elevated markers of inflammation such as total leukocyte count (TLC) (mean 16082 vs. 12100, P < 0.05), interleukin (IL-6) (mean 194.9 vs. 58.7, P < 0.05), C-reactive protein (mean 28.45 vs. 9.73, P < 0.05), and ferritin (mean 761.4 vs. 608.2, P < 0.05) in the death group.
Conclusion: Significant AKI was noticed in the death group and AKI was further positively correlated with inflammatory markers C-reactive protein, ferritin, IL-6, d-dimer, and TLC levels.

Keywords: Acute kidney injury, coronavirus disease-2019, C-reactive protein, liver function tests, second wave

How to cite this article:
Singh K, Yadav AK, Aggarwal R, Alam A. Acute kidney injury: A potential mortality indicator in the second wave of COVID-19 pandemic in India. MRIMS J Health Sci 2022;10:47-51

How to cite this URL:
Singh K, Yadav AK, Aggarwal R, Alam A. Acute kidney injury: A potential mortality indicator in the second wave of COVID-19 pandemic in India. MRIMS J Health Sci [serial online] 2022 [cited 2023 Feb 3];10:47-51. Available from: http://www.mrimsjournal.com/text.asp?2022/10/3/47/352630

  Introduction Top

Severe acute respiratory syndrome coronavirus 2 is highly infectious and has a protean clinical presentation. Coronavirus disease-2019 (COVID-19) results in lung involvement in the form of viral pneumonia, inflammatory infiltrates, and endothelial damage, resulting in microvascular coagulopathies and acute respiratory distress syndrome, leading to respiratory failure, which are well documented.[1],[2] The expanding information suggests that COVID-19 is a systemic disease affecting also other organs/systems including liver, heart, kidney, and coagulation.[1],[3] Liver injury may predispose for early progression and rapid worsening in patients with COVID-19, hence should be monitored closely for liver dysfunctions.[4]

Acute kidney injury (AKI) is frequently found in critically ill patients and substantial morbidity and mortality is associated with it.[5] Renal involvement was considered negligible initially and AKI used to be ignored.[6] Recently, evidence shows that AKI is prevalent in COVID-19 patients and kidney is invaded.

Although there is a wide variation in the reported incidence of AKI among hospitalized patients with COVID-19, recent studies from the United States have suggested an incidence as high as 37%–40%.[7],[8],[9] Poor prognosis has been observed in the AKI among hospitalized patients,[10] and on the other hand, patients who survive AKI appear to be at increased risk for death and incident chronic kidney disease (CKD).[11]

The etiology of the diseases condition COV-AKI is likely to be variable. First, remote organ injury, including AKI, can simply be a consequence of critical hypoxia. It can also be due to significant systemic hyperinflammation in critically ill patients with COVID-19 exhibit, and a small number may even develop a macrophage-activation syndrome-like phenotype with cytokine storm and high plasma ferritin. The other evidence is direct infection of renal tubule epithelial cells (RTECs). A variety of epithelial cells express the angiotensin-converting enzyme 2 receptor and this receptor is used by β-coronaviruses to enter the cells.[12],[13] There is also evidence of direct infection of RTEC recently.[14]

Hence, the rationale for targeting AKI is that it may contributes to short-term morbidity and mortality and long-term complications including CKD. However, there are few studies on mortality and in Indian settings. Hence, the present study was conducted to find out the association among COVID-19 mortality and AKI.

  Methods Top

This was a case–control study conducted in a dedicated COVID-19 hospital, critical care and fully intensive care unit (ICU) equipped, in northern part of India between May 2, 2021, and June 6, 2021, peak of the second wave of COVID-19 pandemic. The hospital was a makeshift hospital with 500 beds. Only severe cases of COVID-19 as per the ICMR guidelines were admitted to the hospital. The study was approved by the institutional ethical committee. A total of 1684 patients were admitted during the second wave. The clinical information, such as symptoms, age, gender, and history were recorded upon admission to the hospital. Laboratory data were directly retrieved from the central lab system for all the patients admitted to the hospital. These data included routine blood test, blood chemistry, coagulation test, and inflammatory markers. All patients were treated as per the directions of the guidelines. Cases (mortality cases) were randomly chosen from all the death cases. There were total of 802 (47.6%) deaths out of 1684 admitted during the period. Similarly, controls who have recovered were randomly chosen from those who recovered. The data about the laboratory records and other parameters at the time of admission were collected from the laboratory records and case sheets. The data were anonymized before analysis and confidentiality was assured. Since it was a data-based study, no consent was taken. Looking at the serious condition of the patients involved in the study informed consent was not taken; however, the data confidentiality was maintained.

The sample size was calculated for hypothesis testing for two means for effect size of 0.45 assuming 80% power, 5% alpha error, and two-tailed tests. The calculated sample size was 78 in each group. However, we studied 92 death cases and 80 recovered cases, a total of 172 patients, to cater for the incomplete data if any during our analysis. The inclusion criteria were severe COVID-19 cases according to ICMR guidelines such as breathlessness, respiratory rate >30/min, and SpO2 <90% on room air. The exclusion criteria were chronic dialysis treatment, kidney transplant, or CKD Kidney Disease: Improving Global Outcomes (KDIGO) Stage 4 (estimated glomerular filtrate rate >30 ml/min) at the time of admission.

Liver injury pattern was classified as hepatocellular, cholestatic, or mixed. Patients who had raised alanine transaminase (ALT) and/or aspartate transaminase (AST) more than 3 × the upper limit unit of normal (ULN) were classified as hepatocyte type; patients who had raised ALP or GGT twice the ULN were classified as cholangiocyte type; and patients who had a combination of both ALT/AST elevated more than 3 × the ULN and ALP/GGT twice the ULN were classified as mixed type.[15] AKI was defined according to KDIGO criteria as follows: stage 1 as an increase in serum creatinine (Scr) level by 0.3 mg/dL within 48 h or 1.5–1.9 times increase in Scr level from baseline within 7 days; stage 2, as 2–2.9 times increase in Scr level within 7 days; and Stage 3, as 3 or more times increase in Scr level within 7 days or initiation of dialysis.[16]

The data were collated in MS Excel. The continuous variables were described as mean and standard deviation if they follow normal distribution or median and interquartile range otherwise. The Shapiro–Wilk test was used for normality. The categorical variables were described as number and percentages. The unpaired “t”-test were used for finding the difference between means in two groups. Chi-square test was used for categorical variables. The data were analyzed using StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX, USA: StataCorp LLC. P < 0.05 was taken as statistically significant.

  Results Top

A total of 172 adult patients with COVID-19 were included in the study. All the patients reporting to this hospital were critical. The study included 92 in the death group and 80 in the discharge group. Comparison of various laboratory investigations in death and discharge groups is shown in [Table 1]. [Figure 1] is a box and whisker plot showing kidneys biochemical parameters in two groups. The indicators of AKI including urea (mean 58.5 vs. 37.1, P < 0.05), uric acid (mean 5.67 vs. 4.18, P < 0.05), and blood urea nitrogen (BUN) (mean 26.9 vs. 17.3, P < 0.05) were significantly elevated in the death group compared to discharge group. Death group had significantly elevated total leukocyte count (TLC) (mean 16082 vs. 12100, P < 0.05). This was accompanied by raised levels of interleukin (IL-6) (mean 194.9 vs. 58.7, P < 0.05), C-reactive protein (CRP) (mean 28.45 vs. 9.73, P < 0.05), and ferritin (mean 761.4 vs. 608.2, P < 0.05) in the death group compared to the discharge group.
Table 1: Comparison of various laboratory investigations in death and discharge groups (n=172)

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Figure 1: Box and whisker showing kidneys biochemical parameters in two groups

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Kidney injury and liver injury were analyzed with respect to their relation to mortality, which are presented in [Table 2]. The mortality was found in the patients who had AKI rather than liver injury. The AKI was further correlated with inflammatory markers such as CRP, Ferritin, IL6, d-dimer, and TLC [Table 3].
Table 2: Renal failure and hepatic injury indicators in death and discharge groups (n=172)

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Table 3: Correlation of renal dysfunction and inflammatory markers

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  Discussion Top

The present study found that the mortality in case of the COVID-19 was associated with the presence of AKI. We found that AKI was present significantly in the death group compared to discharge group (P = 0.03). AKI is common among critically ill patients with COVID-19, 76% of patients admitted to ICU presented with AKI, and it is considered a marker of disease severity and a negative prognostic factor for clinical outcomes.[17],[18] In addition, proportion of COVID-19 patients with AKI Stage 3 is higher in ICU admitted patients than non-ICU admissions (56% vs. 32%).[18] After adjustment for demographics, comorbidities, and laboratory values, the risk for death of COVID-19 was higher with AKI than without AKI. Similarly, increased risk of mortality in COVID-19 patients with increased baseline BUN, baseline serum creatine, and peak serum creatine >133 μmol/L was shown.[19] BUN levels in our study were significantly higher in the death group than the discharge (18.4 [15–32.1] vs. 15 [11.1–19.7], P = 0.0004) and the same was true for the Scr levels (0.99 (0.8–1.6) vs. 0.90 [0.8–1.1], P = 0.002). Severe and critical COVID-19 cases are predisposed to renal damage or AKI, mainly indicated by elevated BUN and Scr levels. A prominent relevance between the development of AKI, mortality and kidney-related diseases was reported in hospitalized COVID-19 patients.[19] In a meta-analysis involving 25,278 patients with COVID-19, higher levels of Scr and BUN were associated with severe cases.[20] Thus, high levels of BUN and Scr should be regarded as an important index in the risk stratification of disease severity in COVID-19 patients.

The AKI indicators were correlated significantly with inflammatory markers such as CRP, IL-6, Ferritin, d-dimer, and TLC. Levi et al. reported that the typical indicators of coagulopathy in patients with COVID-19 are an increased D-dimer concentration together with prolongation of the prothrombin time.[21] In the present study, elevated D-dimer was recognized in 48% patients and the mean level of D-dimer was associated with mortality (0.69 [0.39–0.98] vs. 0.32 [0.19–0.48]). A meta-analysis including 5872 COVID-19 patients also found higher D-dimer concentrations were associated with severity and mortality in these patients.[22] However, some previous study involving 127 severe COVID-19 patients did not identify D-dimer as a risk factor for mortality after adjusting according to age for each patient.[23]

CRP level was significantly higher in the nonsurvivors versus discharged COVID-19 patients (18.7 [8.35–41.9) vs. 5.1 [2.4–9.2], P = 0.000]) as also proved by Ruan et al.[24] High serum level of CRP is the key marker of disease progression, a risk factor for mortality of severe COVID-19 patients, along with an indicator of developing cytokine storm in COVID-19 patients.[23],[25] Majority of studies in meta-analysis show a nearly four-fold higher risk of poor outcomes in COVID-19 patients with elevated CRP.[26] The present study obtained elevated Ferritin levels in the nonsurvivor group compared to the discharge group (562.5 [394–1112.7] vs. 460 [327.2–738.2], P = 0.04). Raised ferritin levels have been reported to be one of the predictors of fatality in confirmed COVID-19 cases, suggesting that mortality might be due to virally driven hyper inflammation.[26] Higher ferritin than 500 ng/mL significantly correlated with mortality as Cytokine storm syndrome can cause multi-organ failure and hyperferritinemia.[27],[28] We found an elevated values of IL6 in death group (31.3 [13.9–87] vs. 7.9 [4.3–47.8], P = 0.31). The presence of a systemic inflammatory response in the death group presented with higher levels of IL-6 in nonsurvivors than survivors.[29] All the above significantly elevated inflammatory markers which is the cause of cytokine storm are correlated with AKI.

Bias in the study may be due to selection of cases, as the admission was dependent on severity of disease, bed availability etc., so the patient in the present hospital may be selected lot and differed from the cases in the community. Hence, the findings of the study may be limited to the hospital patients and generalizability may be limited.

  Conclusion Top

Though our study has found association between AKI and mortality, yet we recommend that to confirm the finding of the study and prove causality, the better design study which can established temporality may be conducted.


The authors acknowledge the contribution of Dr. A K Mishra, Director INMAS for helping in the smooth conduct of the data collection.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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