INTRODUCTION
As of November 13, 2021, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has affected more than 2,510,000 individuals and caused 5,000,000 deaths worldwide.[1] Other than being a respiratory pathogen, the SARS-CoV-2 has a predilection for the kidneys. Various studies with their data accumulating over time showed that, although SARS-CoV-2 infection primarily causes acute respiratory illness, other organs may also be involved by the virus such as the kidney and cause complications.[2] 5%–15% of the COVID-19 cases had renal involvement and showed a high mortality of 70%–90%, as recorded in SARS-CoV-2 and Middle East respiratory syndrome coronavirus epidemics.[3,4]
Kidney Disease: Improving Global Outcomes (KDIGO) has defined acute kidney injury (AKI) as an increase in the serum creatinine of 0.3 mg/dl over a 48-h period or 50% increase in baseline creatinine.[5] SARS-CoV-2 acts by binding itself to the angiotensin-converting enzyme 2 receptors. These receptors are found to be present greater in the kidney when compared to that in the lungs.[6,7] They are expressed on the brush border apical membrane of the proximal tubule and are also present in the podocytes.[7] However, the impact of AKI may differ from place to place depending on the health-care systems, socioeconomic status of the patients, education status of the patient, and geography of the locality. Several mechanisms are involved in the pathogenesis of AKI in COVID-19, including direct virus invasion, immune dysfunction, abnormal coagulation, sepsis, drugs, and underlying diseases.[8]
Patients with underlying comorbidities such as diabetes mellitus (DM), hypertension (HTN), and even chronic kidney disease (CKD) have been found to have a poorer outcome in COVID-19. As such, it was found that CKD patients not undergoing hemodialysis exhibited a vulnerability to COVID-19 disease when compared to that of patients on renal replacement therapy (RRT).[9] The information regarding the development of AKI in patients with COVID-19 is still building up and not completely explored. Thus, in this study, we aim to determine the parameters of renal function, i.e., urea and creatinine and to correlate their levels with the outcome of the COVID-19 patients.
Objectives
- To determine the incidence of AKI in COVID-19
- To correlate AKI with the outcome of the COVID-19 patients.
MATERIALS AND METHODS
This study has been conducted in a hospital in Bengaluru, Karnataka, India, after obtaining ethical clearance from the Institutional Ethics Committee (No: 532/L/11/12/Ethics/ESICMC and PGIMSR/Estt. Vol. IV).
The case files of the 200 patients admitted to the Department of General Medicine Triage and COVID Ward/intensive care unit (ICU) at ESICMC and PGIMSR during the period of August 2020–July 2021, fulfilling the inclusion criteria were analyzed and appropriate data were collected after obtaining consent from these patients.
Case record form with follow-up chart was used to record the duration of disease, history of treatment, and complications. COVID-19 infection was be diagnosed by either Reverse Transcriptase – Polymerase Chain reaction Reverse Transcriptase – Polymerase Chain reaction (RT-PCR) or rapid antigen test (RAT) technique. Patients underwent biochemical investigations which included complete blood count, liver function test, renal function test, serum electrolytes, serology, C-reactive protein, lactate dehydrogenase, D-dimer, arterial blood gas, and Chest X-ray. Comorbid conditions such as metabolic disorders, endocrine disorders, renal disorders, cardiac disorders, and respiratory disorders were confirmed with the past medical history.
Inclusion criteria
Adult patients (aged 18 years and above) with either RT-PCR or RAT positive for COVID-19 admitted to the Department of General Medicine Triage and COVID Ward/ICU at ESICMC and PGIMSR during the period of August 2020–July 2021 and willing to give written informed consent for participation were included in the study.
Exclusion criteria
The following were excluded from the study:
- Patients who were unwilling to participate in the study
- Patients aged <18 years
- Drug-induced AKI
- Known case of CKD.
The patients were monitored and the outcome was measured either as improved (clinical improvement, decreasing trend of inflammatory markers, and discharge) or deteriorated (clinically worsening, increasing trend of inflammatory markers, and death of the patient). The patients were discharged as per the discharge policy of the Government of Karnataka after 10 days of symptom onset with no fever or symptoms for 3 consecutive days, maintained oxygen saturation above 95% for 4 consecutive days, showed improvement clinically with no breathlessness, showed a decreasing trend of inflammatory markers and repeat RT-PCR test turned negative.
Method of statistical analysis
Statistical Package for the Social Sciences (SPSS) version 18.0 (Chicago SPSS, Inc). Categorical data were represented in the form of frequencies and proportions. Chi-square test was used as a test of significance for qualitative data. Continuous data were represented as mean and standard deviation. Pearson correlation was done to find the correlation between two quantitative variables and qualitative variables, respectively. P < 0.05 was considered significant. Creatinine levels were noted and the baseline creatinine value of 0.9 mg/dl and lower was considered to be normal. Patients were diagnosed with AKI (the primary endpoint) as per the KDIGO guidelines.[5] with the repeat creatinine value which was checked after 7 days.
RESULTS AND ANALYSIS
As seen in Table 1, most of the cases enrolled for the study are above the age of 50 years, i.e., 57%. Of the 200 included in the study, 117 are male and 83 are female.
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Table 1: Age and Sex Distribution
170 of the 200 patients were discharged in hemodynamically stable condition, whereas the remaining 30 succumbed to death as seen in Table 2.
Table 2: Demographic data
HTN was present in 40% of the patients who were discharged and 36.67% of the patients who died, whereas DM was present in 40.59% and 33.33% of patients who were discharged and died, respectively. Thus, we see that HTN and DM are the major comorbidities in the study population as depicted in Table 3.
Table 3: Data on Comorbidities
In the present study, the mean urea levels were 37.82 ± 23.68 mg/dl and mean creatinine values were 0.95 ± 0.85 mg/dl as depicted in Table 4.
Table 4: Laboratory parameters
In Table 5, we see that the urea levels among those who were discharged and died were 35.98 ± 20.27 mg/dl and 52.22 ± 38.01 mg/dl, respectively, and this was statistically significant with a P = 0.00.
Table 5: Comparing the laboratory parameters between the discharged cases and to those who died
The creatinine levels were 0.88 ± 0.44 mg/dl and 1.32 ± 1.76 mg/dl among the COVID-19 patients who got discharged and died, respectively, with a P value of 0.00 as well and this too was statistically significant.
Of the 200 study participants, 59 (29.5%) developed AKI. As depicted in Table 6, we see that the percentage of the COVID-19 patients who developed AKI among those who were discharged is 25.88% when compared to those who died which is 50.0% and this difference is statistically significant with a P = 0.01.
Table 6: Involvement of the kidney
DISCUSSION
Higher in-hospital mortality is an important complication of AKI in COVID-19 and AKI serves as an important prognostic marker of survival and disease severity.[10,11] The severity of AKI was also related to the mortality rate. Patients requiring higher intensive care support have a higher incidence of AKI[12–14] with 13.3%–35.2% of patients with a critical disease requiring kidney replacement therapy (KRT).[14–16]
Hypovolemia, a risk factor for the development of AKI, is a common occurrence in early COVID-19 and hence it is critical to individualize the fluid management.[17] It was demonstrated in a randomized clinical trial that fluid and vasopressor resuscitation in patients with septic shock based on dynamic hemodynamic assessment may reduce the risk of AKI and respiratory failure.[18]
In the present study, we see that 25.88% of the patients who were discharged developed AKI when compared to 50.0% among those who died and this difference is statistically significant with P = 0.01. Chan et al. (January 2021) concluded that AKI was more common among the hospitalized COVID-19 patients and was associated with higher mortality. Moreover, only 30% of the patients with AKI survived with the recovery of renal function by the time of discharge.[19]
In the present study, DM was a major comorbid condition being present in 40.59% and 33.33% of patients who were discharged and died, respectively. Lim et al. found that comorbid diabetes was more common in AKI patients with COVID-19 than in the non-AKI group (46.7% vs. 27.7%, P = 0.04).[20]
The management of AKI in COVID-19 is not significantly different from that of other causes of AKI. AKI can be prevented by strategic early fluid management in hypovolemia or fluid and vasopressor resuscitation in septic shock.[21] The goals of management in COVID-19 patients who already have AKI should be to improve the patient outcomes and prevent worsening of kidney function. The management includes avoiding nephrotoxic drugs, optimization of hemodynamics to correct hypovolemia or hypervolemia, management of blood glucose and standard care in multiorgan failure and shock.[21] The treatment modalities in COVID-19 encompass a variety of nephrotoxic medications and this puts them at a higher risk for AKI, making drug stewardship extremely important. It is important to provide optimal resources for RRT and to begin appropriate RRT modality with the right dose at the right time in those requiring RRT. As there are several mechanisms involved in the pathogenesis of AKI in patients with COVID-19, various treatment modalities targeting these mechanisms such as adoptive T-cell therapy, anticoagulation therapy, and receptor antibodies, need more attention and are an evolving area of research.
The longitudinal effects of COVID-19-associated AKI on kidney function remain largely unknown. Nugent et al. noted in their study that estimated glomerular filtration rate declined by 11.3 mL/min/1.73 m2 per year faster in patients with COVID-19-associated AKI compared with patients with AKI not associated with COVID-19.[22] This emphasizes the need to monitor kidney function after hospital discharge among patients with COVID-19-associated AKI.
Limitations
The study is however not without any limitations. This study was conducted in a single center and the sample size was small.
CONCLUSION
The COVID-19 patients who had developed AKI at the time of presentation had a poor prognosis as well as increased risk of mortality.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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