Outcomes of patients with end-stage kidney disease hospitalized with COVID-19: A single-center experience from Eastern India

Aruna Acharya; Haladhar Naik; Rohit Gaude

doi:10.4103/jhrr.JHRR_21_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 1 | Page : 22-29

Outcomes of patients with end-stage kidney disease hospitalized with COVID-19: A single-center experience from Eastern India

Aruna Acharya¹, Haladhar Naik², Rohit Gaude¹
¹ Department of Nephrology, SCB Medical College and Hospital, Cuttack, Odisha, India
² Department of Surgery, SCB Medical College and Hospital, Cuttack, Odisha, India

Date of Submission	18-Nov-2021
Date of Acceptance	28-Jan-2022
Date of Web Publication	20-May-2022

Correspondence Address:
Aruna Acharya
Department of Nephrology, SCB Medical College, Manglabag, Mangalabag, Cuttack 753007, Odisha
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jhrr.JHRR_21_21

Abstract

Aim: This study aimed to describe the clinical characteristics, survival outcome, and its correlation with biochemical parameters in coronavirus disease-2019 (COVID-19)-infected patients with end-stage kidney disease (ESKD). Materials and Methods: A prospective observational study was on hospitalized patients with confirmed COVID-19 infection from September 1, 2020 to October 31, 2020. Data related to demographics, baseline history of comorbid conditions, dialysis-specific data, details on hospital admissions, COVID-19 treatment regimen, laboratory investigations, computed tomography (CT) severity score, COVID-19 Reporting and Data System score, and clinical outcomes (improved/death), duration of hospital stay, oxygen/vasopressor support were collected. Results: A total of 216 ESKD patients with COVID-19 infection were included in this study. The median age was 48.0 years (74.5% men, 25.5% women). Severe acute respiratory infection (44.7%), hypertension (28.2%), and type 2 diabetes mellitus (22.4%) were the most common comorbidities. Elevated levels of serum creatinine (9.3 mg/dL) and blood urea nitrogen (84.8 mg/dL) were observed in the patients with COVID-19 infection. The change in mean levels of serum creatinine and estimated glomerular filtration rate from baseline to post-treatment was significant (0.9 [95% CI: 0.7, 1.1; P < 0.001] and 3.4 [95% CI: 3.2, 3.6; P < 0.001], respectively). Approximately, 79.6% (n = 172) of patients improved post-treatment. Serum creatinine (1.786, 95% CI: 1.031, 3.095; 0.039) and ferritin levels (51.959, 95% CI: 7.901, 341.685; P < 0.001) remained significantly and independently associated with survival. The median time to clinical survival was 17.0 days. Conclusion: Serum creatinine and ferritin levels were independently associated with survival.

Keywords: Blood urea nitrogen, serum creatinine, severe acute respiratory infection, survival

How to cite this article:
Acharya A, Naik H, Gaude R. Outcomes of patients with end-stage kidney disease hospitalized with COVID-19: A single-center experience from Eastern India. J Health Res Rev 2022;9:22-9

How to cite this URL:
Acharya A, Naik H, Gaude R. Outcomes of patients with end-stage kidney disease hospitalized with COVID-19: A single-center experience from Eastern India. J Health Res Rev [serial online] 2022 [cited 2023 Jun 7];9:22-9. Available from: https://www.jhrr.org/text.asp?2022/9/1/22/345550

Introduction

The severe acute respiratory syndrome coronavirus 2 infection causes a novel coronavirus disease-2019 (COVID-19). It is implicated to cause multiorgan failure including kidney. It may also be presented asymptomatically without organ manifestations.^[1] End-stage kidney disease (ESKD) is important predictive risk factors for COVID-19 progression. On the contrary, emerging data suggest that elderly patients with several underlying cardiometabolic comorbid conditions such as diabetes, hypertension, obesity, chronic obstructive pulmonary disease, and heart failure are known risk factors of COVID-19 infection which lead to subsequent poor outcomes.^[2],[3]

Several hospital-based studies conducted worldwide have emphasized the potential role of acute kidney injury (AKI) in increasing the mortality risk among COVID-19-infected patients.^[4] Various reports have revealed that higher incidence of hyperfibrinogenemia, hyperferritinemia, elevated D-dimer, and C-reactive protein (CRP) levels, lymphopenia, and anemia occurred in dialyzed ESKD patients with COVID-19.^[5],[6],[7] In addition, such abnormalities in biochemical biomarkers have been shown to be associated with severity and mortality outcome in patients with COVID-19.^[7] Therefore, early evaluation and monitoring of both liver and kidney functions, as well as hematologic parameters, are pivotal for predicting the progression of COVID-19.^[8]

It is important to understand the outcomes of COVID-19-infected patients with ESKD which would help risk-stratify patients with ESKD to certain therapies for COVID-19 at the time of hospitalization. Recent studies have reported that compared to general population, mortality rate was higher among patients with ESKD infected with COVID-19.^{[2],[7],[9],[10]} In addition, increased age, comorbidities including diabetes, hypertension, and cardiovascular disease, elevated levels of inflammatory markers are significantly associated with disease severity and in-hospital mortality in this population.^[2],[11] However, Indian studies evaluating survival outcomes among ESKD patients with COVID-19 are scarce. Therefore, this study aimed to assess the survival outcome and its correlation with biochemical parameters in ESKD patients with COVID-19 from Eastern India.

Materials and Methods

Study design and settings

This prospective observational study was conducted on hospitalized patients with confirmed COVID-19 infection at the Department of Nephrology, SCB Medical College, Cuttack, Odisha from September 1, 2020 to October 31, 2020. The study was conducted in accordance with ethical principles that are consistent with the Declaration of Helsinki. The study protocol was approved by Institutional Review Board/ Ethics Committee.

Inclusion and exclusion criteria

All ESKD patients (age ≥11 years) who were tested positive by polymerase chain reaction testing of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 ribonucleic acid (RNA) were eligible. The patients were followed up through December 12, 2020. Diagnosis of ESKD was done using International Classification of Diseases guidelines for testing.^[12] The exclusion criteria were patients with pregnancy, malignancy, active tuberculosis, bacterial/fungal infection, and AKI at admission, or patients under immunosuppression.

Data collection

Data related to patient demographics included age, sex, anthropometric measurement (height, weight, and body mass index calculations), baseline history of comorbid conditions, dialysis-specific data, details on hospital admissions, COVID-19 treatment regimen (steroids/antimalarial/antipyretic/antibacterial/antiviral), laboratory investigations (serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), CRP, D-dimer, and ferritin), CT severity score (CT-SS), COVID-19 Reporting and Data System (CO-RADS) score, and clinical outcomes (improved/death), duration of hospital stay, oxygen/vasopressor support within 48 h of hospital admission were collected.

Distribution of disease

CT chest findings^[

13]

The CT chest findings were the presence of ground-glass opacity, the crazy-paving pattern of thickened interlobular septa and intralobular lines, consolidation, reticular pattern, subpleural curvilinear line, air bronchogram, bronchial wall thickening and bronchiectasis, vascular dilation, pleural changes, halo sign, reversed halo sign, fibrosis, lymphadenopathy (mediastinal and hilar lymphadenopathy).

CO-RADS score based on the CT findings

Based on CT findings the level of suspicion of COVID-19 infection was graded from CO-RADS 1 to CO-RADS 5 score. CO-RADS 1: CT is normal, or these findings are indicating a non-infectious disease with a very low level of suspicion for COVID-19; CO-RADS 2: CT findings are consistent with infection other than COVID-19 and it signifies a low level of suspicion for COVID-19; CO-RADS 3: CT abnormalities indicate infection but are indeterminate or atypical findings based on CT features alone; CO-RADS 4: CT abnormalities which signify a high level of suspicion for COVID-19 indicate infection with unilateral ground-glass or multifocal consolidations; and CO-RADS 5: signifies a very high level of suspicion for COVID-19. Obligatory features include ground-glass opacities, with or without patchy consolidations, multifocal and bilateral distribution.

Definition^{[

14],[

15]}

Mild COVID-19 infection was defined as symptomatic patients with CT-SS of ≤7.

Moderate COVID-19 infection was defined as patients with pneumonia with CT-SS of 8–17.

Severe COVID-19 infection was defined as patients with clinical signs of pneumonia with CT-SS of ≥18.

Treatment regimen

The conservative medical treatment consisted a combination of multivitamins (vitamin C, vitamin D, vitamin B), analgesics (intravenous dose of paracetamol), antibiotic (either piperacillin + tazobactam [2.25 mg], doxycycline [100 mg], meropenem [1 g]), and other medications (enoxaparin [0.4 mg], hydroxychloroquine [400 mg], and ivermectin [12 mg]) were provided for mild to severe patients. Patients with moderate severity were given intravenous dexamethasone (8 mg). Antiviral therapy of favipiravir (200 mg) was administered in moderate patients. If moderate patients progressed to severe stage, then 1–2 mg/kg intravenous dose of methylprednisone was administered. Antiviral therapy of remdesivir was administered in severe patients without any baseline liver disorder and those who gave written consent before starting the therapy. Patients were assigned to intravenous 200 mg dose of remdesivir dose on day 1 followed by 100 mg dose on days 2–5 in single daily infusions.

Endpoints

The primary outcome was to describe COVID-19 associated survival in patients with ESKD. The secondary outcome was to determine covariates of biochemical parameters associated with survival.

Statistical analysis

Data were analyzed using Statistical Package for the Social Sciences (SPSS) software program, version 23.0. Descriptive statistics was used to describe categorical variables (frequency and percentages) and continuous variables (mean and standard deviation [SD] or median and range [depending on the normality of data]). The paired non-parametric Wilcoxon signed-rank test was used to compare variables pre- and post-treatment. Survival analysis was performed using a univariate regression method. Covariates with a P < 0.05 in the univariate analysis were included in the multivariate regression model. The Kaplan–Meier plots were used to analyze time-to-event outcomes (clinical survival). A value of P < 0.05 was considered statistically significant.

Results

Clinical characteristics

A total of 216 patients with ESKD were diagnosed with COVID-19 during the 9-week study period. Of these, 161 were men (74.5%), and 55 were women (25.5%) with their ages ranging from 11 to 88 years (average age, 48.0 years). The majority of patients belonged to the age group of ≥41 to ≤60 years (51.4%) followed by the age group ≥11 to <40 years (34.7%) and age group ≥61 years (13.9%). The average BMI was 25.8 kg/m². Severe acute respiratory infection (44.7%), hypertension (28.2%), and type-2 diabetes mellitus (22.4%) were the most common comorbidities followed by, hepatitis (11.8%), influenza-like illness (5.9%), uremic encephalopathy (5.9%), AKI (3.5%), and anemia (3.5%). The mean duration of dialysis was 8.0 months and ranged from 1.0 to 24.0 months. Results of baseline laboratory tests at the time of admission are summarized in [Table 1]. Patients showed elevated levels of serum creatinine (9.3 mg/dL) and BUN (84.8 mg/dL) at the time of admission. The average eGFR was abnormal (7.5 mL/min).

Table 1: Demographic characteristics

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Posttreatment laboratory result

The serum creatinine level improved after the initiation of treatment. The pre-treatment median serum creatinine level was 9.3 mg/mL which declined post-treatment to 8.4 mg/dL. However, the mean BUN and eGFR levels worsened during hospitalization (87.9 mg/dL and 4.1 mL/min, respectively) [Table 2].

Table 2: Biochemical findings and outcomes

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Change in laboratory parameters

The mean levels of serum creatinine and eGFR showed a remarkable reduction from baseline to the post-treatment with a mean difference of 0.9 (95% confidence interval [CI]: 0.7, 1.1; P < 0.001) and 3.4 (95% CI: 3.2, 3.6; P < 0.001) [Figure 1]A and C. However, the mean levels of BUN levels were significantly elevated from baseline to the post-treatment with a mean difference of –3.1 (95% CI: –5.0, –1.2; P = 0.002) [Figure 1]B.

Figure 1: Change in biochemical parameters. Change in (A) serum creatinine, (B) BUN and (C) eGFR. Data shown as mean difference (95% CI); P value. BUN = blood urea nitrogen, CI = confidence interval, eGFR = estimated glomerular filtration rate

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Outcomes

The moderate group (CT-SS of 8–17) was consisted of 144 patients, whereas the severe group (CT-SS of ≥18–25) was composed of 72 patients. The average CT-SS was 16.4. Total 69.4% of patients received oxygen support, whereas 35.2% of patients were on machinal ventilation. Nearly 79.6% (n = 172) of patients improved post-treatment, whereas 20.4% (n = 44) of patients died. The median length of hospital stay was 9.0 days [Table 2].

Prognostic factors associated with survival

Prognostic factors associated with survival by univariate and multivariate regression analysis are depicted in [Table 3]. By univariate regression analysis serum creatinine, D-dimer, and ferritin levels were associated with improved survival outcomes in ESKD patients with COVID-19 (P < 0.05). Similarly, by multivariate analysis serum creatinine (1.786, 95% CI: 1.031, 3.095; 0.039) and ferritin levels (51.959, 95% CI: 7.901, 341.685; P < 0.001) remained significantly and independently associated with survival [Table 3].

Table 3: Covariates of biochemical parameters associated with survival

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Clinical survival

The median (95% CI) time to clinical survival was 17.0 (13.3, 20.7) days [Figure 2].

Figure 2: Kaplan–Meier plot for survival

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Discussion

This study examined the clinical features, biochemical parameters, treatment strategies, and survival outcomes of ESKD patients infected with COVID-19. The salient observations of this study are as follows: (a) male preponderance in the overall study population; (b) severe acute respiratory infection, hypertension, and type-2 diabetes mellitus were the predominant comorbid conditions; (c) incidence of elevated serum creatinine and BUN were more common in ESKD patients with COVID-19 infection; (d) a significant reduction in serum creatinine and eGFR post-treatment; (e) serum creatinine, D-dimer, and ferritin levels were significantly associated with survival.

A previous nationwide study from the USA that evaluated COVID-19 prevalence in patients with ESKD, involved a large population (n = 31,509). The key observation was the higher prevalence of COVID-19 in patients of age group 45–64 years (40.5%) as compared to an older adult (65–79 years, 35.9%) and oldest population (≥80 years, 12.1%).^[16] Kang et al.^[17] also showed COVID-19 was the predominant among adult patients aged ≤60 years with ESKD than older patients aged >60 years (n = 5459 vs. 1868). Evidence from studies that included the Indian population showed corroborating observations.^[18],[19] In parallel to these studies, this study revealed that the prevalence of COVID-19 was found to be highest in adult patients (≥41 to ≤60 years; 51.4%). Therefore, the aforementioned studies revealed that the adult population with ESKD are at higher risk of developing COVID-19.

The previous study from India of 131 COVID-19 patients from the ESKD population, 76.0% of patients had HTN and 29.0% of patients had T2DM.^[20] Subsequently, a multicentric study showed that HTN (73.3%) and diabetes (52.0%) were the most prevalent comorbidities observed among the study population.^[15] A retrospective study from India (n = 37) reported that half of the patients with COVID-19 had diabetes and hypertension.^[21] Similarly, this study also reported that severe acute respiratory infection, HTN, and T2DM as common comorbid conditions to be observed in ESKD patients with COVID-19. Likewise, these patients, with several underlying conditions are more susceptible to develop AKI worse COVID-19 outcomes.^[22],[23]

The severity of viral infection can lead to either increase or decrease in some blood count parameters as markers of mortality. The higher incidence of elevated levels of serum creatinine and BUN among the ESKD patients with moderate to severe COVID-19 infection is in accordance with the previous studies across the globe.^[24],[25] Ng et al.^[26] reported high incidence of elevated BUN (51.0 vs. 18.0 mg/dL), serum ferritin (2491.5 vs. 780.0 ng/mL), and lymphopenia (0.7 vs. 0.9 1000/μL) in patients with ESKD compared to those with non-ESKD. Similarly, another study from China showed a higher prevalence of elevated D-dimer, BUN, creatinine levels in COVID-19-infected patients with ESKD. These findings suggest that BUN and serum creatinine may be useful biomarkers for assessing future incidences of unfavorable outcomes associated with COVID-19 in dialysis patients.

This study showed the efficacy of a conservative management strategy in improving serum creatinine to normal level. Further, comparable BUN and eGFR levels were worsened from baseline to post-treatment. However, there are no randomized controlled trials have been published effective therapies for COVID-19 patients on maintenance dialysis. It is interesting to note that a study by Wang et al.,^[24] that included 116 chronic kidney disease (CKD) patients with mild and severe COVID-19 infection, reported comparable improvement in BUN and serum creatinine in patients with CKD from baseline to post-treatment (pre- vs. post-treatment: 32.1 vs. 31.9 mmol/L; P = 0.981 and 937.6 vs. 914.3 μmol/L; P = 0.801). Similarly, Zhang et al.^[27] studied the effect of symptomatic support therapy on five kidney transplant recipients with COVID-19. The study showed that baseline BUN and creatinine were improved after immunosuppressive medications.

The length of hospital stay (9.0 days) reported in this study was in accordance with the previous studies. In a study by Sachdeva et al.,^[28] the median duration of ICU stay was 9 days (range: 2–23 days). Conversely, Rastad et al.^[29] reported a relatively lower median length of hospital stay (2 [IQR: 0–5] days) as compared to this study.

Previous nationwide analysis from Turkey that survival rates were higher in ESKD patients with COVID-19 (81.7%).^[30] On the parallel lines, this study reported a similar survival rate (79.6%). Mortality was observed in a total 20.4% of patients. Among these, overall deaths the proportion of male patients (84.1%) was more than female patients (15.9%), out of 14 patients, four patients had the presence of ≥2 comorbidities. Tortonese et al.^[31] showed that the survival rates were comparatively lower in patients with COVID-19 on maintenance dialysis (67.9%).

The most common characteristics of severe COVID-19 patients included elevated levels of serum CRP, serum creatinine, procalcitonin, D-dimer, and hyperferritinemia.^[32] Regression analysis showed that improved levels of serum creatinine and BUN level were independently associated with survival.

Limitations

Several limitations of this study should be acknowledged. First, this was a single-center, single-arm study and limited enrolled patients therefore, these observations cannot be generalized to the overall Indian population. Second, the data did not include interleukin 6 which might be associated with COVID-19 severity and mortality. Other limitations include the inability to assess out-of-hospital deaths and missed number of dialysis sessions due to lockdown.

Conclusion

In this study, a survival rate of COVID-19 was higher in ESKD patients. The use of clinical and biological parameters as early prognostic markers will be helpful to guide future management strategies. Effective intervention might be a benefit in reducing mortality among dialysis patients with severe COVID-19 infection. Serum creatinine and BUN levels were significantly associated with survival.

Acknowledgement

None.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authors’ contributions

AA, HN, and RG contributed to concepts, design, definition of intellectual content, clinical studies, data analysis, manuscript editing, and manuscript review. AA contributed to literature search, statistical analysis, manuscript preparation, and guarantor.

Ethical policy and institutional review board statement

The study was approved by Institutional Ethics Committee and study procedure was in accordance with the principles of the Declaration of Helsinki.

Patient declaration of consent

Not applicable.

Data availability statement

Data availability within the article or its supplementary materials.

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