Factors Affecting Mortality in COVID-19 Patients with Pre-Existing Chronic Kidney Disease

Introduction

The emergence of COVID-19, caused by the novel coronavirus SARS-CoV-2, has triggered a global health crisis since its identification in late 2019. While primarily recognized for respiratory symptoms, the impact of the virus extends across multiple organ systems. Among these, chronic kidney disease (CKD) has surfaced as a notable risk factor for severe COVID-19 outcomes. The interaction between COVID-19 and CKD has raised concerns, as individuals with compromised renal function may face increased vulnerability to severe viral infection, and mortality necessitates a thorough investigation to guide clinical management and public health strategies.

Materials and Methods

All patients presenting with respiratory symptoms and confirmed COVID-19 through real-time polymerase chain reaction (RT-PCR) and having pre-existing CKD between May 2020 and May 2023 were included in the study. Patients already on maintenance hemodialysis and those having chronic heart failure or liver failure were excluded. The study was approved by the Institutional Review Board at All India Institute of Medical Sciences, Patna, number AIIMS/PAT/IEC/2021/752, dated 29/09/2021.

Results

Of the total 150 patients included, 114 (76%) were males. The mean (SD) age of the participants was 59.9 (13.8) years with a majority, i.e., 83 (55.3%) aged more than 60 years, followed by 63 (42%) belonging to the age group of 30–60 years. One hundred and thirty five (90%) of the patients had hypertension while 110 (73.3%) had diabetes mellitus. Among the study participants, only six (4%) had a severe COVID infection. Four (2.7%) had a previous history of renal transplantation. One hundred and twenty two (81.3%) of the patients required hemodialysis during their hospital stay, and 83 (55.3%) developed acute kidney injury (AKI). Forty six (30.7%) of the participants survived and were subsequently discharged, while 104 (69.3%) died [Table 1].

On Kaplan–Meier Curve analysis, it was seen that the median survival time in patients who developed AKI was 11 (95% CI: 8.639–13.361) days while the median survival time in patients who did not develop AKI was 12 (95% CI: 6.637–17.363) days. Although visual inspection of the curves shows a steeper curve for the patients who developed AKI [Figure 1], the Log rank test revealed that there was no significant difference between the curves [Chi-square=1.098 (at 1 degree of freedom) and P=0.30].

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Figure 1:

Kaplan–Meier curves of patients with chronic kidney disease and acute-on-chronic kidney disease.

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Univariate cox regression analyses were carried out, and it was seen that male gender, age, requirement for invasive ventilation, increase in total leukocyte count (TLC), lactate dehydrogenase (LDH), C-reactive protein (CRP), D-dimer, and IL-6 levels significantly increased the hazard of death, while the number of total hemodialysis, number of conventional hemodialysis, lymphocytosis, and increased platelet count decreased the hazard of death [Table 2].

Discussion

In our study, there was a significant rise in D-dimer levels in nonsurvivors of COVID-19, consistent with findings reported by Tang N. et al.¹ This elevation may be attributed to disseminated intravascular coagulation (DIC) caused by sepsis. In sepsis, endothelial cells and monocytes release cytokines, causing free thrombin circulation and platelet activation, indicating activation of the common coagulation pathway.¹ The higher hazards ratio for invasive ventilation signified the critical status of patients necessitating invasive ventilation and increased mortality.

We observed that 55.3% of CKD patients with COVID-19 developed AKI, which may be attributed to the direct infection mechanism of the virus. SARS-CoV-2 enters cells through angiotensin converting enzyme (ACE 2), and as it circulates systemically, the kidneys—abundant in ACE 2—emerge as a potential site for viral entry, potentially causing AKI.²

In our study, older male participants faced a heightened mortality risk, potentially linked to higher ACE 2 levels in elderly males.³ Notably, factors like smoking, not considered in our study, may also contribute to decreased male immunity, further escalating their risk of mortality. Age demonstrated a 1.018-fold hazard increase per year in CKD patients, which may be because of compromised viral control and prolonged proinflammatory responses.⁴

Interestingly, it was observed that lymphocytosis was a protective factor with a hazard ratio of 0.9, while an increase in the TLC was found to increase the hazard of death. This may be due to the fact that lymphopenia has been frequently associated with severe COVID-19 infection.⁵ Several potential mechanisms have been proposed to elucidate this connection. These mechanisms encompass direct lymphocyte inhibition, destruction of lymph nodes, the release of cytokines, suppression of lymphocytes due to lactic acidosis, and the attachment of the virus to the ACE 2 receptors on lymphocytes.⁶

Factors such as male gender, advanced age, elevated inflammatory markers, and the necessity of invasive ventilation were associated with an increased risk of mortality in COVID-19 patients with coexisting CKD.