Pre-existing serum indoxyl sulfate and COVID-19 outcomes in patients undergoing hemodialysis: A retrospective cohort study

Abstract

Patients undergoing hemodialysis (HD) are at increased risk of severe complications from COVID-19 due to compromised immune function and comorbidities. This retrospective study aimed to investigate the association between pre-existing serum indoxyl sulfate (IS) concentrations and COVID-19 outcomes in HD patients.
 Methods. Data on pre-existing IS and proinflammatory cytokines, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) were extracted from an existing patient database. The patients were followed up for 1.5 years and compared according to median serum IS concentration: low-IS (< 22.2 μg/mL) and high-IS (≥22.2 μg/mL) groups. The primary outcomes focused on assessing the risk and severity of COVID-19 infection.
 Results. A total of 56 patients aged 62 (56-67) years with a dialysis vintage of 37.5 (30-168) months were included in the analysis. Serum levels of IS were significantly correlated with Kt/V values (p = 0.043), arterial hypertension (p = 0.001), IL-6 (p = 0.023), MCP-1 (p = 0.023), and TNF-α (p = 0.033) concentrations. Elevated serum IS levels were significantly associated with an increased risk of COVID-19 infection (p < 0.0001) and a higher likelihood of hospitalization (p = 0.03). Patients with higher IS levels exhibited more severe lung involvement (p < 0.0001) and a greater need for respiratory support (p = 0.004). A serum IS concentration of 21.5 μg/mL was the optimal threshold for predicting COVID-19 infection in HD patients (sensitivity of 83.4% and specificity of 92.3%, p < 0.0001).
 Conclusion: Our study highlights the detrimental impact of serum IS on COVID-19 infection and its clinical outcomes in patients undergoing HD. Further research is warranted to elucidate the underlying mechanisms and explore potential therapeutic strategies targeting IS in this population.

Hemodialysis dose and long-term COVID-19 outcomes – a retrospective cohort study

“…36 Moreover, our previous report demonstrated that increased preexisting serum indoxyl sulfate was associated with poor COVID-19 outcomes in HD patients, including the severity of pulmonary damage observed on CT scans. 4 Although our study did not directly measure cytokine levels due to its retrospective nature, a notable increase in CRP levels was observed in patients with spKt/V <1.4 compared to those with spKt/V ≥1.4. This finding also implies a potential association between dialysis adequacy and inflammatory markers.…”

“…2,3 Patients undergoing HD are at higher risk of contracting COVID-19 and related complications due to multifactorial risks, including underlying comorbidities, immunosuppression, and frequent dialysis facility visits, which contribute to their increased vulnerability. [2][3][4] Vaccination against SARS-CoV-2 has been found to be highly effective in preventing severe illness, hospitalization, and death in the HD population. 5,6 However, recent studies have suggested that even fully vaccinated individuals, including patients undergoing HD, may still develop long-term COVID, a condition characterized by persistent symptoms that extend beyond the acute phase of COVID-19.…”