Prospective Analysis of Tryptophan Metabolites in COVID-19 patients with CKD

Introduction: Chronic kidney disease (CKD) is associated with accelerated tryptophan (TRP) catabolism and accumulation of bioactive TRP metabolites due to both inflammation and impaired kidney function. In COVID-19 patients, increased release of proinflammatory cytokines likely activates indoleamine 2,3-dioxygenase, leading to TRP degradation along the kynurenine pathway. However, changes in TRP metabolites in COVID-19 patients with CKD remain unknown.

Objective: To measure the concentrations of TRP and its bioactive metabolites in COVID-19 patients with impaired kidney function over time.

Methods: We collected demographic, clinical, and serum samples from adult participants with confirmed SARS-CoV-2 infection and impaired kidney function enrolled in the NIH RECOVER adult protocol. Baseline serum creatinine at enrollment was used to calculate estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, categorizing participants as controls (n=24, eGFR ≥90 mL/min/1.73 m²) or CKD (n=42, eGFR ≤89 mL/min/1.73 m²). Follow-up serum samples were obtained at 24 months. TRP, kynurenic acid, and anthranilic acid were quantified using liquid chromatography-tandem mass spectrometry employing validated methods.

Results: At baseline, serum TRP levels were significantly lower in the CKD group compared to controls (82.71±35.44 µM vs 109.7±33.50 µM, p=0.004). In the CKD group, baseline hs-CRP correlated significantly with anthranilic acid (r= -0.28, p=0.04). At 24 months, kynurenic acid levels were significantly higher in the CKD group than in controls (37.86±36.82 µM vs 21.34±15.47 µM, p=0.049). At 24 months, significant associations were observed in the CKD group only: eGFR with kynurenic acid (r= -0.52, p=0.0004) and with the TRP/kynurenic acid ratio (r=0.43, p=0.004).

Conclusion/Discussion: These preliminary findings demonstrate a significant decline in serum TRP levels in COVID-19 patients with CKD and show inverse associations between eGFR and kynurenic acid in this group. Ongoing analyses of additional TRP metabolites including kynurenine, 3-hydroxykynurenine, quinolinic acid, picolinic acid, and 3-hydroxyanthranilic acid will help clarify the role of individual TRP metabolites in CKD progression in these patients.

Key Topics:

• Clinical assessment and pathogenesis of clinical manifestations
• Long-term follow-up of the RECOVER Cohorts