Serum tryptophan and kynurenine levels and risk of heart failure among patients with chronic kidney disease

Background and aims: Chronic kidney disease (CKD) is often complicated by heart failure (HF), leading to increased mortality. Emerging evidence suggests that Tryptophan metabolites, through the Kynurenine pathway (KP), play a significant role in HF pathophysiology. Therefore, we explored the association of Tryptophan (TRP), Kynurenine (KYN), and the Kynurenine to Tryptophan ratio (KTR) with HF in CKD, hypothesizing a link between KP alterations and HF occurrence in this population. Methods: 673 non-dialysis patients aged 30 to 75 with CKD stages 1–5 were included. Incident HF data were collected through medical record reviews, and the median follow-up time was 3.9 years. Serum concentrations of KYN and TRP were measured using High-Performance Liquid Chromatography (HPLC). Results: Patients with more advanced stages of CKD had higher levels of KYN and KTR, and lower levels of TRP (p < 0.001). Following adjustments for age, sex, BMI, hypertension, and hypercholesterolemia, serum KYN and KTR remained significantly associated with prevalent HF in patients with CKD (p = 0.012, p = 0.028 respectively). Furthermore, Cox-regression analysis indicated that KTR concentration was associated with incident HF after adjusting for confounders such as age, sex, BMI, hypertension, hypercholesterolemia and diabetes (p = 0.019). Conclusion: In conclusion, the present analysis suggests that changes in the kynurenine pathway may be a new biomarker for HF in patients with CKD. Thus, KTR concentration might be associated with prevalent and future HF in patients with CKD. Further research is needed to understand the mechanisms and potential of these metabolites in refining HF risk prediction and prevention in CKD patients.