Elevated baseline kynurenine independently predicted 60-day mortality (AUC 0.794, p<0.004) and significantly correlated with cardiac dysfunction markers in pulmonary infection and HF patients.
Observational (n=405)
Does kynurenine level predict mortality and correlate with cardiac dysfunction in patients with pulmonary infections and heart failure?
Kynurenine is elevated in pulmonary infections, serves as an independent predictor of 60-day mortality comparable to the SOFA score, and correlates significantly with markers of cardiac dysfunction.
Effect estimate: AUC 0.794
p-value: p=<0.0001
Abstract Backround/Introduction: Tryptophan (Trp) metabolism is essential for regulating immune responses. The kynurenine (Kyn) pathway, a primary route of Trp catabolism, is implicated in inflammatory conditions. For both, pulmonary inflammation as well as cardiovascular diseases an involvement of Kyn in the pathogenesis has been described. However, it remains unclear whether alterations of Trp metabolism due to inflammatory diseases impact the cardiovascular system. Purpose: To characterize alterations in Trp metabolism and evaluate its prognostic significance and association with cardiac function. Methods: A targeted analysis of Trp metabolites using LC-MSMS was conducted on serum of COVID-19 patients (n=116; ARDS=45, Non-ARDS n=71), patients with pulmonary infections excluding COVID-19 (n=67), uninfected individuals (n=114), and a cohort of heart failure (HF) patients (n=108). Results: Patients matched for eGFR, sex, and BMI showed no differences in Trp and Kyn levels, neither in ARDS (p=0.47) nor in those without (p0.99; Figure 1a). This suggests alterations in Trp metabolism to be due to pulmonary infection are independent of SARS-CoV-2. However, we observed a significant change in Trp metabolism in patients with pulmonary inflammation compared to uninfected individuals (Figure 1a,b). Kyn was upregulated in response whereas Trp itself showed reduced serum levels (Figure 1a,b). We then evaluated Kyn as a potential biomarker for mortality. Patients who died within 60 days had higher baseline levels of Kyn compared to survivors. The Kaplan-Meier curve indicated the highest mortality rates among individuals with high Kyn levels (p=0.0001, Figure 1c). Receiver operating characteristics (ROC) analysis revealed an area under the curve (AUC) of 0.794 for Kyn in predicting mortality (Figure 1d), comparable to the AUC of the SOFA score. In multivariate analyses, Kyn remained an independent predictor of mortality (p=0.004, Figure 1e). Furthermore, we found a significant correlation between Kyn and NT-proBNP (r=0.38, p0.0001) in COVID-19 patients. Echocardiographic assessments confirmed an association between Kyn and cardiac dysfunction: left ventricular ejection fraction (LV-EF): r=-0.48, p=0.02; global longitudinal strain (GLS): r=0.55, p=0.02; E/e’: r=0.42, p=0.04. To assess the effect of Kyn on cardiac function in the absence of inflammation, we analyzed tryptophan metabolism in a heart failure cohort and also identified significant correlations between Kyn and NT-proBNP (r=0.24, p=0.03), LV-EF (r=-0.30, p=0.006), GLS (r=0.38, p=0.002), and E/e’ (r=0.31, p=0.006). Conclusion(s): Kyn is elevated in pulmonary infections and holds promise as a biomarker for mortality. Its predictive capacity is comparable to that of the established SOFA score. The association between Kyn and markers of cardiac dysfunction provides valuable insights into underlying mechanisms that may also be relevant in uninfected individuals, particularly those with heart failure.Figure 1
Puetz et al. (Sat,) conducted a observational in Pulmonary infections and Heart Failure (n=405). Kynurenine (biomarker) vs. Low kynurenine levels / uninfected individuals was evaluated on 60-day mortality (AUC 0.794, p=<0.0001). Elevated baseline kynurenine independently predicted 60-day mortality (AUC 0.794, p<0.004) and significantly correlated with cardiac dysfunction markers in pulmonary infection and HF patients.