Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe Organ Dysfunction and Mortality in Acute Respiratory Distress Syndrome: A Prospective Observational Study.

Background and aim: Nicotinamide phosphoribosyl transferase (NAMPT) is an upstream cytozyme (cytokine plus enzyme) with unique features, having intracellular NAMPT (iNAMPT) and extracellular NAMPT (eNAMPT) components. Genetic associations and therapeutic inhibition highlight its potential as both a biomarker and therapeutic target. We aimed to study the utility of eNAMPT as a predictor of severe organ dysfunction and its association with mortality in acute respiratory distress syndrome (ARDS). Patients and methods: This is a single-center, prospective observational study involving 90 patients with ARDS. We noted plasma eNAMPT levels, oxygenation levels, inflammatory markers, lung ultrasound scores, driving pressures, and echocardiography parameters. Severity of organ dysfunction and ICU mortality were the outcomes. Results: Plasma eNAMPT was found to be a predictor of severe organ dysfunction in ARDS [adjusted OR: 1.343, 95% CI (1.105-1.634), p-value 0.003]. The cut-off eNAMPT level of ≥ 4.38 ng/mL was used to predict early severe organ dysfunction, with an AUC of 0.752, 95% CI (0.647-0.857), p-value < 0.001, sensitivity of 71.4%, and specificity of 79.2%. Plasma eNAMPT was significantly higher in non-survivors [4.53 (4-9.98) ng/mL] as compared to survivors [3.76 (3.40-4.29) ng/mL] (p-value < 0.001). eNAMPT level ≥4.175 ng/mL was associated with higher mortality (hazard ratio: 3.82; 95% CI: 2.010-7.276, p-value < 0.001) and a shorter median survival time [5 days vs. 16 days (Log-rank (Mantel-Cox) p-value < 0.001]. Conclusion: Plasma eNAMPT (≥4.38 ng/mL) predicts early severe organ dysfunction in ARDS patients. It is also associated with mortality and a shorter median survival time. How to cite this article: Rao S, Srinivas T, Parampalli V, Todur P, Udupa AA, Rao S, et al. Utility of Extracellular Nicotinamide Phosphoribosyl Transferase as a Novel Biomarker in Predicting Early Severe Organ Dysfunction and Mortality in Acute Respiratory Distress Syndrome: A Prospective Observational Study. Indian J Crit Care Med 2025;29(12):1010-1019.