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Utility of Circulating Extracellular Nicotinamide Phosphoribosyltransferase and Its Association with Acute
Thejesh Srinivas1, Gagana Hanumaiah2, Danavath Nagendra1
1Department of Critical Care Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Aims And Background:
Acute respiratory distress syndrome (ARDS) is a complex clinical condition lacking reliable biomarkers that reflect underlying biological injury and predict clinical outcomes. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), an upstream inflammatory mediator implicated in endothelial injury, has emerged as a potential biomarker in ARDS. However, its association with ARDS onset and mortality has not been systematically synthesized. This review aimed to evaluate the association between circulating eNAMPT levels, ARDS onset, and mortality through a systematic review and meta-analysis.
Materials And Methods:
This systematic review and meta-analysis, compliant with Preferred Reporting Items For Systematic Reviews And Meta-Analyses (PRISMA)-2020 guidelines, was registered in PROSPERO (CRD420251229714). PubMed, Scopus, Embase, and the Cochrane Library were searched from database inception to 22 December 2025. Studies measuring circulating eNAMPT levels in adult ARDS populations were included. Random-effects models were applied to pool standardized mean differences (SMDs) to assess associations with ARDS onset (ARDS vs controls) and mortality (non-survivors vs survivors). Heterogeneity was assessed through subgroup and sensitivity analyses.
Results:
Six studies comprising 1,061 participants, including 665 ARDS patients, were included. Circulating eNAMPT levels were significantly elevated in ARDS cases compared with healthy controls [SMD = 1.07, 95% confidence interval (CI) = 0.41-1.74; p-value = 0.0016], although substantial heterogeneity was observed (I² = 91.1%). Descriptive pooled estimates showed mean eNAMPT concentrations of 49.58 ng/mL in ARDS vs 7.30 ng/mL in controls. Elevated eNAMPT levels were also significantly associated with increased mortality among ARDS patients (SMD = 0.39, 95% CI = 0.19-0.59; p-value = 0.0001) with minimal heterogeneity (I² = 1.4%). Subgroup analyses demonstrated consistent mortality associations across Western and Asian cohorts.
Conclusion:
Circulating eNAMPT is associated with ARDS and, more importantly, reflects disease severity, serving as a biologically informative biomarker of inflammatory and endothelial injury rather than serving as a standalone diagnostic marker.
Clinical Significance:
These findings underscore the potential of eNAMPT for biomarker-guided risk stratification and for informing precision therapeutic strategies targeting upstream inflammatory pathways in ARDS.
How To Cite This Article:
Srinivas T, Hanumaiah G, Nagendra D, Chaudhuri S, Vasudeva A, Rao S, et al. Utility of Circulating Extracellular Nicotinamide Phosphoribosyltransferase and Its Association with Acute Respiratory Distress Syndrome Onset and Mortality: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2026;30(8):686-697.
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