Circulating RIPK3 levels are associated with mortality and organ failure during critical illness.

Autor:	Ma KC; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine.; NewYork-Presbyterian Hospital., Schenck EJ; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine.; NewYork-Presbyterian Hospital., Siempos II; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine., Cloonan SM; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine., Finkelsztein EJ; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine., Pabon MA; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine.; Division of General Internal Medicine, Joan and Sanford I. Weill Department of Medicine, and., Oromendia C; Department of Healthcare Policy and Research, Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, New York, USA., Ballman KV; Department of Healthcare Policy and Research, Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, New York, USA., Baron RM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, Massachusetts, USA., Fredenburgh LE; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, Massachusetts, USA., Higuera A; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, Massachusetts, USA., Lee JY; Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Chung CR; Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Jeon K; Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Yang JH; Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Howrylak JA; Division of Pulmonary, Allergy, and Critical Care Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA., Huh JW; Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Suh GY; Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Choi AM; Division of Pulmonary and Critical Care Medicine, Joan and Sanford I. Weill Department of Medicine.; NewYork-Presbyterian Hospital.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2018 Jul 12; Vol. 3 (13). Date of Electronic Publication: 2018 Jul 12.
DOI:	10.1172/jci.insight.99692
Abstrakt:	Background: Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. However, there is limited clinical evidence regarding the role of extracellular RIPK3 in human critical illness. Methods: Plasma RIPK3 levels were measured in 953 patients prospectively enrolled in 5 ongoing intensive care unit (ICU) cohorts in both the USA and Korea. RIPK3 concentrations among groups were compared using prospectively collected phenotypic and outcomes data. Results: In all 5 cohorts, extracellular RIPK3 levels in the plasma were higher in patients who died in the hospital compared with those who survived to discharge. In a combined analysis, increasing RIPK3 levels were associated with elevated odds of in-hospital mortality (odds ratio [OR] 1.7 for each log10-unit increase in RIPK3 level, P < 0.0001). When adjusted for baseline severity of illness, the OR for in-hospital mortality remained statistically significant (OR 1.33, P = 0.007). Higher RIPK3 levels were also associated with more severe organ failure. Conclusions: Our findings suggest that elevated levels of RIPK3 in the plasma of patients admitted to the ICU are associated with in-hospital mortality and organ failure. Funding: Supported by NIH grants P01 HL108801, R01 HL079904, R01 HL055330, R01 HL060234, K99 HL125899, and KL2TR000458-10. Supported by Samsung Medical Center grant SMX1161431.
Databáze:	MEDLINE
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