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

ABSTRACT: 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.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.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.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.Supported by NIH grants P01 HL108801, R01 HL079904, R01 HL055330, R01 HL060234, K99 HL125899, and KL2TR000458-10. Supported by Samsung Medical Center grant SMX1161431.

SUBMITTER: Ma KC

PROVIDER: S-EPMC6124535 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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

Ma Kevin C KC Schenck Edward J EJ Siempos Ilias I II Cloonan Suzanne M SM Finkelsztein Eli J EJ Pabon Maria A MA Oromendia Clara C Ballman Karla V KV Baron Rebecca M RM Fredenburgh Laura E LE Higuera Angelica A Lee Jin Young JY Chung Chi Ryang CR Jeon Kyeongman K Yang Jeong Hoon JH Howrylak Judie A JA Huh Jin-Won JW Suh Gee Young GY Choi Augustine Mk AM

JCI insight 20180712 13

<h4>Background</h4>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.<h4>Methods</h4>Plasma RIPK3 levels were measured in 953 ...[more]

PMID: 29997296

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Dataset Information

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

Publications

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

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