Admission Serum Receptor-Interacting Protein Kinase-1 as a Biomarker of Severity and a Prognostic Factor in Aneurysmal Subarachnoid Hemorrhage.

Objective: Receptor-interacting protein kinase-1 (RIPK1), a regulator of necrotic apoptosis, is involved in acute brain injury. This study was designed to investigate whether serum RIPK1 levels are related to severity and poor clinical outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this multicenter prospective cohort study of 224 patients with aSAH and 100 controls, severity appraisal was completed by applying the Hunt-Hess and modified Fisher (mFisher) gradings, and neurological function was evaluated by using the modified Rankin Scale (mRS) at post-aSAH three months. A single blood-drawing was performed at admission of patients, and the enzyme-linked immunosorbent assay was used to measure serum RIPK1 levels. Multivariate analyses were adopted to determine relation of serum RIPK1 levels with severity, delayed cerebral ischemia (DCI) and 3-month poor prognosis following aSAH (mRS 3-6). Results: Median interval time between symptom ictus and blood drawings was 6.9 h (lower-upper quartiles, 4.8-11.3 h). Serum RIPK1 levels were significantly elevated in aSAH patients compared to controls and were independently associated with Hunt-Hess and mFisher scores. Higher RIPK1 levels correlated with increased risk of DCI and poor 3-month outcomes. The two respective combined predictive models incorporating RIPK1, Hunt-Hess, and mFisher scores demonstrated superior prognostic accuracy compared to each variable alone. Conclusion: Elevated serum RIPK1 levels after aSAH are closely associated with disease severity, and can effectively predict the occurrence of DCI and poor prognosis at 3 months post-aSAH. Thus, serum RIPK1 may be a potential prognostic biomarker of aSAH.