Baseline Proenkephalin A (PENK) predicts worse kidney outcomes and higher mortality with hydrocortisone in septic shock.

Septic shock is a life-threatening condition characterized by severe infection leading to organ dysfunction and dangerously low blood pressure. Corticosteroids like hydrocortisone are often used, but their benefits are inconsistent, possibly due to patient heterogeneity. The kidneys play a crucial role in sepsis pathophysiology and corticosteroid metabolism. Proenkephalin A (PENK) is a promising biomarker for renal function, and understanding its interaction with hydrocortisone could help personalize treatment.

This was a post hoc analysis of the double-blind, randomized VANISH trial, involving 173 septic shock patients in UK ICUs. Patients were randomized to norepinephrine vs. vasopressin and hydrocortisone vs. placebo. Plasma PENK levels were measured at baseline and patients were dichotomized into high (≥ 89 pmol/L) or low PENK groups. The primary endpoint for this analysis was kidney failure-free days, with 28-day mortality as a secondary outcome, specifically examining interactions with hydrocortisone treatment.