High proenkephalin and hydrocortisone were linked to fewer kidney-failure-free days in septic shock

Design

Post hoc biomarker analysis of a double-blind factorial randomised trial

Population

173 adults with septic shock in UK ICUs (VANISH)

Primary outcome

Kidney-failure-free days and 28-day mortality by proenkephalin and treatment

Effect

High PENK: 11 (hydrocortisone) vs 26 (placebo) kidney-failure-free days; interaction p = 0.01

This post hoc analysis of the VANISH trial measured proenkephalin A, a marker of glomerular filtration, in 173 patients with septic shock randomised to vasopressin or noradrenaline and to hydrocortisone or placebo. Patients were split at 89 pmol/L.

High proenkephalin was associated with 28-day mortality (OR 3.24, 1.62–6.74). Among the 111 patients reaching maximum vasopressor dose, proenkephalin modified the effect of hydrocortisone on kidney-failure-free days: with high proenkephalin, median days were 11 with hydrocortisone and 26 with placebo; with low proenkephalin, 28 in both (interaction p = 0.01). The mortality interaction was not significant.

The kidney is central to both septic shock and corticosteroid handling, so the hypothesis is reasonable, but this is a small, exploratory subgroup finding. It is a reason for prospective testing, not for withholding steroids in patients with poor kidney function.

• Do not withhold hydrocortisone in septic shock on the basis of kidney function from this analysis.
• Proenkephalin is a research marker of filtration, not a routine test.
• The signal came from 111 patients in a post hoc subgroup and needs prospective confirmation.
• Track kidney outcomes when using corticosteroids in septic shock with established AKI.

Why it matters

It raises the possibility that baseline kidney function changes how steroids act in septic shock.

Don't overread it

This exploratory post hoc finding does not show that hydrocortisone harms kidneys in septic shock.

The statistics, in plain English

A significant interaction in one of several post hoc analyses can easily arise by chance, especially with 111 patients. The very wide ranges around median kidney-failure-free days add to that uncertainty.

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