Proenkephalin for Cardiovascular and All-Cause Mortality: The REasons for Geographic and Racial Differences in Stroke...

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Biomarker Research

Background:

• Kidney dysfunction increases mortality risk, particularly cardiovascular mortality.
• Current markers like eGFR and UACR may not fully capture this risk.
• Proenkephalin (PENK) is an emerging biomarker for kidney glomerular function.

Purpose of the Study:

• To evaluate the association of PENK with all-cause and cardiovascular mortality.
• To determine if PENK associations vary by sex and race.
• To assess PENK's added value beyond eGFR and UACR.

Main Methods:

• Analysis of 1,021 Black and White participants from the REGARDS cohort.
• Use of multivariable Cox-proportional hazard models.
• Adjustment for confounders including UACR and eGFR (2021 CKD-EPI equation).
• Testing for effect modification by sex and race.

Main Results:

• PENK was associated with higher all-cause mortality risk after adjusting for UACR, but not after adjusting for eGFR.
• PENK was associated with cardiovascular mortality after adjusting for UACR, but not after adjusting for eGFR.
• A significant interaction by sex was observed, with higher PENK associated with lower mortality in women.
• No significant interaction by race was found.

Conclusions:

• PENK does not provide additional risk stratification for mortality beyond current measures like eGFR.
• Current kidney function biomarkers appear sufficient for risk assessment in this context.