Reference values for serum proenkephalin in a pediatric and young adult cohort

The novel biomarker Proenkephalin A 119-159 (PENK) has emerged as a promising marker of kidney function, with the potential to perform comparably to invasive gold-standard methods. This study provides the first reference values for PENK in a German pediatric and young adult cohort, with a particular focus on age-specific values.

PENK was measured in serum using a double-monoclonal sandwich immunoassay in a cohort of individuals aged 1 month-40 years. The study included 221 participants, comprising 188 pediatric participants (< 18 years) and 33 adults (≥ 18 years). The upper reference limit was defined as the estimated 97.5th percentile derived using quantile regression with lambda-mu-sigma (LMS).

Serum PENK concentrations declined with age during the first 20 years of life. In the combined-sex cohort, the estimated 97.5th percentile decreased from 618 pmol/L in the first month of life to 103 pmol/L at age 20 years. Thereafter, the 97.5th percentile remained stable in young adults (>20 years), ranging from 86 to 93 pmol/L. Similarly, the estimated 50th percentile declined from 346 pmol/L in the first month of life to 58 pmol/L at age 20 years, remaining stable thereafter at 48-52 pmol/L. No statistically significant differences in PENK concentrations were observed between females and males within the respective age groups.

This study provides the first age-dependent reference values for PENK. These reference values are a prerequisite for future studies evaluating the precision and clinical utility of PENK as a diagnostic biomarker across all age groups, particularly in pediatric populations.