Age- and sex-specific serum creatinine reference curves in children and adolescents with Down syndrome

To derive age- and sex-specific serum creatinine centile curves for children and adolescents with Down syndrome (DS) and compare them with DS-specific references. This retrospective reference-interval study included cytogenetically confirmed, post-neonatal individuals with DS followed at a tertiary center in Türkiye from 2015 to 2025. Individuals with kidney/urinary disease or other conditions expected to affect creatinine distribution were excluded. Kinetic Jaffe creatinine measurements were modeled separately by sex using Generalized Additive Models for Location, Scale, and Shape (GAMLSS), with subject-level bootstrap confidence intervals. Derived centiles were compared descriptively with published DS-specific references. The analytic cohort included 523 children and adolescents contributing 2172 creatinine measurements. Serum creatinine increased nonlinearly with age in both sexes, with progressive sex separation during adolescence. The 97.5th centile increased from 0.44 mg/dL (39 μmol/L) in early infancy to 1.32 mg/dL (117 μmol/L) at 17 to 18 years in boys, and from 0.42 mg/dL (37 μmol/L) to 1.01 mg/dL (89 μmol/L) in girls. Compared with previous DS-specific cohorts, the curves were closely aligned with French GAMLSS-derived centiles during childhood, while upper-centile values were higher than Japanese age-banded references, most notably in adolescent boys (maximum difference, 0.21 mg/dL at 16 to < 17 years).

These DS-specific centiles support age- and sex-adapted interpretation of serum creatinine. Differences from previous DS-specific references suggest that creatinine centiles may vary by cohort, anthropometry, assay method, and modeling approach.

• Children with Down syndrome have distinct growth and body-composition patterns and increased kidney and urinary tract morbidity, supporting syndrome-specific interpretation of serum creatinine. • Down syndrome-specific pediatric creatinine data remain limited to a few cohorts.

• This study provides age- and sex-specific serum creatinine centile curves from the post-neonatal period to < 18 years. • The curves show nonlinear age-related changes, increasing sex separation during adolescence, and between-cohort variation compared with previous references.