LMS-Based Pediatric Reference Values for Parameters of Phosphate Homeostasis in the HARP Cohort

Abstract

Abstract Context The assessment of phosphate homeostasis in children is challenging due to the marked changes in laboratory parameters during growth and development, and the lack of adequate reference values. Objective To develop Lambda-Mu-Sigma (LMS)-based continuous pediatric reference percentiles for 7 key laboratory parameters of phosphate homeostasis. Methods This cross-sectional, single-center study, the HAnnover Reference values for Pediatrics (HARP) study, included 455 children aged 0.1-18 years (254 boys) from outpatient hospital clinics and a secondary school program. Main outcome measures were LMS-based continuous reference percentiles for serum phosphate, plasma intact fibroblast growth factor 23 (iFGF23), and its cofactor soluble Klotho (sKlotho), tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR), fractional tubular reabsorption of phosphate (TRP), and urinary calcium/creatinine (Ca/Crea) and phosphate/creatinine (Pi/Crea) ratios. Results LMS-based percentiles and z-scores were established for 7 key laboratory parameters of phosphate homeostasis, which were all found to be age-dependent. Serum phosphate, TmP/GFR, and sKlotho associated with sex. Serum phosphate, TmP/GFR, and urinary Ca/Crea and Pi/Crea levels were highest in infancy and declined until age 18 years, while phosphate and TmP/GFR values reached adult levels earlier in girls compared to boys. iFGF23 concentrations are highest in infancy and fall to a stable plateau by 4 years of age, while sKlotho peaks during adolescence. Conclusion This is the first report of LMS-based continuous pediatric reference percentiles for key laboratory parameters of phosphate homeostasis that allow calculation of standardized patient z-scores to facilitate test result interpretation in children and adolescents.