Age and sex-specific reference values for phosphate homeostasis parameters, fibroblast growth factor 23 and soluble Klotho

Abstract Background Currently, uniform reference values for parameters of phosphate homeostasis, the phosphaturic hormone fibroblast growth factor 23 (FGF23) and its co-receptor, soluble klotho (sKlotho), are used for women and men regardless of age. This may not be adequate, especially in older subjects. We established Lambda-Mu-Sigma (LMS)-based continuous age and sex-specific reference values for key parameters of phosphate homeostasis, FGF23 and sKlotho. Methods The HAnnover Reference values for Adults (HARA) study included 504 participants (51% women) aged 18–70 years. Main outcome measures were serum phosphate (Pi), intact (iFGF23) and total FGF23, 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 All parameters examined showed statistically significant differences between the sexes. There was a constant decrease in renal phosphate reabsorption capacity (TmP/GFR, TRP) and serum phosphate concentrations in older men, beginning around their sixth decade of life, whereas the parameters of phosphate homeostasis in women hardly changed with age. Women had significantly lower intact but slightly higher total FGF23 concentrations. sKlotho concentrations decreased with age in both sexes, with women generally having higher concentrations than men regardless of the age related decline in kidney function. Women taking estrogen-containing oral contraceptives had lower sKlotho concentrations than their peers. Women showed higher urine Ca/Crea values than men. Conclusion The presented LMS-based continuous reference values for key parameters of phosphate homeostasis enable the calculation of standardized z-scores to facilitate test result interpretation in women and men.