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

BACKGROUND

Currently, uniform reference values for parameters of phosphate (Pi) homeostasis-the phosphaturic hormone fibroblast growth factor 23 (FGF23) and its coreceptor, 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 Pi homeostasis, FGF23 and sKlotho.

METHODS

The HAnnover Reference values for Adults study included 504 participants (51% women) aged 18-70 years. Main outcome measures were serum 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-to-creatinine (Ca/Crea) and phosphate-to-creatinine ratios.

RESULTS

All parameters examined showed statistically significant differences between the sexes. There was a constant decrease in renal Pi reabsorption capacity (TmP/GFR, TRP) and serum Pi concentrations in older men, beginning around their sixth decade of life, whereas the parameters of Pi homeostasis in women hardly changed with age. Women had significantly lower iFGF23 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 Pi homeostasis enable the calculation of standardized z-scores to facilitate test result interpretation in women and men.