Renal Clearance of Fibroblast Growth Factor-23 (FGF23) and its Fragments in Humans

Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 and C-terminal fragments) versus intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this finding. We measured cFGF23 and iFGF23 in the aorta and bilateral renal veins of 162 patients with essential hypertension undergoing renal angiography. Using multivariable linear regression, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar parameters and with addition of urine concentrations of cFGF23 and iFGF23 were measured in six Wistar rats. Mean ± standard deviation (SD) age was 54 ± 12 years, 54% were women, and mean creatinine clearance was 72 ± 48 mL/min/100 g. The human kidney reduced the concentrations of both cFGF23 (16% ± 12%) and iFGF23 (21% ± 16%), but reduction was higher for iFGF23. Greater kidney creatinine and PTH reductions were each independently associated with greater reductions of both cFGF23 and iFGF23. The greater kidney reduction of iFGF23 compared to cFGF23 appeared stable and consistent across the range of creatinine clearance evaluated. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23. Renal reduction of iFGF23 is higher than that of creatinine and cFGF23. Our data suggest that FGF23 is metabolized by the kidney. However, the major cell types involved in metabolization of FGF23 requires future study. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function. © 2022 American Society for Bone and Mineral Research (ASBMR).