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• W3204274021 abstract "Background: Relative abundance of fibroblast growth factor-23 (FGF23) measured by the C-terminal (cFGF23, which measures both intact FGF23 & c-terminal fragments) vs intact (iFGF23, measures only intact hormone) assays varies by kidney function in humans. Differential kidney clearance may explain this.Methods: 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 models, we examined factors associated with aorta to renal vein reduction of FGF23 using both assays. Similar, parameters and urine concentrations were measured in 6 Wistar rats.Results: Mean age was 54±12 years, 54% percent were women, and mean creatinine clearance was 72±48 ml/min/100g. The human kidney reduces the concentrations of both cFGF23 (16±12%) and iFGF23 (21±16%) compared to aorta, but reduction was higher for iFGF23. Greater kidney creatinine and PTH reduction were each independently associated with greater reductions of both cFGF23 and iFGF23. The relative kidney reduction of iFGF23 and cFGF23 appeared stable and consistent across the range of creatinine clearance. Kidney clearance was similar, and urine concentrations of both assays were low in the rat models, suggesting kidney metabolism of both cFGF23 and iFGF23.Conclusions: Renal reduction of iFGF23 is higher than that of creatinine and cFGF23.FGF23 is likely metabolized and cleared through the human kidney tubules, above and beyond glomerular filtration. Kidney clearance of FGF23 does not explain differences in C-terminal and intact moieties across the range of kidney function.Funding: This work was supported by National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) Grants R01DK119528 and K24DK110427 (J.H.I). P30 DK079328, R01 DK091392, R01 DK092461 and R01 DK119528 (O.W.M). Veterans Health Administration IK2-CX002195 (SS).Declaration of Interest: Dr. Ix is principal investigator of an investigator-initiated research grant from Baxter International, serves as a data safety monitoring board member for Sanifit International, and has served on advisory boards for Alpha Young, AstraZeneca, Ardelyx Inc., and Jnana Inc. Dr. Moe has served on advisory boards and received compensations in the last 5 years for Allena, Alnylam, Ardelyx, Applied Therapeutics, Dicerna, Janssen, Genzyme-Sanofi, and Tricida. Remaining authors have declared no conflicts of interest.Ethical Approval: The human renal angiography studies were approved by the medical ethical committee of the Maastricht University Hospital. Animal studies were performed in accordance with the National Institutes for Health’s Guide for Care and Use of Laboratory Animals, and the experimental protocols had gained approval by the VA San Diego Health Care Systems and conducted under their guidelines." @default.
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• W3204274021 date "2021-01-01" @default.
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• W3204274021 title "Renal Clearance of FGF23 and its Fragments in Humans" @default.
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• W3204274021 doi "https://doi.org/10.2139/ssrn.3927774" @default.
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