scholarly journals FO013HIGH POTASSIUM INTAKE REDUCES FIBROBLAST GROWTH FACTOR 23 TO INCREASE RENAL PHOSPHATE REABSORPTION

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii6-iii7
Author(s):  
J. K Humalda ◽  
L. Gijsbers ◽  
J. M Geleijnse ◽  
I. J Riphagen ◽  
G. J Navis ◽  
...  
2011 ◽  
Vol 301 (2) ◽  
pp. F371-F377 ◽  
Author(s):  
Jyothsna Gattineni ◽  
Katherine Twombley ◽  
Regina Goetz ◽  
Moosa Mohammadi ◽  
Michel Baum

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosphatemic disorders. FGF23 causes hypophosphatemia by decreasing the expression of sodium phosphate cotransporters (NaPi-2a and NaPi-2c) and decreasing serum 1,25(OH)2Vitamin D3 levels. We previously showed that FGFR1 is the predominant receptor for the hypophosphatemic actions of FGF23 by decreasing renal NaPi-2a and 2c expression while the receptors regulating 1,25(OH)2Vitamin D3 levels remained elusive. To determine the FGFRs regulating 1,25(OH)2Vitamin D3 levels, we studied FGFR3−/−FGFR4−/− mice as these mice have shortened life span and are growth retarded similar to FGF23−/− and Klotho−/− mice. Baseline serum 1,25(OH)2Vitamin D3 levels were elevated in the FGFR3−/−FGFR4−/− mice compared with wild-type mice (102.2 ± 14.8 vs. 266.0 ± 34.0 pmol/l; P = 0.001) as were the serum levels of FGF23. Administration of recombinant FGF23 had no effect on serum 1,25(OH)2Vitamin D3 in the FGFR3−/−FGFR4−/− mice (173.4 ± 32.7 vs. 219.7 ± 56.5 pmol/l; vehicle vs. FGF23) while it reduced serum 1,25(OH)2Vitamin D3 levels in wild-type mice. Administration of FGF23 to FGFR3−/−FGFR4−/− mice resulted in a decrease in serum parathyroid hormone (PTH) levels and an increase in serum phosphorus levels mediated by increased renal phosphate reabsorption. These data indicate that FGFR3 and 4 are the receptors that regulate serum 1,25(OH)2Vitamin D3 levels in response to FGF23. In addition, when 1,25(OH)2Vitamin D3 levels are not affected by FGF23, as in FGFR3−/−FGFR4−/− mice, a reduction in PTH can override the effects of FGF23 on renal phosphate transport.


2018 ◽  
Vol 47 (5) ◽  
pp. 343-351
Author(s):  
Kenneth R. Phelps ◽  
Darius L. Mason

Background: The serum phosphorus concentration ([P]s) is the sum of EP/Ccr and TRP/Ccr, where Ccr is creatinine clearance and EP and TRP are rates of excretion and reabsorption of phosphate. In chronic kidney disease (CKD), parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) mediate reduction of TRP/Ccr, and [PTH] and [FGF23] are linear functions of EP/Ccr. If controls and patients with CKD are considered together, TRP/Ccr is a hyperbolic function of EP/Ccr. Given these observations, we hypothesized that hyperbolas would describe relationships of phosphate reabsorption to [PTH] and [FGF23]. Methods: We studied 30 patients and 28 controls with mean eGFR of 29.5 and 86.0 mL/min/1.73 m2, respectively. All analyses combined both subsets. We measured fasting [PTH] 1–84 and intact [FGF23], and determined contemporaneous EP/Ccr, TRP/Ccr, fractional excretion of phosphorus (FEP), and phosphate tubular maximum per volume of filtrate (TmP/GFR). We examined linear regressions of TRP/Ccr and TmP/GFR on 100/[PTH] and 100/[FGF23]; from linear equations we derived hyperbolic equations relating reabsorptive parameters to hormone concentrations. Results: TRP/Ccr and TmP/GFR were linear functions of 100/[PTH] and 100/[FGF23] and hyperbolic functions of [PTH] and [FGF23]. TRP/Ccr and TmP/GFR fell minimally over the ranges of EP/Ccr, [PTH], and [FGF23] seen in CKD. FEP rose with EP/Ccr despite stable phosphate reabsorption. Conclusions: Hyperbolas describe relationships of TRP/Ccr and TmP/GFR to [PTH] and [FGF23] if subjects with normal and reduced GFR are analyzed together. Although FEP rises with [PTH] and [FGF23] as GFR falls, the simultaneous increments do not signify hormonally mediated reductions in phosphate reabsorption.


Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4532
Author(s):  
Stanley M. H. Yeung ◽  
Ewout J. Hoorn ◽  
Joris I. Rotmans ◽  
Ron T. Gansevoort ◽  
Stephan J. L. Bakker ◽  
...  

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2–77.8) RU/mL in men, and 70.3 (56.5–89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. β −0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01–1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01–1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population.


2017 ◽  
Author(s):  
Elisa Holmlund-Suila ◽  
Maria Enlund-Cerullo ◽  
Saara Valkama ◽  
Helena Hauta-alus ◽  
Jenni Rosendahl ◽  
...  

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