title: Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema.
abstract: Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia. We report the case of an 83-year-old woman with hyperphosphatemia and hypocalcemia resulting from phosphate-containing enemas. PTH and calcitriol increased in response to hypocalcemia, and FGF23 increased in response to hyperphosphatemia. Unexpectedly, peak FGF23 did not coincide with peak serum phosphate. Rather, peak FG23 was observed only after severe hypocalcemia was partially corrected with exogenous calcium administration, even though serum phosphate had been already decreasing for 32 h. Correction of severe hypocalcemia was thus associated with peak FGF23 values and with a precipitous decrease in PTH. Peak FGF23 was followed by an accelerated decrease in serum phosphate and significant phosphaturia. This clinical report is consistent with experimental data in rats showing a blunted FGF23 response to high phosphate in the presence of severe hypocalcemia. Thus, complementary experimental and clinical data suggest that partial correction of severe hypocalcemia is required for optimal FGF23-mediated phosphaturia, which takes place despite correction of PTH levels. We believe this the first human report suggesting blunting of the FGF23 response to high phosphate by severe hypocalcemia.
authors.affiliation: IIS-Fundación Jiménez Díaz, Unidad de Diálisis, Avd. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gracia-Iguacel
authors.forename: Emilio
authors.initials: E
authors.lastname: Gonzalez-Parra
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez-Osorio
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Sanz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Almaden
authors.forename: Concepcion
authors.initials: C
authors.lastname: de la Piedra
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Mariano
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000369:Aged, 80 and over; D002117:Calcitriol / Q000097:blood / Q000378:metabolism; D004733:Enema / Q000379:methods; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000378:metabolism*; D006996:Hypocalcemia / Q000097:blood / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol