Oral Phosphate Supplementation Corrects Hypophosphatemia and Normalizes Plasma FGF23 and 25-Hydroxyvitamin D₃ Levels in Women with Chronic Metabolic Acidosis

Abstract

Background: Chronic metabolic acidosis (CMA) is known to induce renal phosphate wasting and hypophosphatemia by enhancing bone resorption and inhibiting renal phosphate reabsorption. However, nothing is known regarding changes in the plasma levels of phosphate-regulating hormones during CMA, especially in humans with normal kidney function.

Methods: Fifteen healthy Thai female volunteers were given NH₄Cl orally for 7 days to induce CMA with or without oral phosphate supplementation. Blood and 24-h urine specimens were collected prior to and after CMA induction. Plasma concentrations and fractional excretion of calcium and inorganic phosphate as well as plasma levels of fibroblast growth factor (FGF) 23, 25(OH)D₃, 1,25(OH)₂D₃ and intact parathyroid hormone (iPTH) were determined.

Results: CMA led to hypophosphatemia and hypocalcemia with increases in the fractional excretion of calcium and phosphate. Plasma concentrations of FGF23, 25(OH)D₃ and iPTH were decreased, whereas that of 1,25(OH)₂D₃ was increased. After oral phosphate supplementation, CMA-induced changes in the concentrations of the studied ions, FGF23 and 25(OH)D₃, but not those of 1,25(OH)₂D₃ and iPTH, were diminished.

Conclusions: The CMA-induced hypophosphatemia was likely to initiate a negative feedback response, thereby leading to reduction in the plasma levels of hyperphosphaturic hormones, FGF23 and PTH. An increase in the plasma 1,25(OH)₂D₃ level, despite diminishing 25(OH)D₃ storage pool, may help enhance the intestinal phosphate absorption. Oral phosphate supplementation abolished the effects of CMA on FGF23 and 25(OH)D₃ levels, suggesting that the plasma phosphate concentration is the primary regulator of the plasma levels of these hormones during CMA.

Key words

acidemia - ammonium chloride - fibroblast growth factor 23 (FGF23) - parathyroid hormone

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