Table 2.

Causes of Hyperphosphatemia

Increased Extracellular Phosphate Load	Examples	Pathogenesis	Targeted Interventions
Acquired
High phosphate intake	Acute Pi intake, phosphate-containing laxatives	Decreased GFR or large acute intakes of phosphate can overwhelm renal Pi excretion capacity
Tissue or cell injury	Tumor lysis syndrome, rhabdomyolysis, ketoacidosis, lactic acidosis	Pi is the major intracellular anion. Acute cellular release of Pi due to cellular injury or acid-base disturbances can result in extracellular Pi increase	Intravenous fluids to increase GFR
Increased intestinal absorption of phosphate
Acquired 1–25(OH)2 Vit D excess	High intake of vitamin D supplements	Vitamin D increases Pi absorption and decreases PTH secretion, thereby also limiting Pi excretion
Decreased urinary excretion
Genetic Familial tumoral calcinosis	Mutations in FGF-23, GALNT3 or Klotho genes	Mutations in GALNT3 result in lower levels of biologically active FGF-23 by increased cleavage. Mutations in FGF-23 or its co-receptor klotho, directly impair FGF-23 mediated Pi excretion
PTH insufficiency	PTH mutations, GNAS mutations, PTH1R mutations	PTH mutations result in hypoparathyroidism, while downstream mutations such as the PTH1R or Gsα result in PTH resistance (PHP)
Acquired
PTH insufficiency	Surgical or autoimmune hypoparathyroidism	Increased reabsorption of Pi due to impaired PTH mediated Pi excretion. Associated with hypocalcemia	PTH analogs in hypoparathyroidism
Lower GFR	AKI, CKD	Occurs mainly at GFR falls below 20 to 25 mL/min	Phosphate binders, dialysis
Medications	FGFR inhibitors, etidronate	Increased reabsorption of Pi due to pharmacological blockage of FGF-23 actions

Abbreviations: FGF-23, fibroblast growth factor-23; GALNT3, uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylga-lactosaminyltransferase 3; Gsα, alpha subunit of stimulatory G protein; PHP, pseudohypoparathyroidism; PTH, parathyroid hormone; PTH1R, parathyroid hormone/parathyroid hormone-related peptide receptor type 1.