Fibroblast Growth Factor 23 and Klotho: Physiology and Pathophysiology of an Endocrine Network of Mineral Metabolism

Supplementary Data

• Download Supplemental Material as a PDF. Includes Supplemental Text: Phosphate Distribution and Homeostasis, Supplemental Figure 1: Relationship between the skeleton, intestine and kidney in mineral homeostasis (reproduced below), Supplemental Figure 2: Forms and distribution of phosphorus (reproduced below), and Supplemental Citations.

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  Supplemental Figure 1: Relationship between the skeleton, intestine and kidney in mineral homeostasis. The apatite Ca₁₀[PO₄]₆[OH]₂-based endoskeleton represents a large pool of calcium and phosphate in higher vertebrates. While Ca and P have distinct functions in the cellular compartment (bottom), this intracellular pool is infinitesimally small compared to the endoskeleton. The calcium and phosphate content in bone is in constant bidirectional flux with the extracellular fluid (ECF) compartment. Appropriate internal balance is delicately maintained. Ectopic deposition of calcium and phosphate leads to disease. The very active skeleton is destroyed and rebuilt constantly and asynchronously as part of bone modeling (growing child) and remodeling (adult) which mandates an obligatory rate of external exchange which is maintained by the intestine and kidneys. In addition to the control of Ca and P flux, there is regulatory cross-talk between these organs (blue arrows). Plasma calcium and phosphate concentrations can themselves function as signaling molecules but there are multiple additional hormones that link these organs in an endocrine network.

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  Supplemental Figure 2: Forms and distribution of phosphorus. Phosphorus exists in the blood in different compartments and multiple forms. Clinical assessment of phosphate status involves measurement of phosphorus in the plasma inorganic phosphate pool which is largely orthophosphate which in turn can be subdivided into free, complexed and protein bound fractions (5). Free phosphate exists in monovalent and divalent forms in equilibrium, which at normal plasma pH of 7.4 is 4:1 divalent:monovalent. When phosphate is excreted into the urine with a pH of 6.2, the distribution of divalent:monovalent phosphate changes to 1:4 resulting in carriage of more H⁺ and excretion of net acid.