Calcium and phosphate homeostasis: Concerted interplay of new regulators

Figures & data

Figure 1 Transcellular Ca²⁺ and P_i transport. Active Ca²⁺ and P_i transport across renal and intestinal epithelium. A: Ca²⁺ influx is mediated by TRPV5 in the renal distal convoluted and connecting tubules and TRPV6 in the duodenum. Subsequently, Ca²⁺ is transported across the cell to the basolateral membrane by Ca²⁺‐binding proteins calbindin‐D_28K (kidney) and calbindin‐D_9K (intestine). Extrusion into the blood takes place via the plasma membrane Ca²⁺‐ATPase (PMCA1b) in the intestine and sodium‐Ca²⁺ exchanger (NCX1) and PMCA1b in the kidney. B: The ileal brush border, sodium‐dependent P_i cotransporter, NaPi‐IIb, mediates entry of P_i into enterocytes. In the proximal tubules, NaPi‐IIa and NaPi‐IIc are responsible for P_i entry into the tubular epithelial cells. The transport mechanisms involved in basolateral extrusion of P_i into blood are unknown both in the intestine and kidney.

Figure 2 Key players in Ca²⁺ and P_i homeostasis. The concerted interplay of intestinal uptake, reabsorption in kidney, and bone (de)mineralization establishes the maintenance of a normal Ca²⁺ and P_i balance. The calcium sensing receptor (CaSR), present in the thyroid gland, senses blood Ca²⁺ levels and triggers the secretion of the calcitropic hormones parathyroid hormone (PTH) and calcitonin. Ovarian‐produced estrogen stimulates Ca²⁺ reabsorption also. Similar hormones are involved in the regulation of P_i balance. Blood P_i levels are controlled by PTH, 1,25(OH)₂D₃, klotho, and fibroblast growth factor member 23 (FGF23). A negative feedback mechanism prevents the accumulation of FGF23 and klotho since 1αOHase‐mediated 1,25(OH)₂D₃ production is inhibited by FGF23 and klotho.