Calcium Homeostasis in Health and in Kidney Disease

Calcium is an important ion in cell signaling, hormone regulation, and bone health. Its regulation is complex and intimately connected to that of phosphate homeostasis. Both ions are maintained at appropriate levels to maintain the extracellular to intracellular gradients, allow for mineralization of bone, and to prevent extra skeletal and urinary calcification. The homeostasis involves the target organs intestine, parathyroid glands, kidney, and bone. Multiple hormones converge to regulate the extracellular calcium level: parathyroid hormone, vitamin D (principally 25(OH)D or 1,25(OH)2D), fibroblast growth factor 23, and α-klotho. Fine regulation of calcium homeostasis occurs in the thick ascending limb and collecting tubule segments via actions of the calcium sensing receptor and several channels/transporters. The kidney participates in homeostatic loops with bone, intestine, and parathyroid glands. Initially in the course of progressive kidney disease, the homeostatic response maintains serum levels of calcium and phosphorus in the desired range, and maintains neutral balance. However, once the kidneys are no longer able to appropriately respond to hormones and excrete calcium and phosphate, positive balance ensues leading to adverse cardiac and skeletal abnormalities. © 2016 American Physiological Society. Compr Physiol 6:1781-1800, 2016.