Pathophysiology of Calcium, Phosphorus, and Magnesium Dysregulation in Chronic Kidney Disease

Semin Dial. 2015 Nov-Dec;28(6):564-77. doi: 10.1111/sdi.12411. Epub 2015 Aug 25.


Calcium, phosphorus, and magnesium homeostasis is altered in chronic kidney disease (CKD). Hypocalcemia, hyperphosphatemia, and hypermagnesemia are not seen until advanced CKD because adaptations develop. Increased parathyroid hormone (PTH) secretion maintains serum calcium normal by increasing calcium efflux from bone, renal calcium reabsorption, and phosphate excretion. Similarly, renal phosphate excretion in CKD is maintained by increased secretion of fibroblast growth factor 23 (FGF23) and PTH. However, the phosphaturic effect of FGF23 is reduced by downregulation of its cofactor Klotho necessary for binding FGF23 to FGF receptors. Intestinal phosphate absorption is diminished in CKD due in part to reduced levels of 1,25 dihydroxyvitamin D. Unlike calcium and phosphorus, magnesium is not regulated by a hormone, but fractional excretion of magnesium increases as CKD progresses. As 60-70% of magnesium is reabsorbed in the thick ascending limb of Henle, activation of the calcium-sensing receptor by magnesium may facilitate magnesium excretion in CKD. Modification of the TRPM6 channel in the distal tubule may also have a role. Besides abnormal bone morphology and vascular calcification, abnormalities in mineral homeostasis are associated with increased cardiovascular risk, increased mortality and progression of CKD.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism*
  • Disease Progression
  • Fibroblast Growth Factor-23
  • Glomerular Filtration Rate / physiology*
  • Humans
  • Kidney / physiopathology*
  • Magnesium / metabolism*
  • Metabolic Diseases / etiology*
  • Metabolic Diseases / metabolism
  • Phosphorus / metabolism*
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / metabolism
  • Renal Insufficiency, Chronic* / physiopathology


  • FGF23 protein, human
  • Phosphorus
  • Fibroblast Growth Factor-23
  • Magnesium
  • Calcium