Elsevier

Kidney International

Volume 74, Issue 3, 1 August 2008, Pages 276-288
Kidney International

Translational Nephrology
Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics

https://doi.org/10.1038/sj.ki.5002287Get rights and content
Under an Elsevier user license
open archive

The identification of the calcium-sensing receptor (CaSR) and the clarification of its role as the major regulator of parathyroid gland function have important implications for understanding the pathogenesis and evolution of secondary hyperthyroidism in chronic kidney disease (CKD). Signaling through the CaSR has direct effects on three discrete components of parathyroid gland function, which include parathyroid hormone (PTH) secretion, PTH synthesis, and parathyroid gland hyperplasia. Disturbances in calcium and vitamin D metabolism that arise owing to CKD diminish the level of activation of the CaSR, leading to increases in PTH secretion, PTH synthesis, and parathyroid gland hyperplasia. Each represents a physiological adaptive response by the parathyroid glands to maintain plasma calcium homeostasis. Studies of genetically modified mice indicate that signal transduction via the CaSR is a key determinant of parathyroid cell proliferation and parathyroid gland hyperplasia. Because enlargement of the parathyroid glands has important implications for disease progression and disease severity, it is possible that clinical management strategies that maintain adequate calcium-dependent signaling through the CaSR will ultimately prove useful in diminishing parathyroid gland hyperplasia and in modifying disease progression.

Keywords

parathyroid hyperplasia
secondary hyperparathyroidism
calcium-sensing receptor
vitamin D receptor
chronic kidney disease
parathyroid hormone

Cited by (0)