The roles of calcium-sensing receptor (CaSR) in heavy metals-induced nephrotoxicity

Anthony A. Kosiba, Yanwei Wang, Dongfeng Chen, Chris K C Wong, Jie Gu*, Haifeng Shi*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

14 Citations (Scopus)


The kidney is a vital organ responsible for regulating water, electrolyte and acid-base balance as well as eliminating toxic substances from the blood in the body. Exposure of humans to heavy metals in their natural and occupational environments, foods, water, and drugs has serious implications on the kidney's health. The accumulation of heavy metals in the kidney has been linked to acute or chronic renal injury, kidney stones or even renal cancer, at the expense of expensive treatment options. Therefore, unearthing novel biomarkers and potential therapeutic agents or targets against kidney injury for efficient treatment are imperative. The calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR) is typically expressed in the parathyroid glands and renal tubules. It modulates parathyroid hormone secretion according to the serum calcium (Ca2+) concentration. In the kidney, it modulates electrolyte and water excretion by regulating the function of diverse tubular segments. Notably, CaSR lowers passive and active Ca2+ reabsorption in distal tubules, which facilitates phosphate reabsorption in proximal tubules and stimulates proton and water excretion in collecting ducts. Moreover, at the cellular level, modulation of the CaSR regulates cytosolic Ca2+ levels, reactive oxygen species (ROS) generation and the mitogen-activated protein kinase (MAPK) signaling cascades as well as autophagy and the suppression of apoptosis, an effect predominantly triggered by heavy metals. In this regard, we present a review on the CaSR at the cellular level and its potential as a therapeutic target for the development of new and efficient drugs against heavy metals-induced nephrotoxicity.

Original languageEnglish
Article number117183
JournalLife Sciences
Publication statusPublished - 1 Feb 2020

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

User-Defined Keywords

  • Apoptosis
  • Autophagy
  • Calcium-sensing receptor
  • Heavy metals
  • Intracellular Ca signaling
  • Nephrotoxicity


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