Endoplasmic Reticulum Calcium Homeostasis in Kidney Disease: Pathogenesis and Therapeutic Targets.

Calcium (Ca) homeostasis is a crucial determinant of cellular function and survival. Endoplasmic reticulum (ER) acts as the largest intracellular Ca store that maintains Ca homeostasis through the ER Ca uptake pump, sarco/ER-Ca ATPase, ER Ca release channels, inositol 1,4,5-trisphosphate receptor channel, ryanodine receptor, and Ca-binding proteins inside of the ER lumen. Alterations in ER homeostasis trigger ER Ca depletion and ER stress, which have been associated with the development of a variety of diseases. In addition, recent studies have highlighted the role of ER Ca imbalance caused by dysfunction of sarco/ERCa ATPase, ryanodine receptor, and inositol 1,4,5-trisphosphate receptor channel in various kidney diseases. Despite progress in the understanding of the importance of these ER Ca channels, pumps, and binding proteins in the pathogenesis of kidney disease, treatment is still lacking. This mini-review is focused on: i) Ca homeostasis in the ER, ii) ER Ca dyshomeostasis and apoptosis, and iii) altered ER Ca homeostasis in kidney disease, including podocytopathy, diabetic nephropathy, albuminuria, autosomal dominant polycystic kidney disease, and ischemia/reperfusion-induced acute kidney injury.