ALTERED CALCIUM HOMEOSTASIS IN RENAL FAILURE

Altered Calcium Homeostasis In Renal Failure

Altered Calcium Homeostasis In Renal Failure

Introduction

Calcium is the most plentiful mineral in the body. Only one percent of the calcium in our bodies is stored in tissues and blood. The majority of the body's calcium is stored in bones and teeth. Calcium is a building block of bones, teeth, and soft tissues. On a cellular level, calcium regulates muscle and nerve functions. Calcium in the body manages blood vessel dilation and contraction which leads to changes in blood pressure. This is why many medications prescribed for blood pressure work by affecting calcium in the body. (Bakris , Weir , 2000, 93)

Tubular cell calcium concentration and content rise following acute renal injury induced by ischemic and toxic insults. Since calcium plays a critical role in many cell functions and the proximal tubule appears to be a major site of injury in acute renal failure, it is possible that cell calcium overload plays a direct role in the pathogenesis of acute renal failure. (Bash , Erlinger , Coresh , 2009, 596)Tubular cell calcium overload has been associated with altered function at the level of the plasma membrane, mitochondria, endoplasmic reticulum and cytoskeleton. While there is evidence to support a role for calcium in acute renal injury, the importance of cell calcium overload needs to be further explored. Furthermore, alterations in extracellular calcium and mineral metabolism may be involved in some aspects of acute renal failure and recovery. Calcium channel blockers and other interventions designed to modulate calcium changes may have a role in the treatment of acute renal failure(Choi , et al, 2009, 8).

Physiology

The extracellular calcium-sensing receptor (CaSR) plays a major role in the maintenance of a physiological serum ionized Ca2+ (Ca2+) concentration by regulating the circulating levels of parathyroid hormone. It was molecularly identified in 1993 by Brown et al. in the laboratory of Dr. Steven Hebert using an expression cloning strategy. Subsequent studies have demonstrated that the CaSR is highly expressed in the kidney, where it is capable of integrating signals deriving from the tubular fluid and/or the interstitial plasma. Additional studies elucidating inherited and acquired mutations in the CaSR gene, the existence of activating and inactivating autoantibodies and genetic polymorphisms of the CaSR have greatly enhanced our understanding of the role of the CaSR in mineral ion metabolism. (Bligh , 2000, 143)Allosteric modulators of the CaSR are the first drugs on their class to become available for clinical use and have been shown to treat successfully hyperparathyroidism secondary to advanced renal failure. In addition, pre-clinical and clinical studies suggest the possibility of using such compounds in various forms of hypercalcemic hyperparathyroidism, such as primary and lithium-induced hyperparathyroidism and that occurring post-renal transplantation. This review addresses the role of the CaSR in kidney physiology and pathophysiology as well as current and in-the-pipeline treatments utilizing CaSR-based therapeutics.

What is Calcium and what does it do?

Calcium is absorbed from the foods we eat in the small intestine where it is then transported in ...