The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Renkema, Kirsten Y.; Velić, Ana; Dijkman, Henry; Verkaart, Sjoerd; Kemp, Annemiete W. van der; Nowik, Marta; Timmermans, Kim; Doucet, Alain; Wagner, Carsten A.; Bindels, René J. M.; Hoenderop, Joost G. J.

doi:10.1681/asn.2008111195

Cited by 122 publications

(100 citation statements)

References 53 publications

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“…These findings suggested that an increased luminal Ca 2ϩ concentration, as consistently present in the renal DCT, CNT, and CD of Trpv5 knockout mice, stimulates H ϩ -ATPase activity via apical CaSR activation. Interestingly, additional gene ablation of Atp6v1b1 in Trpv5 knockout mice resulted in normalization of urinary pH levels and led to the tubular precipitation of Ca 2ϩ -phosphate in the medullary CD ( Figure 1) (32). From previous studies it was known that the formation of alkaline urine increases the risk for Ca 2ϩ -phosphate precipitation (33).…”

Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 94%

“…Further investigations provided insight into the underlying molecular mechanisms applicable in kidney stone prevention (32). The crystallization of Ca 2ϩ -phosphate occurs via the conversion of phosphate to its divalent form (HPO 4 2Ϫ ) in an alkaline, rather than in an acidic, environment.…”

Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 99%

“…The vacuolar proton pump H ϩ -ATPase, located in the type A intercalated cells of the CD, is mainly responsible for urinary H ϩ excretion. In 2009, we described how the exposure to high (5.0 mM) Ca 2ϩ concentrations significantly enhanced H ϩ -ATPase activity in CD cells (32). This stimulatory effect was absent in CD cells from Atp6v1b1 knockout mice that were genetically ablated for the CD-specific B1 subunit of H ϩ -ATPase (35).…”

Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 99%

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Role of the Calcium-Sensing Receptor in Reducing the Risk for Calcium Stones

Renkema

Bindels²,

Hoenderop³

2011

Clinical Journal of the American Society of Nephrology

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SummaryThe tight control of blood Ca 2؉ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca 2؉ . It is the concerted action of intestine, bone, and kidney that controls the Ca 2؉ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca 2؉ , respectively. Along the nephron, fine-tuning of blood Ca 2؉ levels takes place by Ca 2؉ reabsorption. The calciotropic hormones regulate Ca 2؉ transport processes, leading to whole-body Ca 2؉ homeostasis and, importantly, preserving a constant Ca 2؉ concentration in the blood. Defects in renal Ca 2؉ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca 2؉ management and describe the in-depth investigations on a renal hypercalciuric model of disease, the Trpv5 knockout mouse, which naturally displays molecular adaptations that prevent Ca 2؉ precipitation in the kidney.

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Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 94%

Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 99%

Section: Casr Activation Decreases the Risk To Renal Stone Formation mentioning

confidence: 99%

See 1 more Smart Citation

Role of the Calcium-Sensing Receptor in Reducing the Risk for Calcium Stones

Renkema

Bindels²,

Hoenderop³

2011

Clinical Journal of the American Society of Nephrology

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“…Experiments in hypercalciuric knockout mice for the TRPV5 calcium channel showed that CaSR stimulated proton-secreting H-pump in the type A intercalated cells and free water excretion by inhibition of aquaporin (AQP2) membrane expression in principal cells. 34,35 The genetic background of stone formation…”

Section: Casr In Collecting Ductsmentioning

confidence: 99%

Calcium-sensing receptor gene polymorphisms in patients with calcium urolithiasis: a systematic review

et al. 2014

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Background: Calcium-sensing receptor gene (CaSR) might be a strong component of the complex genetic background regulating calcium excretion and stone formation in kidney. The polymorphisms in different parts of the gene could be associated with calcium stone formation. Objective: The individual studies indicate a correlation between CaSR gene polymorphisms and urolithiasis but not sufficient to draw a precise result. We aimed to search literature to come to a reliable conclusion through a systematic review. Materials and methods: We have serached individiual studies regarding the issue and high quality reviews. We assessed all the studies to draw a conclusion. Conclusion: The genetic background of the neprolithiasis is an interesting issue deserving to be disscussed on. Regading genes of which, CaSR gene polymorphisms is the leading one, are studied in many individual studies but they are not sufficient to have a precise conclusion. Well-oriented and documented, phenotypically homogenous large cohort studies are needed for further evaluation.

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“…These latter effects have been proposed as a mechanism that normally protects the kidney from calcification induced by hypercalciuria but would tend to foster volume depletion and metabolic alkalosis. 28,30 This latter hypothesis regarding hypercalciuria is controversial. 31 The main therapy for the calcium-alkali syndrome is volume expansion with saline to break the self-propagating reclamation cycle induced by exposure to calcium alkali.…”

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confidence: 99%