TRPV5-mediated Ca²⁺ reabsorption and hypercalciuria

The concerted action of the intestine, kidney and bone results in the maintenance of a normal Ca²⁺ balance, a mechanism that is tightly controlled by the calciotropic hormones vitamin D, parathyroid hormone and calcitonin. Disturbances in the Ca²⁺ balance have been linked to diverse pathophysiological disorders like urolithiasis, hypertension, electroencephalogram abnormalities and rickets. Importantly, the final amount of Ca²⁺ that is released from the body is determined in the distal part of the nephron, where active Ca²⁺ reabsorption occurs. Here, Transient Receptor Potential Vanilloid member 5 (TRPV5), a highly Ca ²⁺-selective channel, has been recognized as the gatekeeper of active Ca²⁺ reabsorption. The in vivo relevance of TRPV5 has been further investigated by the characterization of TRPV5 knockout (TRPVS^-/-) mice, which exhibit severe disturbances in renal Ca²⁺ handling, such as profound hypercalciuria, intestinal Ca²⁺ hyperabsorption and reduced bone thickness. Hypercalciuria increases the risk of kidney stone formation in these mice. This review highlights our current knowledge about TRPV5-mediated Ca²⁺ reabsorption and emphasizes the physiological relevance and the clinical implications related to the TRPV5^-/- mice model.