Recent advances in renal tubular calcium reabsorption

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Abstract
Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption. The thiazide diuretics are known for their hypocalciuric effect. Recently, it has been demonstrated that TRPV5-knockout mice, in which active Ca2+ reabsorption in the distal convoluted tubule is completely abolished, show the same sensitivity towards thiazides as wild-type mice. This indicates that thiazide affects Ca2+ reabsorption indirectly via contraction of the extracellular volume, independent of active Ca2+ reabsorption in the distal convoluted tubule, thereby increasing passive paracellular Ca2+ transport in the proximal tubule. Moreover, the antiaging hormone Klotho regulates Ca2+ reabsorption in the distal convoluted tubule via a novel molecular mechanism. Klotho stabilizes the TRPV5 Ca2+ channel in the plasma membrane by deglycosylation of the protein. By showing that thiazide-induced hypercalciuria is due to increased passive Ca2+ reabsorption in the proximal tubule, a long-standing issue has been solved, underlining the importance of proximal paracellular Ca2+ reabsorption. Moreover, the molecular mechanism by which the antiaging hormone Klotho regulates TRPV5 activity may prove to be generally applicable in Klotho-mediated prevention of aging.