Recent advances in renal tubular calcium reabsorption
Current opinion in nephrology and hypertension
Purpose of review Knowledge of renal Ca 2þ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca 2þ reabsorption. Recent findings The thiazide diuretics are known for their hypocalciuric effect. Recently, it has been demonstrated that TRPV5knockout mice, in which active Ca 2þ reabsorption in the distal convoluted tubule is completely abolished, show the same sensitivity towards thiazides as wild-type mice. This indicates
... that thiazide affects Ca 2þ reabsorption indirectly via contraction of the extracellular volume, independent of active Ca 2þ reabsorption in the distal convoluted tubule, thereby increasing passive paracellular Ca 2þ transport in the proximal tubule. Moreover, the antiaging hormone Klotho regulates Ca 2þ reabsorption in the distal convoluted tubule via a novel molecular mechanism. Klotho stabilizes the TRPV5 Ca 2þ channel in the plasma membrane by deglycosylation of the protein. Summary By showing that thiazide-induced hypercalciuria is due to increased passive Ca 2þ reabsorption in the proximal tubule, a long-standing issue has been solved, underlining the importance of proximal paracellular Ca 2þ 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.