Recent advances in renal tubular calcium reabsorption.
OBJECTIVE
Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption.


RESULTS
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.


CONCLUSIONS
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.
Mensenkamp
Arjen R
AR
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands.
Hoenderop
Joost G J
JG
Bindels
René J M
RJ
D000042:Absorption; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002128:Calcium Metabolism Disorders / Q000139:chemically induced / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D000090265:Klotho Proteins; D049993:Sodium Chloride Symporter Inhibitors; D050916:TRPV Cation Channels / Q000378:metabolism
D049993:Sodium Chloride Symporter Inhibitors; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium