Recent advances in renal tubular calcium reabsorption

Curr Opin Nephrol Hypertens. 2006 Sep;15(5):524-9. doi: 10.1097/01.mnh.0000242179.38739.fb.

Abstract

Purpose of review: Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Absorption
  • Animals
  • Calcium / metabolism*
  • Calcium Metabolism Disorders / chemically induced
  • Calcium Metabolism Disorders / metabolism
  • Glucuronidase / metabolism
  • Humans
  • Kidney Tubules / metabolism*
  • Sodium Chloride Symporter Inhibitors
  • TRPV Cation Channels / metabolism

Substances

  • Sodium Chloride Symporter Inhibitors
  • TRPV Cation Channels
  • TRPV5 protein, human
  • Glucuronidase
  • klotho protein
  • Calcium