Sex differences in proximal and distal nephron function contribute to the mechanism of idiopathic hypercalcuria in calcium stone formers

Am J Physiol Regul Integr Comp Physiol. 2015 Jul 1;309(1):R85-92. doi: 10.1152/ajpregu.00071.2015. Epub 2015 May 6.


Idiopathic hypercalciuria (IH) is a common familial trait among patients with calcium nephrolithiasis. Previously, we have demonstrated that hypercalciuria is primarily due to reduced renal proximal and distal tubule calcium reabsorption. Here, using measurements of the clearances of sodium, calcium, and endogenous lithium taken from the General Clinical Research Center, we test the hypothesis that patterns of segmental nephron tubule calcium reabsorption differ between the sexes in IH and normal subjects. When the sexes are compared, we reconfirm the reduced proximal and distal calcium reabsorption. In IH women, distal nephron calcium reabsorption is decreased compared to normal women. In IH men, proximal tubule calcium reabsorption falls significantly, with a more modest reduction in distal calcium reabsorption compared to normal men. Additionally, we demonstrate that male IH patients have lower systolic blood pressures than normal males. We conclude that women and men differ in the way they produce the hypercalciuria of IH, with females reducing distal reabsorption and males primarily reducing proximal tubule function.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Blood Pressure
  • Calcium / urine*
  • Case-Control Studies
  • Fasting / urine
  • Female
  • Humans
  • Hypercalciuria / metabolism*
  • Hypercalciuria / physiopathology
  • Hypercalciuria / urine
  • Kidney Calculi / metabolism*
  • Kidney Calculi / physiopathology
  • Kidney Calculi / urine
  • Kidney Tubules, Distal / metabolism*
  • Kidney Tubules, Distal / physiopathology
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / physiopathology
  • Magnesium / urine
  • Male
  • Middle Aged
  • Models, Biological
  • Postprandial Period
  • Renal Reabsorption*
  • Sex Factors
  • Sodium / urine
  • Time Factors
  • Young Adult


  • Sodium
  • Magnesium
  • Calcium

Supplementary concepts

  • Hypercalciuria, Absorptive, 2