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Kidney Week

Abstract: TH-PO724

Gender Differences in Calcium Nephrolithiasis

Session Information

Category: Women’s Health and Kidney Diseases

  • 2000 Women’s Health and Kidney Diseases


  • Shin, Samuel, Veterans Affairs Medical Center, Washington, District of Columbia, United States
  • Gombedza, Farai, Veterans Affairs Medical Center, Washington, District of Columbia, United States
  • Awuah boadi, Eugenia, Veterans Affairs Medical Center, Washington, District of Columbia, United States
  • Bandyopadhyay, Bidhan, Veterans Affairs Medical Center, Washington, District of Columbia, United States

Nephrolithiasis continues to develop as a serious problem in the United States and around the world. As yet, the influence of gender on stone formation is unclear. We hypothesized that females are better adapted to higher urine pH than males. This difference could due to higher levels atrial natriuretic peptide (ANP) in pre-menopausal women compared to corresponding men. Interestingly, ANP levels are similar between older women and men. We have previously implicated transient receptor potential canonical 3 (TRPC3), Ca2+ channel, in the proximal tubule (PT), in the regulation of calcium stone formation, and have observed that TRPC3-/- mice show higher Ca2+ secretion and scattered urine crystals compared to wildtype (WT) mice. In the present study, we aimed to examine the gender-based role of pH by alkalization in TRPC3-/- mice predisposed with elevated [Ca2+].


Male and female WT and TRPC3-/- mice were orally administered with either acetazolamide (ACZ), a diuretic for alkalization therapy, and/or calcium gluconate (CaG), a calcium supplement, for 4 weeks. Urine samples were collected weekly and assessed for pH, electrolytes, gene expression and crystals. Serum electrolytes and metabolites were also measured. Kidney tissue was collected for PT cell isolation, Ca2+ imaging and assessed for degree of calcification by birefringence and histopathology.


Urine analysis showed more calcium crystals, higher [Ca2+] and higher pH in female (WT and TRPC3-/-) mice compared to males indicating. Similarly, calcification, fibrotic and inflammatory markers were elevated in female compared to male mice; and in TRPC3-/- compared to WT indicating stone-forming phenotype. PT cells isolated from treated female mice showed a substantial increase in Ca2+ entry when compared to corresponding males suggesting aberrant intracellular Ca2+ regulation.


Higher [Ca2+] and higher pH are related to elevated calcium crystal formation. We have identified gender-based influences on stone-forming phenotypes following alkalization and/or elevated [Ca2+], and our findings suggest that female mice are more susceptible to stone formation under these conditions. Our work contributes to understanding the complex combination of gender, age and lifestyle on the evolving epidemiology of nephrolithiasis. Crucially, we have unraveled a role for gender-specific therapies for kidney stone interventions.


  • NIDDK Support