Sex-specific Stone-forming Phenotype in Mice During Hypercalciuria/Urine Alkalinization

Area of Science:

• Nephrology
• Urology
• Biochemistry

Background:

• Sex disparities in kidney stone formation are established but mechanistically unclear.
• Females exhibit higher urine pH and acidity, potentially increasing calcium stone risk.

Purpose of the Study:

• To investigate sex-based mechanisms of calcium phosphate (CaP) and mixed stone formation.
• To analyze the role of sex in hypercalciuria and urine alkalinization models.

Main Methods:

• Utilized wild-type (WT) and TRPC3 knockout (KO) male and female mice.
• Administered acetazolamide and calcium gluconate for 4 weeks to induce stone formation.
• Analyzed urine, serum, and kidney tissues for crystal, ion, and marker levels.

Main Results:

• Female mice produced more urinary CaP crystals, higher urinary calcium (Ca2+), and higher urine pH than males.
• Female mice showed increased susceptibility to CaP stones under tested conditions.
• Elevated calcification, fibrosis, and inflammation markers were observed in treated female mice, particularly TRPC3 KO mice.

Conclusions:

• Identified a sex-based relationship in stone-forming phenotypes, with females more susceptible to CaP stones.
• Findings suggest sex influences CaP and mixed stone formation mechanisms.
• Provides a basis for understanding sex-related factors in clinical nephrolithiasis studies.