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

Authors :
Awuah Boadi E
Shin S
Choi BE
Ly K
Raub CB
Bandyopadhyay BC
Source :
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2024 May; Vol. 104 (5), pp. 102047. Date of Electronic Publication: 2024 Mar 05.
Publication Year :
2024

Abstract

Sex differences in kidney stone formation are well known. Females generally have slightly acidic blood and higher urine pH when compared with males, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide and calcium gluconate supplementation, respectively, for 4 weeks in wild-type (WT) and moderately hypercalciuric [TRPC3 knockout [KO](-/-)] male and female mice. Our goal was to develop calcium phosphate (CaP) and CaP+ calcium oxalate mixed stones in our animal model to understand the underlying sex-based mechanism of calcium nephrolithiasis. Our results from the analyses of mice urine, serum, and kidney tissues show that female mice (WT and KO) produce more urinary CaP crystals, higher [Ca <superscript>2+</superscript> ], and pH in urine compared to their male counterparts. We identified a sex-based relationship of stone-forming phenotypes (types of stones) in our mice model following urine alkalization/calcium supplementation, and our findings suggest that female mice are more susceptible to CaP stones under those conditions. Calcification and fibrotic and inflammatory markers were elevated in treated female mice compared with their male counterparts, and more so in TRPC3 KO mice compared with their WT counterparts. Together these findings contribute to a mechanistic understanding of sex-influenced CaP and mixed stone formation that can be used as a basis for determining the factors in sex-related clinical studies.<br /> (Published by Elsevier Inc.)

Details

Language :
English
ISSN :
1530-0307
Volume :
104
Issue :
5
Database :
MEDLINE
Journal :
Laboratory investigation; a journal of technical methods and pathology
Publication Type :
Academic Journal
Accession number :
38452902
Full Text :
https://doi.org/10.1016/j.labinv.2024.102047