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

Authors

Eugenia Awuah Boadi, Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC.
Samuel Shin, Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC; Department of Biomedical Engineering, The Catholic University of America, Washington DC.
Bok-Eum Choi, Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC.
Khanh Ly, Department of Biomedical Engineering, The Catholic University of America, Washington DC.
Christopher B. Raub, Department of Biomedical Engineering, The Catholic University of America, Washington DC.
Bidhan C. Bandyopadhyay, Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC; Department of Biomedical Engineering, The Catholic University of America, Washington DC; Division of Renal Diseases and Hypertension, Department of Medicine, The George Washington University, Washington DC. Electronic address: bidhan.bandyopadhyay@va.gov.

Document Type

Journal Article

Publication Date

3-5-2024

Journal

Laboratory investigation; a journal of technical methods and pathology

Volume

104

Issue

5

DOI

10.1016/j.labinv.2024.102047

Keywords

calcium nephrolithiasis; hypercalciuria; oxidative stress; proximal tubular acidosis; sex differences; urinary stones

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], 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.

APA Citation

Awuah Boadi, Eugenia; Shin, Samuel; Choi, Bok-Eum; Ly, Khanh; Raub, Christopher B.; and Bandyopadhyay, Bidhan C., "Sex-specific Stone-forming Phenotype in Mice During Hypercalciuria/Urine Alkalinization" (2024). GW Authored Works. Paper 4559.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4559

Department

Medicine