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Estimation of Nephron Number in Whole Kidney using the Acid Maceration Method
Published on: May 22, 2019
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Sex differences in renal acid-base regulation.
Jessica A Dominguez Rieg1,2, Louise Nyrup Odgaard3, Jianxiang Xue4
1Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States.
American Journal of Physiology. Renal Physiology
|September 27, 2025
Summary
Female mice better regulate acid-base balance than males, showing sex-specific differences in kidney transport proteins like NKCC2. This impacts how males and females respond to acid-base challenges.
Area of Science:
- Physiology
- Nephrology
- Biochemistry
Background:
- Renal tubule transport differs between sexes, potentially due to varying transport protein abundance.
- Sex-specific differences in physiological responses and transport protein levels may exist during acid-base challenges.
Purpose of the Study:
- To investigate sex-specific differences in physiological responses and kidney transport protein abundances during acid-base challenges.
- To identify potential sex differences in renal handling of acid-base disturbances.
Main Methods:
- Female and male C57Bl/6J mice were subjected to acid (NH4Cl) or base (NaHCO3) challenges for 8 days.
- Blood and urine parameters were analyzed, and kidney protein abundances were determined using two-way ANOVA.
- Specific focus on the Na+/K+/2Cl- cotransporter, NKCC2.
Main Results:
- Both sexes showed similar decreases in urine pH, blood HCO3-, and base excess during acid challenge, despite lower NH4Cl intake in males.
- Base challenge led to greater increases in blood pH, HCO3-, and base excess in males compared to females.
- Sex significantly affected 7 of 12 tested proteins, treatment affected 7, and NKCC2 showed a significant sex-treatment interaction.
Conclusions:
- Demonstrates significant sex differences in protein abundance within the kidney.
- Reveals differential effects of acid-base challenges on kidney proteins.
- Identifies NKCC2 as a novel and critical protein in acid-base regulation with sex-specific responses.
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