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Cited by 72Ion Transport and Channel RegulationRenin-Angiotensin System StudiesBlood Pressure and Hypertension Studies

Functional implications of the sex differences in transporter abundance along the rat nephron: modeling and analysis

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Hu, Rui, McDonough, Alicia A., Layton, Anita T.·2019·American Journal of Physiology-Renal Physiology
DOI 10.1152/ajprenal.00352.2019PMC PMC7132321
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Abstract

The goal of the present study was to investigate the functional implications of sexual dimorphism in the pattern of transporters along the rodent nephron as reported by Veiras et al. ( J Am Soc Nephrol 28: 3504–3517, 2017). To do so, we developed sex-specific computational models of water and solute transport along the superficial nephrons from male and female rat kidneys. The models account for the sex differences in the abundance of apical and basolateral transporters, single nephron glomerular filtration rate, and tubular dimensions. Model simulations predict that ~70% and 60% of filtered Na + is reabsorbed by the proximal tubule of male and female rat kidneys, respectively. The lower fractional Na + reabsorption in female kidneys is due primarily to their smaller transport area, lower Na + /H + exchanger activity, and lower claudin-2 abundance, culminating in significantly larger fractional delivery of water and Na + to the downstream nephron segments in female kidneys. Conversely, the female distal nephron exhibits a higher abundance of key Na + transporters, including Na + -K + -Cl − cotransporters, Na + -Cl − cotransporters, and epithelial Na + channels. The higher abundance of transporters accounts for the enhanced water and Na + transport along the female, relative to male, distal nephron, resulting in similar urine excretion between the sexes. Consequently, in response to a saline load, the Na + load delivered distally is greater in female rats than male rats, overwhelming transport capacity and resulting in higher natriuresis in female rats.

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  • There are known sex differences in renal K+ handling, aldosterone concentration, and plasma K+ concentration.

    “We refer to this as a model of a man, instead of more generally as a human model, due to the known sex differences in renal K+ handling [24–26], ALD concentration [27], and plasma K+ concentration [28], all of which affect K+ homeostasis.”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [24]

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Authors
Hu, R., McDonough, A. A., & Layton, A. T.
Affiliations
  • University of Waterloo (CA)
  • University of Southern California (US)
Corresponding author
Layton, Anita T.
ORCID
Venue
American Journal of Physiology-Renal Physiology
Publisher
American Physiological Society
Published
2019-12-01
Volume
317
Issue
6
Pages
F1462-F1474
ISSN
  • 1522-1466 (ISSN-L)
  • 1931-857X
DOI
10.1152/ajprenal.00352.2019
PMC
PMC7132321
OpenAlex
W2978272633
Cited by
72
References
33
Citations by year
2026: 5 · 2025: 5 · 2024: 11 · 2023: 18 · 2022: 14 · 2021: 8 · 2020: 11
FWCI
2.73
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Renal Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canada 150 Research Chair Program
  • HHS | National Institutes of Health (DK106102, DK083785)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
sex differences, renal transporters, nephron, sodium reabsorption, water transport, Na+/H+ exchanger, claudin-2, Na+-K+-2Cl- cotransporter, NaCl cotransporter, epithelial Na+ channel, distal nephron, proximal tubule, glomerular filtration rate, sodium excretion, urinary excretion
MeSH terms
Animals, Carrier Proteins, Female, Glomerular Filtration Rate, Kidney Tubules, Male, Models, Biological, Nephrons, Sex Characteristics, Sodium, Water, Sodium Channels, Sodium-Hydrogen Exchangers, Sodium-Potassium-Chloride Symporters, Rats, Claudins

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