Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria

Kelsey Joyce, John Delamere, Susie Bradwell, Stephen D Myers, Kimberley Ashdown, Carla Rue, Sam Lucas, Owen D Thomas, Amy Fountain, Mark Edsell, Fiona Myers, Will Malein, Christopher H E Imray, Alex Clarke, Chris Lewis, Charles Newman, Brian Johnson, Patrick Cadigan, Alexander Wright, Jo Bradwell

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1 Citation (Scopus)
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Introduction Proteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria.

Methods Twenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24–48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test.

Results With placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 μg/min; p=0.025) although changes were not correlated (r=−0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001).

Discussion Profound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.
Original languageEnglish
Article numbere000662
Pages (from-to)e000662
Number of pages10
JournalBMJ Open Sport & Exercise Medicine
Issue number1
Publication statusPublished - 26 Mar 2020

Bibliographical note

Funding Information:
This study was supported by the Birmingham Medical Research Expeditionary Society which provided input for the conduct of the research. Patients were not included. Public involvement was limited to recruitment. Notification was given to participants at the time of consent that acquisition of personal data was permitted on request. Permission was also obtained at this time for the dissemination of de-identified data within the research team and only externally when a reasonable request was submitted directly to the corresponding author(s) of the present study within 6 months of its publication. A portion of the cohort was invited to review the research methods for accuracy and readability.

Funding Information:
Contributors All authors listed contributed substantially to the work and by ICMJE 2018 standards meet at minimum satisfy criterion No. 1, No. 3 and No. 4 with additional support for No. 2 provided by KEJ, SJEL, AF, AW, JD and AB.

Funding Information:
Funding The research was partially funded by JABBS Foundation.

Publisher Copyright:
© 2019 Author(s).


  • altitude
  • exercise physiology
  • kidney
  • mountain

ASJC Scopus subject areas

  • Physical Therapy, Sports Therapy and Rehabilitation
  • Orthopedics and Sports Medicine


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