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

Kelsley E. Joyce (Lead / Corresponding author), John Delamere, Susie Bradwell, Stephen David Myers, Kimberly Ashdown, Carla Rue, Samuel J. E. Lucas, Owen D. Thomas, Amy Fountain, Mark Edsell, Fiona Myers, Will Malein, Chris Imray, Alex Clarke, Chrisopher T. Lewis, Charles Newman, Brian Johnson, Patrick Cadigan, Alexander Wright, Arthur Bradwell

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Abstract

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)1-10
Number of pages10
JournalBMJ Open Sport and Exercise Medicine
Volume6
Issue number1
Early online date26 Mar 2020
DOIs
Publication statusPublished - 26 Mar 2020

Keywords

  • altitude
  • exercise physiology
  • kidney
  • mountain

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    Joyce, K. E., Delamere, J., Bradwell, S., Myers, S. D., Ashdown, K., Rue, C., Lucas, S. J. E., Thomas, O. D., Fountain, A., Edsell, M., Myers, F., Malein, W., Imray, C., Clarke, A., Lewis, C. T., Newman, C., Johnson, B., Cadigan, P., Wright, A., & Bradwell, A. (2020). Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria. BMJ Open Sport and Exercise Medicine, 6(1), 1-10. [e000662]. https://doi.org/10.1136/bmjsem-2019-000662