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

Research output: Contribution to journalArticlepeer-review


  • Kelsey Joyce
  • John Delamere
  • Susie Bradwell
  • Stephen D Myers
  • Kimberley Ashdown
  • Carla Rue
  • 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

External organisations

  • Birmingham Medical Research Expeditionary Society
  • University of Warwick


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.

Bibliographic note

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


Original languageEnglish
Article numbere000662
Pages (from-to)1-10
Number of pages10
JournalBMJ Open Sport & Exercise Medicine
Issue number1
Publication statusPublished - 26 Mar 2020


  • altitude, exercise physiology, kidney, mountain