Hypoxia Is Not The Primary Mechanism Contributing To Exercise-Induced Proteinuria

IntroductionProteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (alpha 1-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.MethodsTwenty 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 similar to 1hour). Acetazolamide (125mg two times per day) was administrated immediately after this test for 48hours until the second altitude exercise test.ResultsWith placebo, post-exercise alpha 1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting alpha 1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise alpha 1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO(2)) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.39.7 vs 3.6 +/- 6.0 mu g/min; p=0.025) although changes were not correlated (r=-0.10) with significant improvements in SpO(2) (69.1%+/- 4.5% vs 75.8%+/- 3.8%; p=0.001).DiscussionProfound 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.