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

TY - JOUR

T1 - Hypoxia is not the primary mechanism contributing to exercise-induced proteinuria

AU - Joyce, Kelsley E.

AU - Delamere, John

AU - Bradwell, Susie

AU - Myers, Stephen David

AU - Ashdown, Kimberly

AU - Rue, Carla

AU - Lucas, Samuel J. E.

AU - Thomas, Owen D.

AU - Fountain, Amy

AU - Edsell, Mark

AU - Myers, Fiona

AU - Malein, Will

AU - Imray, Chris

AU - Clarke, Alex

AU - Lewis, Chrisopher T.

AU - Newman, Charles

AU - Johnson, Brian

AU - Cadigan, Patrick

AU - Wright, Alexander

AU - Bradwell, Arthur

N1 - © 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.

PY - 2020/3/26

Y1 - 2020/3/26

N2 - 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.

AB - 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.

KW - altitude

KW - exercise physiology

KW - kidney

KW - mountain

UR - https://www.scopus.com/pages/publications/85083168180

U2 - 10.1136/bmjsem-2019-000662

DO - 10.1136/bmjsem-2019-000662

M3 - Article

C2 - 32341794

AN - SCOPUS:85083168180

SN - 2055-7647

VL - 6

SP - 1

EP - 10

JO - BMJ Open Sport and Exercise Medicine

JF - BMJ Open Sport and Exercise Medicine

IS - 1

M1 - e000662

ER -