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

Abstract

IntroductionProteinuria 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.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 ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test.ResultsWith 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).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.

Postexercise urinary alpha-1 acid glycoprotein is not dependent on hypoxia

“…The coupling between desaturation and attenuated postexercise α1-AGP excretion in HYP observed in this study supports earlier cycling-based studies that have demonstrated similar reductions ( 7 ) or unchanged postexercise excretion in hypoxia ( 28 ). The present observations were attributed to concomitant reductions in exercise performance known to accompany hypoxic exercise ( 29 ), which have, in part, been attributed to reductions in blood flow to the working limbs ( 30 ).…”

“…Normality of distribution was assessed using Shapiro–Wilk test for each outcome measure with data log-transformed where possible and outliers removed (using ROUT method) where appropriate (for normally distributed data) before analysis. For reference, raw α1-AGP excretion data were reported, however, analyses for urinary α1-AGP were conducted using log-transformed values as previously described ( 7 ).…”

“…Glomerular proteinuria is a transient physiological phenomenon that occurs in healthy individuals following exercise ( 1 ) and during ascent to altitude ( 2 , 3 ). Exhibited across a range of physical activities [e.g., swimming ( 4 ), running ( 5 ), and rowing ( 6 )], it can be characterized by increases in urinary albumin or alpha-1 acid glycoprotein (α1-AGP; 1 , 7 ), the latter being a potentially more sensitive marker of proteinuria ( 3 ). Exercise intensity ultimately dictates the degree of the postexercise increases ( 8 , 9 ), although the mechanism(s) for this are not well understood.…”

Effect of losartan on performance and physiological responses to exercise at high altitude (5035 m)

“…Further details of participant genotype pairing, losartan administration and ascent profile have been previously published as part of another study conducted on this expedition. 15 …”

“…Further details of participant genotype pairing, losartan administration and ascent profile have been previously published as part of another study conducted on this expedition. 15 Baseline and daily measures Baseline measures of BP and exercise performance were recorded at sea-level and before losartan/placebo administration (~4 weeks prior to ascent). During ascent, measures of resting systolic and diastolic BPs (SBP and DBP) were collected each morning using a manual sphygmomanometer as part of the routine medical examination.…”