Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA166

Poster Communications

Urinary orosomucoid (alpha-1 acid glycoprotein) latex immunoassay is effective for the detection of increased proteinuria associated with altitude and sea-level exercise.

K. Joyce1, S. Bradwell2, J. Delamere3, S. J. Lucas1, S. Myers4, O. Thomas5, A. Fountain6, B. BMRES3, A. Bradwell3

1. School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom. 2. East Surrey Hospital, Redhill, United Kingdom. 3. Medical School, University of Birmingham, Birmingham, United Kingdom. 4. Chichester Institute of Sport, University of Chichester, Chichester, United Kingdom. 5. Taunton and Somerset NHS Foundation Trust, Taunton, United Kingdom. 6. Binding Site Group, Ltd., Birmingham, United Kingdom.

Background: Proteinuria is an established physiologic consequence occurring with exposure to altitude and with exercise. We have recently demonstrated that urinary alpha-1 acid glycoprotein (α1-AGP) correlates better with ascent to altitude compared with albuminuria; however, little research exists regarding the pharmacologic treatment of this pathophysiology at altitude. Objective:To examine the effects of losartan (angiotensin II receptor blocker) on α1-AGP excretion at altitude and with altitude exercise. Methods: Twenty participants took part in this study and were pair-matched for sex, age, and ACE genotype with losartan (100 mg/day) randomly assigned to one participant in each pair. Incremental exercise tests to exhaustion were conducted on a supine cycle ergometer at sea-level (SL) and at altitude (5035 m) in all participants. Urine samples were collected pre-exercise, post-60 min, post-120 min, and post-180 min. Urine samples were analyzed for α1-AGP using a novel latex immunoassay with a range of 0.077- 4.936 mg/L on an Optilite nephelometer. Detectable α1-AGP concentrations were converted to micrograms/minute (μg/min)to account for sample volumes and time elapsed. Independent t-tests and paired t-tests were used to determine differences between groups and within groups, respectively. Results: The immunoassay detected α1-AGP in 97% of the neat samples with only 10% of samples requiring dilution. α1-AGP increased with exercise at SL in both groups (from 3.5 ± 3.9 to 12.3 ± 9.1 μg/minin placebo group, p=0.04; from 1.6 ± 1.6 to 17.9 ± 14.2 ug/min in losartan group, p=0.01), with no significant difference between groups. Pre-exercise α1-AGP increased at altitude in both groups (placebo, Δ1.7 ± 4.0 μg/min; losartan, Δ 0.5 ± 1.0 μg/min), but was not significantly different between groups. Peak exercise power was reduced by ~40% at altitude in both groups (p=0.89). α1-AGP excretion increased with altitude exercise in both groups (placebo, Δ9.33 ± 9.67 μg/min, p=0.01; losartan, Δ6.19 ± 6.04 μg/min, p=0.01). Exercise associated increases in α1-AGP at altitude trended towards being lower (p=0.098) than SL exercise in the losartan group only (58% mean reduction). Odds ratio for exhibiting a reduction in α1-AGP with altitude exercise (compared to SL exercise) was 2.25 greater with losartan. Discussion: The latex immunoassay is an effective method for detecting changes in α1-AGP associated with exercise both at SL and at altitude. Losartan (non-significantly) reduces exercise associated increases in α1-AGP at altitude, possibly due to blocking the AT1 receptor and creating the potential for reductions in heparin sulphate proteoglycans by podocytes, which results in retention of negative charges at the glomerular basement membrane.

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