Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA167

Poster Communications

Exercise proteinuria at altitude is reduced by acetazolamide.

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 exhibited with both sea-level exercise and ascent to altitude. Acetazolamide (Az) is a carbonic anhydrase inhibitor that is typically prescribed prior to altitude exposure and has been shown to reduce albuminuria upon ascent. The effects of Az on proteinuria when administered at altitude are unknown. Recently, urinary alpha-1 acid glycoprotein (α1-AGP) has proven to correlate better with ascent than albumin. The combination of exercise and altitude should be a potent stimulus to proteinuria that might be better assessed with urinary α1-AGP concentrations. Objective: To examine the effects of Az on exercise induced α1-AGP excretion at altitude. Methods: Ten subjects participated in this study. An incremental exercise test to exhaustion was conducted at sea-level (SL) and at two separate time points at altitude (both at 5035 m, pre-Az and Az) on a supine cycle ergometer. Az, 125 mg twice daily, was administered immediately after the 1staltitude exercise test for four doses before the 2ndaltitude exercise test. Urine samples were collected pre-exercise, post-60 min, post-120 min, and post-180 min. Urine samples were analysed for α1-AGP using a novel latex immunoassay with a sensitivity range of 0.077 - 4.936 mg/L on an Optilite nephelometer and albumin using radial immunodiffusion. Rates of excretion are reported in order to account for urine sample volumes and time elapsed. Paired samples t-tests were used to evaluate differences in α1-AGP between altitude exercise tests (with a significance threshold of p ≤0.05). Results: The immunoassay successfully detected α1-AGP in 99% of neat samples with only 16% requiring dilution. Mean α1-AGP at post-60 min was significantly different between pre-Az and Az altitude exercise tests (14.8 ± 10.2 vs. 10.7 ± 8.6 μg/min; p=0.05). A significant difference (p=0.029) was also observed between the exercise associated α1-AGP increase (pre-ex to post-60 min) between pre-Az (9.3 ± 9.7 μg/min) and Az (3.6 ± 6.0 μg/min) exercise tests (3-fold reduction), with no difference in peak power between tests. Mean albuminuria at post-60 min was reduced with Az (by 15 %), albeit not a significant difference from pre-Az (p>0.05). Peripheral oxygen saturation at rest (75.1 ± 5.8% vs. 84.0 ± 4.4%; p<0.001) and at exhaustion (69.1 ± 4.5% vs. 75.8 ± 3.8%; p=0.001) were elevated with Az. Discussion: The latex immunoassay is an effective method for detecting changes in urinary α1-AGP, and is a more sensitive marker than albumin for the detection of changes in proteinuria during altitude exercise. Az significantly reduces α1-AGP with altitude exercise; however, further research is warranted to elucidate the mechanisms that are responsible. Conclusion: Increases in α1-AGP associated with altitude exercise are reduced by Az and can be successfully detected using a novel latex immunoassay.

Where applicable, experiments conform with Society ethical requirements