Author(s): JOYCE, K.E., DELAMERE, J., ASHDOWN, K., BRADLEY, C., LUCAS, R., THOMAS, O., LOCK, H., TALKS, B., MALEIN, W., LEWIS, C.T., LETCHFORD, A., CROSS, A., BRADWELL, A.R., LUCAS, S.J.E., Institution: UNIVERSITY OF BIRMINGHAM, Country: UNITED KINGDOM
INTRODUCTION:
Glomerular proteinuria during ascent to altitude is an established physiologic response, although the mechanisms and relevance to acute mountain sickness (AMS) are unclear. Hypotheses include the degree of hypoxia, acid-base disturbances, and changes in systemic pressure. Recent development of more sensitive approaches to detect glomerular proteinuria, such as urinary alpha-1 acid glycoprotein (a1-AGP) assays, improve the ability to examine this question. To evaluate the effects of hypoxia, acid-base disturbances, and changes in systemic pressure on a1-AGP during ascent the present study aimed to: 1) analyse nocturnal saturation, arterial blood gases, systemic blood pressure, and 24-hour a1-AGP and 2) determine whether a1-AGP results were related AMS.
METHODS:
Twenty four-hour urine specimens, systolic (SBP) and diastolic blood pressures (DBP) (manual sphygmomanometer), and nocturnal pulse oximetry (WristOx Model 3150, Nonin) were collected at baseline and each day until reaching 4,800 m (12 days/nights), while arterialised blood was collected at baseline and on rest days during the ascent (earlobe samples, analysed via iSTAT blood gas analyser, Abbott). Urine specimens were analysed with an immunoassay developed for low-concentrations of urinary a1-AGP (0.077–148.2mg/L) on the Optilite auto-analyser (The Binding Site, Ltd., Birmingham, UK). AMS was evaluated using the most recent Lake Louise Scoring (LLS) criteria. Statistical analyses were performed using Prism 8 (Graphpad).
RESULTS:
Twenty-four hour a1-AGP significantly increased with ascent (p=0.0002) and was greatest during the first 24-hours at 4,800 m. PCO2 (p<0.0001), PO2 (p<0.0001), SaO2 (p<0.0001), HCO3- (p<0.0001), and mean nocturnal SpO2 (p<0.0001) significantly decreased while pH (p=0.0173), nocturnal SpO2 variance (p<0.0001), oxygen desaturation index (ODI; p<0.0001), and LLS (p=0.0091) significantly increased with ascent. Mean 24-hour a1-AGP was correlated with altitude (p=0.0003, r=0.888), as expected, and also with changes in: LLS (p=0.0016, r=0.829), SBP (p=0.0009, r=0.852), PCO2 (p=0.0065, r=-0.933), PO2 (p=0.0068, r=-0.932), pH (p=0.0383, r=0.836), tCO2 (p=0.0496, r=-0.812), and SaO2 (p=0.0006, r=-0.981). Mean 24-hour a1-AGP was also correlated with mean nocturnal SpO2 (p<0.0001, r=-0.964), SpO2 variance (p=0.0001, r=0.913), and ODI (p<0.0001, r=0.955).
CONCLUSION:
Findings demonstrate that glomerular proteinuria is strongly related to other physiological perturbations that occur during ascent to high altitude, particularly overnight hypoxia. The relationship between 24-hour a1-AGP and nocturnal desaturations at altitude is similar to the relationship seen in persons with sleep apnoea at sea-level. Thus, aspects of sleep at altitude appear to have the greatest effect on a1-AGP which also presents to be novel biomarker of AMS. This evidence provides support for use the of urinary a1-AGP and nocturnal pulse oximetry as adjuncts to existing AMS diagnostics during ascent to high altitude.