Renal Acid-Base Compensation Demonstrates Plasticity During Incremental Ascent to High Altitude

Abstract

Ascent to high altitude, and the associated hypoxic ventilatory response, imposes an acid-base challenge, namely chronic hypocapnia and respiratory alkalosis. The kidneys act to compensate for this respiratory alkalosis via bicarbonate (HCO3-) excretion in urine to induce a compensatory metabolic acidosis. The time course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We developed a practical index of renal reactivity (RR), indexing the relative change in arterial HCO3- concentration ([HCO3-]a; i.e., response) against the relative change in arterial partial pressure of CO2 (PaCO2; i.e., stimulus) during ascent (i.e., RR=Δ[HCO3-]a/ΔPaCO2). We sought to assess if RR increased over time and with incremental ascent to altitude, and if RR was correlated with relative changes in arterial pH (ΔpHa) throughout ascent. During ascent to 5160m over 10 days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of acid-base variables (Abbott iSTAT portable blood gas/electrolyte analyzer; CG4+ and CHEM8+ cartridges) in lowlanders at 1045/1400m (baseline) and at four different altitudes following one-night sleep: 3440m, 3820m, 4370m and 5160m. At 3820m (day five) and higher, RR significantly increased and plateaued in comparison to 3440m (day three; P<0.04), suggesting plasticity in renal acid-base compensation. At all four altitudes, we observed a strong correlation (range: r=-0.71 to -0.98; P<0.001) between RR and relative ΔpHa from baseline, suggesting that the RR index accurately quantified renal acid-base responsiveness throughout ascent. In conclusion, renal acid-base compensation mechanisms demonstrate plasticity during incremental ascent to high altitude, which was detected using a novel RR index. The extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude. Support or Funding Information: This work was supported by (a) Alberta Government Student Temporary Employment Program, (b) Alberta Innovates Health Solutions Summer Studentship, and (c) Natural Sciences and Engineering Research Council of Canada Discovery grant. *Indicates presente