Renal reactivity: acid‐base compensation 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 impart a relative compensatory metabolic acidosis through the elimination of bicarbonate (HCO₃^- ) in urine. The time-course and extent of plasticity of the renal response during incremental ascent is unclear. We developed an index of renal reactivity (RR), indexing the relative change in arterial bicarbonate concentration ([HCO₃^- ]_a ) (i.e. renal response) against the relative change in arterial pressure of CO₂ ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:math> ) (i.e. renal stimulus) during incremental ascent to altitude ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>Δ</mml:mi><mml:msub><mml:mrow><mml:mo>[</mml:mo><mml:mi>HC</mml:mi><mml:msup><mml:mrow><mml:msub><mml:mi>O</mml:mi><mml:mn>3</mml:mn></mml:msub></mml:mrow><mml:mo>-</mml:mo></mml:msup><mml:mo>]</mml:mo></mml:mrow><mml:mi>a</mml:mi></mml:msub><mml:mo>/</mml:mo><mml:mi>Δ</mml:mi><mml:msub><mml:mi>P</mml:mi><mml:mrow><mml:mi>aC</mml:mi><mml:msub><mml:mi>O</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:msub></mml:mrow></mml:math> ). We aimed to assess whether: (i) RR magnitude was inversely correlated with relative changes in arterial pH (ΔpH_a ) with ascent and (ii) RR increased over time and altitude exposure (i.e. plasticity). During ascent to 5160 m over 10 days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of blood gas/acid-base variables in lowlanders at 1045/1400 m and after 1 night of sleep at 3440 m (day 3), 3820 m (day 5), 4240 m (day 7) and 5160 m (day 10) during ascent. At 3820 m and higher, RR significantly increased and plateaued compared to 3440 m (P < 0.04), suggesting plasticity in renal acid-base compensations. At all altitudes, we observed a strong negative correlation (r ≤ -0.71; P < 0.001) between RR and ΔpH_a from baseline. Renal compensation plateaued after 5 days of altitude exposure, despite subsequent exposure to higher altitudes. The time-course, extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.