Renal reactivity: Acid-base compensation during incremental ascent to high altitude

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 (HCO ₃ ⁻ ) 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 ([HCO ₃ ⁻ ] _a ) (i.e. renal response) against the relative change in arterial pressure of CO ₂ (P _aCO2 ) (i.e. renal stimulus) during incremental ascent to altitude (Δ[HCO ₃ ⁻ ] _a /ΔP _aCO2 ). 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.