Renal reactivity: acid‐base compensation during incremental ascent to high altitude

Abstract

Key points Ascent to high altitude imposes an acid‐base challenge in which renal compensation is integral for maintaining pH homeostasis, facilitating acclimatization and helping prevent mountain sicknesses. The time‐course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We created a novel index that accurately quantifies renal acid‐base compensation, which may have laboratory, fieldwork and clinical applications. Using this index, we found that renal compensation increased and plateaued after 5 days of incremental altitude exposure, suggesting plasticity in renal acid‐base compensation mechanisms. The time‐course and extent of plasticity in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at 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 (P aC O2) (i.e. renal stimulus) during incremental ascent to altitude (Δ[ HC normalO3−]normala/ΔP aC normalO2). We aimed to assess whether: (i) RR magnitude was inversely correlated with relative changes in arterial pH (ΔpHa) 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 ΔpHa 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.

The exhausting work of acclimating to chronically elevated CO2

“…; Zouboules et al . ), exposure to chronic elevated CO 2 also has acid–base implications, albeit in the opposite direction (see Fig. ).…”

“…Similar to the HVR-mediated hypocapnia and the resulting respiratory alkalosis associated with high altitude ascent (e.g. Forster et al 1975;Zouboules et al 2018), exposure to chronic elevated CO 2 also has acid-base implications, albeit in the opposite direction (see Fig. 1).…”

“…Thus, our integrative illustrations of idealized responses to chronic CO 2 perturbations (see Fig. 1), guided by data from Forster et al (1975) and Zouboules et al (2018) (for hypoxic hypocapnia) and Schaefer et al (1963) and Burgraff et al (2018) (for relative hypercapnia), are largely speculative. However, the stimuli and responses illustrated are instructive toward an integrative understanding of chronic acid-base perturbations.…”

“…Due to its relatively high solubility in body fluids, CO 2 retention represents a challenge for acid–base homeostasis, which is maintained in concert by the respiratory and renal systems (Zouboules et al . ).…”

“…Elimination of metabolically derived CO 2 is critically important to air breathing organisms. Due to its relatively high solubility in body fluids, CO 2 retention represents a challenge for acid-base homeostasis, which is maintained in concert by the respiratory and renal systems (Zouboules et al 2018).…”