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

Shaelynn M. Zouboules, Hailey C. Lafave, Ken D. O'Halloran, Tom D Brutsaert, Heidi E. Nysten, Cassandra E. Nysten, Craig D. Steinback, Mingma T. Sherpa, Trevor A. Day

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6191-6203
Number of pages13
JournalJournal of Physiology
Issue number24
StatePublished - Dec 15 2018

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Renal reactivity: Acid-base compensation during incremental ascent to high altitude'. Together they form a unique fingerprint.

Cite this