{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:46:03Z","timestamp":1792226763560,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2018,10,28]],"date-time":"2018-10-28T00:00:00Z","timestamp":1540684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102016\u201004915"],"award-info":[{"award-number":["RGPIN\u20102016\u201004915"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ascent to high altitude imposes an acid\u2010base challenge in which renal compensation is integral for maintaining pH homeostasis, facilitating acclimatization and helping prevent mountain sicknesses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The time\u2010course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We created a novel index that accurately quantifies renal acid\u2010base compensation, which may have laboratory, fieldwork and clinical applications.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using this index, we found that renal compensation increased and plateaued after 5\u00a0days of incremental altitude exposure, suggesting plasticity in renal acid\u2010base compensation mechanisms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The time\u2010course and extent of plasticity in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Ascent to high altitude, and the associated hypoxic ventilatory response, imposes an acid\u2010base challenge, namely chronic hypocapnia and respiratory alkalosis. The kidneys impart a relative compensatory metabolic acidosis through the elimination of bicarbonate (HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>) in urine. The time\u2010course 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<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>]<jats:sub>a<\/jats:sub>) (i.e. renal response) against the relative change in arterial pressure of CO<jats:sub>2<\/jats:sub> (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp13259-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp13259:tjp13259-math-0001\"\/>) (i.e. renal stimulus) during incremental ascent to altitude (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp13259-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp13259:tjp13259-math-0002\"\/>). We aimed to assess whether: (i) RR magnitude was inversely correlated with relative changes in arterial pH (\u0394pH<jats:sub>a<\/jats:sub>) with ascent and (ii) RR increased over time and altitude exposure (i.e. plasticity). During ascent to 5160\u00a0m over 10\u00a0days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of blood gas\/acid\u2010base variables in lowlanders at 1045\/1400\u00a0m and after 1\u00a0night of sleep at 3440\u00a0m (day 3), 3820\u00a0m (day 5), 4240\u00a0m (day 7) and 5160\u00a0m (day 10) during ascent. At 3820\u00a0m and higher, RR significantly increased and plateaued compared to 3440\u00a0m (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.04), suggesting plasticity in renal acid\u2010base compensations. At all altitudes, we observed a strong negative correlation (<jats:italic>r<\/jats:italic>\u00a0\u2264\u00a0\u22120.71; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) between RR and \u0394pH<jats:sub>a<\/jats:sub> from baseline. Renal compensation plateaued after 5\u00a0days of altitude exposure, despite subsequent exposure to higher altitudes. The time\u2010course, extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276973","type":"journal-article","created":{"date-parts":[[2018,9,29]],"date-time":"2018-09-29T13:24:50Z","timestamp":1538227490000},"page":"6191-6203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Renal reactivity: acid\u2010base compensation during incremental ascent to high altitude"],"prefix":"10.1113","volume":"596","author":[{"given":"Shaelynn M.","family":"Zouboules","sequence":"first","affiliation":[{"name":"Department of Biology Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey C.","family":"Lafave","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-1153","authenticated-orcid":false,"given":"Ken D.","family":"O'Halloran","sequence":"additional","affiliation":[{"name":"University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom D.","family":"Brutsaert","sequence":"additional","affiliation":[{"name":"University of Syracuse  Syracuse, NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi E.","family":"Nysten","sequence":"additional","affiliation":[{"name":"Red Deer Regional Hospital  Red Deer Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra E.","family":"Nysten","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Science and Technology Mount Royal University  Calgary Alberta 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