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We undertook a systematic study of the effects of dietary salt intake on glomerular filtration rate (GFR) and tubular Na<jats:sup>+<\/jats:sup> reabsorption. We examined the renal adaptive response in mice subjected to 7\u00a0days of a low sodium diet (LSD) containing 0.01% Na<jats:sup>+<\/jats:sup>, a normal sodium diet (NSD) containing 0.18% Na<jats:sup>+<\/jats:sup> and a moderately high sodium diet (HSD) containing 1.25% Na<jats:sup>+<\/jats:sup>. As expected, LSD did not alter measured GFR and increased the abundance of total and cell\u2010surface NHE3, NKCC2, NCC, \u03b1\u2010ENaC and cleaved \u03b3\u2010ENaC compared to NSD. Mathematical modelling predicted that tubular Na<jats:sup>+<\/jats:sup> reabsorption increased in the proximal tubule but decreased in the distal nephron because of diminished Na<jats:sup>+<\/jats:sup> delivery. This prediction was confirmed by the natriuretic response to diuretics targeting the thick ascending limb, the distal convoluted tubule or the collecting system. On the other hand, HSD did not alter measured GFR but decreased the abundance of the aforementioned transporters compared to NSD. Mathematical modelling predicted that tubular Na<jats:sup>+<\/jats:sup> reabsorption decreased in the proximal tubule but increased in distal segments with lower transport efficiency with respect to O<jats:sub>2<\/jats:sub> consumption. This prediction was confirmed by the natriuretic response to diuretics. The activity of the metabolic sensor adenosine monophosphate\u2010activated protein kinase (AMPK) was related to the changes in tubular Na<jats:sup>+<\/jats:sup> reabsorption. Our data show that fractional Na<jats:sup>+<\/jats:sup> reabsorption is distributed differently according to dietary Na<jats:sup>+<\/jats:sup> intake and induces changes in tubular O<jats:sub>2<\/jats:sub> consumption and sodium transport efficiency.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274927","type":"journal-article","created":{"date-parts":[[2017,9,21]],"date-time":"2017-09-21T04:23:02Z","timestamp":1505967782000},"page":"6905-6922","source":"Crossref","is-referenced-by-count":47,"title":["Dietary sodium induces a redistribution of the tubular metabolic workload"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6488-2757","authenticated-orcid":false,"given":"Khalil","family":"Udwan","sequence":"first","affiliation":[{"name":"Department of Cellular Physiology and Metabolism University of Geneva  CMU, 1 Rue Michel\u2010Servet CH\u20101211 Geneva 4 Switzerland"},{"name":"National Centre of Competence in Research NCCRKidney  CH 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