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In addition, kidneys participate in systemic gluconeogenesis and in the production or activation of hormones. Acid\u2013base conditions influence all these functions concomitantly. Healthy kidneys properly coordinate a series of physiological responses in the face of acute and chronic acid\u2013base disorders. However, injured kidneys have a reduced capacity to adapt to such challenges. Chronic kidney disease patients are an example of individuals typically exposed to chronic and progressive metabolic acidosis. Their organisms undergo a series of alterations that brake large detrimental changes in the homeostasis of several parameters, but these alterations may also operate as further drivers of kidney damage. Acid\u2013base disorders lead not only to changes in mechanisms involved in acid\u2013base balance maintenance, but they also affect multiple other mechanisms tightly wired to it. In this review article, we explore the basic renal activities involved in the maintenance of acid\u2013base balance and show how they are interconnected to cell energy metabolism and other important intracellular activities. These intertwined relationships have been investigated for more than a century, but a modern conceptual organization of these events is lacking. We propose that pH homeostasis indissociably interacts with central pathways that drive progression of chronic kidney disease, such as inflammation and metabolism, independent of etiology.<\/jats:p>","DOI":"10.1007\/s00424-022-02696-6","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T16:08:02Z","timestamp":1651766882000},"page":"919-934","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Kidney metabolism and acid\u2013base control: back to the basics"],"prefix":"10.1007","volume":"474","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-3601","authenticated-orcid":false,"given":"Pedro Henrique","family":"Imenez Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufar","family":"Mohebbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"2696_CR1","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1038\/2121589a0","volume":"212","author":"GM Aber","year":"1966","unstructured":"Aber GM, Morris LO, Housley E (1966) Gluconeogenesis by the human kidney. 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