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This review draws on the disciplines of evolutionary medicine and bioenergetics to account for the heterogeneous nephron injury that characterizes progressive CKD following episodes of acute kidney injury with incomplete recovery. The evolution of symbiosis in eukaryotes led to the efficiencies of oxidative phosphorylation and the rise of metazoa. Adaptations to ancestral environments are the products of natural selection that have shaped the mammalian nephron with its vulnerabilities to ischemic, hypoxic, and toxic injury. Reproductive fitness rather than longevity has served as the driver of evolution, constrained by available energy and its allocation to homeostatic responses through the life cycle. Metabolic plasticity has evolved in parallel with robustness necessary to preserve complex developmental programs, and adaptations that optimize survival through reproductive years can become maladaptive with aging, reflecting antagonistic pleiotropy. Consequently, environmental stresses promote trade-offs and mismatches that result in cell fate decisions that ultimately lead to nephron loss. Elucidation of the bioenergetic adaptations by the nephron to ancestral and contemporary environments may lead to the development of new biomarkers of kidney disease and new therapies to reduce the global burden of progressive CKD. <\/jats:p>","DOI":"10.1152\/physrev.00029.2022","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T20:07:36Z","timestamp":1680206856000},"page":"2451-2506","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Bioenergetics: the evolutionary basis of progressive kidney disease"],"prefix":"10.1152","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7465-482X","authenticated-orcid":false,"given":"Robert L.","family":"Chevalier","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The University of Virginia, Charlottesville, Virginia, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7208\/chicago\/9780226174310.001.0001"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30045-3"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158765"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.08.036"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03590413"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10851013"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1086\/417048"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-00305-9"},{"key":"B9","volume-title":"The Annotated Origin: A Facsimile of the First Edition of On the Origin of Species","author":"Darwin C","year":"2009"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.10.064"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3540"},{"key":"B12","volume-title":"Biochemical Adaptation. 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