{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:12:18Z","timestamp":1788459138352,"version":"build-2803163510"},"reference-count":115,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anara AB"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>In vivo models have been central to understanding hyperoxaluria pathogenesis and to the development of emerging therapeutic strategies, but no single model fully reproduces the complexity of human disease. This narrative review critically evaluates currently available in vivo models of hyperoxaluria and provides a framework for their selection, interpretation, and integration according to the specific phenotype and biological or therapeutic question under investigation. A structured, non-systematic literature search was conducted in PubMed, Web of Science, Scopus, and Google Scholar, with emphasis on peer-reviewed primary studies and relevant reviews addressing experimental models, disease mechanisms, and therapeutic interventions. Chemically and dietary induced, genetic, enteric and microbial, and large-animal models were evaluated with respect to model validity, experimental endpoints, pathophysiological relevance, and translational potential. A central feature of this review is the distinction between related but non-interchangeable phenotypes, including hyperoxaluria, crystalluria, nephrocalcinosis, oxalate nephropathy, and nephrolithiasis. This distinction provides the conceptual basis for comparing models that reproduce different stages or consequences of oxalate exposure rather than treating all calcium oxalate-associated phenotypes as equivalent. Chemically induced models are particularly useful for studying hyperoxaluria, calcium oxalate crystallization, and acute or subacute renal injury, whereas genetic models reproduce specific molecular defects underlying primary hyperoxaluria and support the development of mechanism-based therapies. Enteric and microbial models address intestinal oxalate handling and the gut\u2013kidney axis and are particularly relevant for investigating gut-directed therapeutic strategies. Naturally occurring models may provide complementary insight into chronic clinical phenotypes, whereas large-animal models can facilitate selected translational and experimentally intensive investigations. The reviewed evidence demonstrates that no model can be considered superior. Instead, model selection should be guided by the specific mechanism, phenotype, or therapeutic intervention under investigation. This review therefore proposes a phenotype-oriented and question-driven framework for model selection and interpretation, taking into consideration validity, reproducibility, ethical aspects, and the limits of translational extrapolation.<\/jats:p>","DOI":"10.3390\/ijms27177885","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:13:25Z","timestamp":1788455605000},"page":"7885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Animal Models of Hyperoxaluria and Their Relevance for Fundamental Research and Clinical Practice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5898-3909","authenticated-orcid":false,"given":"Dominika","family":"Szkopek-Zaworska","sequence":"first","affiliation":[{"name":"Large Animal Models Laboratory, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"National Research Institute of Animal Production, 32-083 Balice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Struty\u0144ski","sequence":"additional","affiliation":[{"name":"Anara AB, 23132 Trelleborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-016X","authenticated-orcid":false,"given":"Janine","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Physiology, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-3214","authenticated-orcid":false,"given":"Stefan","family":"Pierzynowski","sequence":"additional","affiliation":[{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Biology, Lund University, 22362 Lund, Sweden"},{"name":"Department of Medical Biology, Institute of Rural Health, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-339X","authenticated-orcid":false,"given":"Kateryna","family":"Pierzynowska","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab\u0142onna, Poland"},{"name":"Anara AB, 23132 Trelleborg, Sweden"},{"name":"Department of Biology, Lund University, 22362 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Jacek","sequence":"additional","affiliation":[{"name":"National Research Institute of Animal Production, 32-083 Balice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41581-022-00643-3","article-title":"Oxalate homeostasis","volume":"19","author":"Ermer","year":"2023","journal-title":"Nat. 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