{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:40:29Z","timestamp":1777502429028,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2023\/05641-6"],"award-info":[{"award-number":["2023\/05641-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Almost 10% of the global population suffers from chronic kidney disease (CKD). The inexistence of a therapeutic to restore renal function motivates the scientific community to search for new treatments. The 5\/6 nephrectomy (Nx) rat model is widely used to mimic human CKD, but the impact of strain-specific responses on disease progression remains unclear. Here, we aimed to compare CKD development in Wistar, Lewis, and Fischer rats submitted to the Nx model. In summary, even submitted to the same surgical procedure, the three studied rat strains presented distinct patterns of CKD progression: Wistar rats exhibited faster and sustained renal function loss, with exuberant hypertension, proteinuria, and renal inflammation, being considered as excellent models to study rapidly progressive human nephropathy. Lewis animals, in turn, presented mild low-progressive CKD, which make this rat strain especially useful to simulate intermediate degrees of human CKD and to develop long-term tests. Finally, Fischer rats submitted to Nx did not even develop hypertension, proteinuria, or glomerular damage within 30 days. Moreover, compared to Wistar rats, both Lewis and Fischer animals have a relatively higher basal number of nephrons and a lower number of whole blood leukocytes, which may have contributed to the renoprotection exhibited by these rat strains.<\/jats:p>","DOI":"10.3390\/life16030420","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:01:07Z","timestamp":1772636467000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differences on the Natural Course of Chronic Kidney Disease Progression, Induced by 5\/6 Renal Ablation Model in Three Different Rat Stains: Wistar, Lewis, and Fischer 344"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8657-1287","authenticated-orcid":false,"suffix":"Jr.","given":"Samuel de","family":"Jesus","sequence":"first","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paloma Souza","family":"Noda","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-3890","authenticated-orcid":false,"given":"Ana Laura Rubio","family":"Francini","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Teles Filho","sequence":"additional","affiliation":[{"name":"Renal Division, Faculty of Medicine, Federal University of Alagoas, Maceio 57200-000, AL, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-4329","authenticated-orcid":false,"given":"Mariana Matera","family":"Veras","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental and Experimental Pathology, Department of Pathology, School of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-6463","authenticated-orcid":false,"given":"Ane Claudia Fernandes","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Division of Nephrology, Hypertension and Kidney Transplantation, School of Medicine, University of California, Irvine, CA 92617, USA"},{"name":"Nova Friburgo Health Institute, Fluminense Federal University, Nova Friburgo 28625-650, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene de Lourdes","family":"Noronha","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4425-7708","authenticated-orcid":false,"given":"Camilla","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, Faculty of Medicine, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_2","unstructured":"Vaidya, S.R., and Aeddula, N.R. (2024). Chronic Kidney Disease. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990-2023, and its attributable risk factors: A systematic analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-024-00589-9","article-title":"Chronic kidney disease","volume":"11","author":"Romagnani","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","unstructured":"Zatz, R. (2002). Fisiopatologia Renal, Editora Atheneu. [2nd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1038\/s41598-017-02915-6","article-title":"Innate and Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5\/6 Renal Ablation Model","volume":"7","author":"Fanelli","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yan, Z., Wang, G., and Shi, X. (2021). Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.785375"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41586-020-2941-1","article-title":"Decoding myofibroblast origins in human kidney fibrosis","volume":"589","author":"Kuppe","year":"2021","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF01061973","article-title":"The Wistar Rat as a right choice: Establishing mammalian standards and the ideal of a standardized mammal","volume":"26","author":"Clause","year":"1993","journal-title":"J. Hist. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kuramoto, T., Nakanishi, S., Ochiai, M., Nakagama, H., Voigt, B., and Serikawa, T. (2012). Origins of albino and hooded rats: Implications from molecular genetic analysis across modern laboratory rat strains. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043059"},{"key":"ref_11","unstructured":"Suckow, M.A., Weisbroth, S.H., and Franklin, C.L. (2006). The Rat as an Animal Model in Biomedical Research. The Laboratory Rat, Academic Press. [2nd ed.]."},{"key":"ref_12","first-page":"100051","article-title":"Mesenchymal Stem Cells Derived from Adipose Tissue Ameliorate Chronic Allograft Rejection in the Long Term in a Rat Experimental Model of Kidney Transplantation","volume":"6","author":"Pepineli","year":"2020","journal-title":"J. Stem Cells Res. Dev. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ddmod.2010.08.002","article-title":"Models of chronic kidney disease","volume":"7","author":"Yang","year":"2010","journal-title":"Drug Discov. Today Dis. Models"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.kint.2023.03.007","article-title":"International Society of Nephrology first consensus guidance for preclinical animal studies in translational nephrology","volume":"104","author":"Nangaku","year":"2023","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.etp.2005.09.005","article-title":"Suitability of 5\/6 nephrectomy (5\/6NX) for the induction of interstitial renal fibrosis in rats\u2014Influence of sex, strain, and surgical procedure","volume":"57","author":"Fleck","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1093\/ndt\/gft071","article-title":"Animal models of chronic kidney disease: Useful but not perfect","volume":"28","author":"Becker","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F580","DOI":"10.1152\/ajprenal.00042.2011","article-title":"Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation","volume":"301","author":"Fanelli","year":"2011","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1097\/00007890-200301150-00010","article-title":"Combination therapy of mycophenolate mofetil and rapamycin in prevention of chronic renal allograft rejection in the rat","volume":"75","author":"Jolicoeur","year":"2003","journal-title":"Transplantation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1097\/00007890-200202270-00032","article-title":"Expression of growth arrest\u2013specific gene 6 and its receptors in a rat model of chronic renal transplant rejection","volume":"73","author":"Yin","year":"2002","journal-title":"Transplantation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/00007890-200002270-00006","article-title":"SDZ-RAD prevents manifestation of chronic rejection in rat renal allografts","volume":"69","author":"Zou","year":"2000","journal-title":"Transplantation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/TP.0000000000002204","article-title":"Tofacitinib Halts Progression of Graft Dysfunction in a Rat Model of Mixed Cellular and Humoral Rejection","volume":"102","author":"Rovira","year":"2018","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1046\/j.1523-1755.1999.055003945.x","article-title":"Mycophenolate mofetil prevents the progressive renal failure induced by 5\/6 renal ablation in rats","volume":"55","author":"Romero","year":"1999","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1111\/j.1523-1755.2004.00496.x","article-title":"Calcium citrate ameliorates the progression of chronic renal injury","volume":"65","author":"Gadola","year":"2004","journal-title":"Kidney Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"F1005","DOI":"10.1152\/ajprenal.00195.2024","article-title":"5\/6 Nephrectomy impairs acute kaliuretic responses and predisposes to postprandial hyperkalemia","volume":"327","author":"Wei","year":"2024","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1046\/j.1523-1755.2000.00140.x","article-title":"Mycophenolate mofetil reduces myofibroblast infiltration and collagen III deposition in rat remnant kidney","volume":"58","author":"Badid","year":"2000","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_27","first-page":"87","article-title":"Determina\u00e7\u00e3o do Tamanho da Amostra em Pesquisas Experimentais na \u00c1rea de Sa\u00fade","volume":"29","author":"Weyne","year":"2004","journal-title":"Arq. M\u00e9dicos ABC"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.22237\/jmasm\/1304222940","article-title":"Sample Size Considerations for Multiple Comparison Procedures in ANOVA","volume":"10","author":"Brooks","year":"2011","journal-title":"J. Mod. Appl. Stat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5111782","DOI":"10.1155\/2022\/5111782","article-title":"Synergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKD","volume":"2022","author":"Maires","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Noda, P., Francini, A.L.R., Teles, F., J\u00fanior, S.J., Fonseca, F.L.A., Borges, F.T., Sobrinho, A.C., Taniwaki, N., Noronha, I.L., and Fanelli, C. (2025). Extracellular Vesicles (EVs) Derived from Mesenchymal Stem Cells (MSCs) as Adjuvants in the Treatment of Chronic Kidney Disease (CKD). Cells, 14.","DOI":"10.3390\/cells14060434"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1258\/la.2011.011021","article-title":"A simple procedure for estimation of total body surface area and determination of a new value of Meeh\u2019s constant in rats","volume":"46","author":"Gouma","year":"2012","journal-title":"Lab. Anim."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"F639","DOI":"10.1152\/ajprenal.00398.2021","article-title":"Comparison of the surgical resection and infarct 5\/6 nephrectomy rat models of chronic kidney disease","volume":"322","author":"Adam","year":"2022","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.kisu.2017.07.004","article-title":"Genetic and environmental risk factors for chronic kidney disease","volume":"7","author":"Obrador","year":"2017","journal-title":"Kidney Int. Suppl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.12659\/MSM.903820","article-title":"Role of Nitric Oxide Pathway in Development and Progression of Chronic Kidney Disease in Rats Sensitive and Resistant to its Occurrence in an Experimental Model of 5\/6 Nephrectomy","volume":"23","author":"Saracyn","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1161\/CIRCRESAHA.122.321762","article-title":"Hypertension as Cardiovascular Risk Factor in Chronic Kidney Disease","volume":"132","author":"Burnier","year":"2023","journal-title":"Circ. Res."},{"key":"ref_36","first-page":"e86230","article-title":"Effect of Blood Pressure Control on Cardiovascular Events in Patients with Chronic Kidney Disease: A Systematic Review","volume":"17","author":"Ahmed","year":"2025","journal-title":"Cureus"},{"key":"ref_37","unstructured":"Steckler, T., Kalin, N.H., and Reul, J.M.H.M. (2005). Handbook of Stress and the Brain, Elsevier."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1023\/A:1021644002588","article-title":"Behavioral and neurochemical differences between Fischer 344 and Harlan-Wistar rats raised identically","volume":"29","author":"Rex","year":"1999","journal-title":"Behav. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/nlme.2001.4040","article-title":"Fischer 344 and wistar rats differ in anxiety and habituation but not in water maze performance","volume":"78","author":"Bert","year":"2002","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rath, T. (2018). Inflammation in nonimmune-mediated chronic kidney disease. Chronic Kidney Disease\u2014From Pathology to Clinical Improvements, IntechOpen.","DOI":"10.5772\/66239"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1365-2613.2011.00764.x","article-title":"Fibroblasts and myofibroblasts in renal fibrosis","volume":"92","author":"Meran","year":"2011","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117079","DOI":"10.1016\/j.biopha.2024.117079","article-title":"The role of macrophages in fibrosis of chronic kidney disease","volume":"177","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_43","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age to Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1590\/S0102-67202012000100011","article-title":"Rat\u2019s age versus human\u2019s age: What is the relationship?","volume":"25","author":"Andreollo","year":"2012","journal-title":"Arq. Bras. Cir. Dig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1383728","DOI":"10.3389\/fnins.2024.1383728","article-title":"A coming-of-age story: Adult neurogenesis or adolescent neurogenesis in rodents?","volume":"18","author":"Arellano","year":"2024","journal-title":"Front. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pedneo.2011.02.007","article-title":"Reciprocal changes of renal neuronal nitric oxide synthase-\u03b1 and -\u03b2 associated with renal progression in a neonatal 5\/6 nephrectomized rat model","volume":"52","author":"Tain","year":"2011","journal-title":"Pediatr. Neonatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00004872-200018020-00001","article-title":"An intact renin-angiotensin system is a prerequisite for normal renal development","volume":"18","author":"Guron","year":"2000","journal-title":"J. Hypertens."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1007\/s11695-011-0377-2","article-title":"Impaired laparotomy wound healing in obese rats","volume":"21","author":"Xing","year":"2011","journal-title":"Obes. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fukunaga, S., and Fujita, Y. (2023). Low glomerular number at birth can lead to the development of chronic kidney disease. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1120801"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"717","DOI":"10.4103\/1319-2442.292305","article-title":"Birth Weight and Susceptibility to Chronic Kidney Disease","volume":"31","author":"Hannawi","year":"2020","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_51","unstructured":"Charles River Laboratories (2008). Wistar Rat Model Information Sheet, Charles River Laboratories. Available online: https:\/\/assets.www.criver.com\/storage-account-container\/resources\/doc_a\/rm_d_Wistar_Rat.pdf."},{"key":"ref_52","unstructured":"Charles River Laboratories (2011). Lewis Rat Clinical Pathology Data, Charles River Laboratories. Available online: https:\/\/azupcriversitestorage01.blob.core.windows.net\/storage-account-container\/resources\/rm_rm_r_Lewis_Rat_clinical_pathology_data.pdf."},{"key":"ref_53","unstructured":"Charles River Laboratories (2009). CDF (Fischer) Rat Clinical Pathology Data, Charles River Laboratories. Available online: https:\/\/assets.www.criver.com\/storage-account-container\/resources\/doc_a\/rm_rm_r_CDF_Fisher_Rat_clinical_pathology_data.pdf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/PSY.0000000000000520","article-title":"Stress and Addiction: When a Robust Stress Response Indicates Resiliency","volume":"80","year":"2018","journal-title":"Psychosom. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/cei.13119","article-title":"The role of the immune system in kidney disease","volume":"192","author":"Tecklenborg","year":"2018","journal-title":"Clin. Exp. Immunol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/3\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:14:12Z","timestamp":1772637252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/3\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["life16030420"],"URL":"https:\/\/doi.org\/10.3390\/life16030420","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]}}}