title: Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice.
abstract: Chronic kidney disease (CKD) research is limited by the lack of convenient inducible models mimicking human CKD and its complications in experimental animals. We demonstrate that a soluble oxalate-rich diet induces stable stages of CKD in male and female C57BL/6 mice. Renal histology is characterized by tubular damage, remnant atubular glomeruli, interstitial inflammation, and fibrosis, with the extent of tissue involvement depending on the duration of oxalate feeding. Expression profiling of markers and magnetic resonance imaging findings established to reflect inflammation and fibrosis parallel the histological changes. Within 3 wk, the mice reproducibly develop normochromic anemia, metabolic acidosis, hyperkalemia, FGF23 activation, hyperphosphatemia, and hyperparathyroidism. In addition, the model is characterized by profound arterial hypertension as well as cardiac fibrosis that persist following the switch to a control diet. Together, this new model of inducible CKD overcomes a number of previous experimental limitations and should serve useful in research related to CKD and its complications.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Shrikant R
authors.initials: SR
authors.lastname: Mulay
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Eberhard
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Pfann
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Marschner
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Murthy N
authors.initials: MN
authors.lastname: Darisipudi
authors.affiliation: Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Romoli
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Jyaysi
authors.initials: J
authors.lastname: Desai
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Melissa
authors.initials: M
authors.lastname: Grigorescu
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Santhosh V
authors.initials: SV
authors.lastname: Kumar
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz-Zentrum München, Neuherberg, Germany.|Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.affiliation: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: German Mouse Clinic, Institute of Experimental Genetics, Helmholtz-Zentrum München, Neuherberg, Germany.|School of Life Science Weihenstephan, Technische Universität München, Freising, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.affiliation: Preclinical Imaging Platform Erlangen, Institute of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäuerle
authors.affiliation: Department of Cardiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dietel
authors.affiliation: Zurich Center for Integrative Human Physiology, Zurich, Switzerland; and.
authors.forename: Carsten A
authors.identifier: 0000-0002-9874-8898
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Aronson
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Anders
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Felix.Knauf@uk-erlangen.de.|Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Felix
authors.initials: F
authors.lastname: Knauf
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005355:Fibrosis; D006973:Hypertension / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D019815:Oxalic Acid; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D014511:Uremia / Q000209:etiology* / Q000473:pathology
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D000089703:Fibroblast Growth Factor-23; D019815:Oxalic Acid
keywords: CKD-MBD; cardiovascular; hypertension; oxalate; renal failure