2. Academic Validation
  3. Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice

Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice

  • Am J Physiol Renal Physiol. 2016 Apr 15;310(8):F785-F795. doi: 10.1152/ajprenal.00488.2015.
Shrikant R Mulay 1,  Jonathan N Eberhard 1,  Victoria Pfann 2,  Julian A Marschner 1,  Murthy N Darisipudi 2,  Christoph Daniel 3,  Simone Romoli 1,  Jyaysi Desai 1,  Melissa Grigorescu 1,  Santhosh V Kumar 1,  Birgit Rathkolb 4 5,  Eckhard Wolf 5,  Martin Hrabě de Angelis 4 6 7,  Tobias Bäuerle 8,  Barbara Dietel 9,  Carsten A Wagner 10,  Kerstin Amann 3,  Kai-Uwe Eckardt 2,  Peter S Aronson 1,  Hans Joachim Anders 1,  Felix Knauf 11 12
Affiliations

Affiliations

  • 1 Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
  • 2 Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 3 Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 4 German Mouse Clinic, Institute of Experimental Genetics, Helmholtz-Zentrum München, Neuherberg, Germany.
  • 5 Institute of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-University München, Munich, Germany.
  • 6 School of Life Science Weihenstephan, Technische Universität München, Freising, Germany.
  • 7 German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • 8 Preclinical Imaging Platform Erlangen, Institute of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 9 Department of Cardiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 10 Zurich Center for Integrative Human Physiology, Zurich, Switzerland; and.
  • 11 Department of Nephrology and Hypertension, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Felix.Knauf@uk-erlangen.de.
  • 12 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
PMID: 26764204 DOI: 10.1152/ajprenal.00488.2015
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.

Keywords

CKD-MBD; cardiovascular; hypertension; oxalate; renal failure.

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