Mulay, S.R.* ; Eberhard, J.N.* ; Pfann, V.* ; Marschner, J.A. ; Darisipudi, M.N.* ; Daniel, C.* ; Romoli, S.* ; Desai, J.* ; Grigorescu, M.* ; Kumar, S.V.* ; Rathkolb, B.* ; Wolf, E.* ; Hrabě de Angelis, M. ; Bäuerle, T.* ; Dietel, B.* ; Wagner, C.A.* ; Amann, K.* ; Eckardt, K.U.* ; Aronson, P.S.* ; Anders, H.J.* ; Knauf, F.*
Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice.
Am. J. Physiol.-Renal Physiol. 310, F785-F795 (2016)
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 weeks 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.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Ckd-mbd ; Cardiovascular ; Hypertension ; Oxalate ; Renal Failure; Unilateral Ureteral Obstruction; Chronic-renal-failure; Acid Nephropathy; Mouse Model; Inflammation; Fibrosis; Progression; Mechanisms; Ckd; Sex
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Language
english
Publication Year
2016
Prepublished in Year
HGF-reported in Year
2016
ISSN (print) / ISBN
1931-857X
e-ISSN
1522-1466
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Volume: 310,
Issue: 8,
Pages: F785-F795
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American Physiological Society
Publishing Place
Bethesda
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0000-00-00
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Reviewing status
Peer reviewed
POF-Topic(s)
30201 - Metabolic Health
90000 - German Center for Diabetes Research
Research field(s)
Genetics and Epidemiology
Helmholtz Diabetes Center
PSP Element(s)
G-500600-001
G-500600-003
G-501900-002
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Erfassungsdatum
2016-02-10