Refining the Mouse Subtotal Nephrectomy in Male 129S2/SV Mice for Consistent Modeling of Progressive Kidney Disease With Renal Inflammation and Cardiac Dysfunction.
cardiac hypertrophy
chronic kidney disease (CKD)
modeling disease
monocytes/macrophages
renal fibrosis and inflammation
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2019
2019
Historique:
received:
24
07
2019
accepted:
14
10
2019
entrez:
6
12
2019
pubmed:
6
12
2019
medline:
6
12
2019
Statut:
epublish
Résumé
Chronic kidney disease (CKD) is prevalent worldwide and is associated with significant co-morbidities including cardiovascular disease (CVD). Traditionally, the subtotal nephrectomy (remnant kidney) experimental model has been performed in rats to model progressive renal disease. The model experimentally mimics CKD by reducing nephron number, resulting in renal insufficiency. Presently, there is a lack of translation of pre-clinical findings into successful clinical results. The pre-clinical nephrology field would benefit from reproducible progressive renal disease models in mice in order to avail of more widely available transgenics and experimental tools to dissect mechanisms of disease. Here we evaluate if a simplified single step subtotal nephrectomy (STNx) model performed in the 129S2/SV mouse can recapitulate the renal and cardiac changes observed in patients with CKD in a reproducible and robust way. The single step STNx surgery was well-tolerated and resulted in clinically relevant outcomes including hypertension, increased urinary albumin:creatinine ratio, and significantly increased serum creatinine, phosphate and urea. STNx mice developed significant left ventricular hypertrophy without reduced ejection fraction or cardiac fibrosis. Analysis of intra-renal inflammation revealed persistent recruitment of Ly6C
Identifiants
pubmed: 31803059
doi: 10.3389/fphys.2019.01365
pmc: PMC6872545
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1365Subventions
Organisme : Medical Research Council
ID : MR/M011542/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 O’Sullivan, Finnie, Teenan, Cairns, Boyd, Bailey, Thomson, Hughes, Bénézech, Conway and Denby.
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