Adenine-induced hyperphosphatemia in a murine model of renal insufficiency

dc.contributor.author Bobeck, Elizabeth
dc.contributor.author Piccione, Michelle
dc.contributor.author Bobeck, Elizabeth
dc.contributor.author Bishop, Jeff
dc.contributor.author Fulmer, Tyler
dc.contributor.author Schwahn, Denise
dc.contributor.author Helvig, Christian
dc.contributor.author Petkovich, Martin
dc.contributor.author Cook, Mark
dc.contributor.department Animal Science
dc.date 2018-03-07T15:15:30.000
dc.date.accessioned 2020-06-29T23:40:20Z
dc.date.available 2020-06-29T23:40:20Z
dc.date.copyright Sun Jan 01 00:00:00 UTC 2017
dc.date.issued 2017-01-01
dc.description.abstract <p>Hyperphosphatemia in chronic kidney disease (CKD) patients is a risk factor for cardiovascular events, progressive kidney failure, and mortality. Improved therapeutic interventions to control hyperphosphatemia depend greatly on robust animal models that recapitulate the CKD disease process. Murine-based models of CKD as compared to rat models present significant advantages due to available genetic knockout lines that permit mechanistic dissection of CKD etiologies. The rat adenine model of renal failure has been extensively studied, and studies are now emerging describing adenine-induced renal failure in murine models. However, these newly developed murine models have not fully described the responses to calcitriol and phosphate binders, and the reported effects of adenine on serum phosphate is often lacking in murine models. Therefore, the objectives of this study were: 1) To induce hyperphosphatemia in mice using adenine with minimal mortality, and 2) Report the influence of calcitriol and phosphate binders on the disease process through measurement of serum phosphate and histology. In one approach, C57BL/6 male mice gavaged with 4 or 6 mg adenine/day, as compared to 0 mg adenine/day developed hyperphosphatemia, with low mortality. In a second approach, calcitriol exacerbated adenine-induced increases in serum phosphate at day 7 of adenine administration (p<0.05). Notably, adenine treated mice had 4-fold increased stomach weights vs. non-adenine treated mice (p<0.0001). The addition of a phosphate binder (experiment 3, sevelamer hydrochloride) was ineffective at preventing an adenine-induced increase in blood phosphate, a finding that likely resulted from adenine’s inhibition of gastric emptying. We report the successful use of adenine to induce hyperphosphatemia, that the hyperphosphatemic status is exacerbated by calcitriol, and a limitation of the model for studying oral therapies for hyperphosphatemia.</p>
dc.description.comments <p>This article is published as EA Bobeck, ML Piccione, JW Bishop, TG Fulmer, DJ Schwahn, C Helvig, M Petkovich, and ME Cook. 2017. Adenine-induced hyperphosphatemia in a murine model of renal insufficiency. Nephrol Renal Dis. 2(3). doi: <a href="http://dx.doi.org/10.15761/NRD.1000126" target="_blank">10.15761/NRD.1000126</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/ans_pubs/377/
dc.identifier.articleid 1376
dc.identifier.contextkey 11719297
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath ans_pubs/377
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/9799
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/ans_pubs/377/2017_Bobeck_AdenineInduced.pdf|||Fri Jan 14 23:51:06 UTC 2022
dc.source.uri 10.15761/NRD.1000126
dc.subject.disciplines Animal Diseases
dc.subject.disciplines Animal Sciences
dc.subject.disciplines Statistical Models
dc.subject.keywords hyperphosphatemia
dc.subject.keywords renal insufficiency
dc.subject.keywords chronic kidney disease
dc.subject.keywords adenine
dc.title Adenine-induced hyperphosphatemia in a murine model of renal insufficiency
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 1914e5d6-c767-494e-8228-448fa7aa5672
relation.isOrgUnitOfPublication 85ecce08-311a-441b-9c4d-ee2a3569506f
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