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We hypothesized that the accumulation of advanced glycation end-products (AGEs) in CKD may be responsible for the vascular and bone pathologies via alteration of collagen. We treated a naturally occurring model of CKD-MBD, the Cy\/+ rat, with a normal and high dose of the AGE crosslink breaker alagebrium (ALT-711), or with calcium in the drinking water to mimic calcium phosphate binders for 10\u2009weeks. These animals were compared to normal (NL) untreated animals. The results showed that CKD animals, compared to normal animals, had elevated blood urea nitrogen (BUN), PTH, FGF23 and phosphorus. Treatment with ALT-711 had no effect on kidney function or PTH, but 3\u2009mg\/kg lowered FGF23 whereas calcium lowered PTH. Vascular calcification of the aorta assessed biochemically was increased in CKD animals compared to NL, and decreased by the normal, but not high dose of ALT-711, with parallel decreases in left ventricular hypertrophy. ALT-711 (3\u2009mg\/kg) did not alter aorta AGE content, but reduced aorta expression of receptor for advanced glycation end products (RAGE) and NADPH oxidase 2 (NOX2), suggesting effects related to decreased oxidative stress at the cellular level. The elevated total bone AGE was decreased by 3\u2009mg\/kg ALT-711 and both bone AGE and cortical porosity were decreased by calcium treatment, but only calcium improved bone properties. In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD. \u00a9 2019 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.3925","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T21:43:21Z","timestamp":1574199801000},"page":"608-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Effect of Advanced Glycation End-Products (AGE) Lowering Drug ALT-711 on Biochemical, Vascular, and Bone Parameters in a Rat Model of CKD-MBD"],"prefix":"10.1093","volume":"35","author":[{"given":"Neal X","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruthi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalisha","family":"O'Neill","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-1896","authenticated-orcid":false,"given":"Thomas L","family":"Nickolas","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Columbia University Medical Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-8058","authenticated-orcid":false,"given":"Joseph M","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Indiana University-Purdue University at Indianapolis Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University School of Medicine Indianapolis IN USA"},{"name":"Division of Nephrology, Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne E","family":"Metzger","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Creecy","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Indiana University-Purdue University at Indianapolis 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