{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T10:33:38Z","timestamp":1781260418029,"version":"3.54.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fonds voor Wetenschappelijk Onderzoek Vlaanderen","award":["12B5916N"],"award-info":[{"award-number":["12B5916N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease\u2013mineral and bone disorder (CKD-MBD) rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To induce stable renal failure, rats were administered a 0.25% adenine diet for 8\u2009weeks. Concomitantly, rats were treated with vehicle, 2.5\u2009g\/kg\/day PA21, 5.0\u2009g\/kg\/day PA21 or 3.0\u2009g\/kg\/day calcium carbonate (CaCO3). Renal function and calcium\/phosphorus\/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rats treated with 2.5 or 5.0\u2009g\/kg\/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8\u2009weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfaa080","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T20:10:19Z","timestamp":1585167019000},"page":"1689-1699","source":"Crossref","is-referenced-by-count":15,"title":["Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure"],"prefix":"10.1093","volume":"35","author":[{"given":"Ellen","family":"Neven","sequence":"first","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00eblle","family":"Corremans","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A","family":"Vervaet","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Funk","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Vifor (International) Ltd, Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Walpen","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Vifor (International) Ltd, Glattbrugg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-433X","authenticated-orcid":false,"given":"Geert J","family":"Behets","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C","family":"D\u2019Haese","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-443X","authenticated-orcid":false,"given":"Anja","family":"Verhulst","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,10]]},"reference":[{"key":"2020100618543840000_gfaa080-B1","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1046\/j.1523-1755.1999.055Suppl.69018.x","article-title":"Iron deficiency in patients with renal failure","volume":"55(Suppl 69","author":"Nissenson","year":"1999","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B2","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1097\/01.ASN.0000133041.27682.A2","article-title":"Mineral metabolism, mortality, and morbidity in maintenance hemodialysis","volume":"15","author":"Block","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"2020100618543840000_gfaa080-B3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1053\/ajkd.1998.v31.pm9531176","article-title":"Association of serum phosphorus and calcium\u00d7phosphate product with mortality risk in chronic hemodialysis patients: a national study","volume":"31","author":"Block","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"2020100618543840000_gfaa080-B4","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1681\/ASN.V12102131","article-title":"Association of elevated serum PO(4), Ca\u00d7PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients","volume":"12","author":"Ganesh","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"2020100618543840000_gfaa080-B5","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1681\/ASN.2008060609","article-title":"Phosphorus binders and survival on hemodialysis","volume":"20","author":"Isakova","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"2020100618543840000_gfaa080-B6","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/ki.2013.185","article-title":"Use of phosphate-binding agents is associated with a lower risk of mortality","volume":"84","author":"Cannata-Andia","year":"2013","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B7","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1046\/j.1523-1755.2003.00284.x","article-title":"Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia","volume":"64","author":"Cozzolino","year":"2003","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B8","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/sj.ki.5002518","article-title":"The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer","volume":"72","author":"Russo","year":"2007","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1046\/j.1523-1755.2002.00434.x","article-title":"Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients","volume":"62","author":"Chertow","year":"2002","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B10","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/ndt\/gfh894","article-title":"Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density","volume":"20","author":"Asmus","year":"2005","journal-title":"Nephrol Dial Transplant"},{"key":"2020100618543840000_gfaa080-B11","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1111\/j.1523-1755.2005.00600.x","article-title":"Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis","volume":"68","author":"Block","year":"2005","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B12","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/sj.ki.5002059","article-title":"Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients","volume":"71","author":"Block","year":"2007","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B13","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1053\/j.ajkd.2013.03.023","article-title":"Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial","volume":"62","author":"Di Iorio","year":"2013","journal-title":"Am J Kidney Dis"},{"key":"2020100618543840000_gfaa080-B14","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/ki.2014.58","article-title":"A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients","volume":"86","author":"Floege","year":"2014","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B15","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/ndt\/gfv006","volume":"30","author":"Floege","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"2020100618543840000_gfaa080-B16","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1002\/jbmr.2585","article-title":"Disturbances in bone largely predict aortic calcification in an alternative rat model developed to study both vascular and bone pathology in chronic kidney disease","volume":"30","author":"Neven","year":"2015","journal-title":"J Bone Miner Res"},{"key":"2020100618543840000_gfaa080-B17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1124\/jpet.113.204792","article-title":"PA21, a new iron-based noncalcium phosphate binder, prevents vascular calcification in chronic renal failure rats","volume":"346","author":"Phan","year":"2013","journal-title":"J Pharmacol Exp Ther"},{"key":"2020100618543840000_gfaa080-B18","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1039\/an9891400143","article-title":"Direct determination of iron in urine and serum using graphite furnace atomic absorption spectrometry","volume":"114","author":"Liang","year":"1989","journal-title":"Analyst"},{"key":"2020100618543840000_gfaa080-B19","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s40620-017-0424-8","article-title":"Update on the role of bone biopsy in the management of patients with CKD-MBD","volume":"30","author":"Evenepoel","year":"2017","journal-title":"J Nephrol"},{"key":"2020100618543840000_gfaa080-B20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jbmr.1805","article-title":"Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee","volume":"28","author":"Dempster","year":"2013","journal-title":"J Bone Miner Res"},{"key":"2020100618543840000_gfaa080-B21","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"2020100618543840000_gfaa080-B22","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/s41598-018-38389-3","article-title":"Phosphate binding by sucroferric oxyhydroxide ameliorates renal injury in the remnant kidney model","volume":"9","author":"Nemoto","year":"2019","journal-title":"Sci Rep"},{"key":"2020100618543840000_gfaa080-B23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1124\/jpet.118.249961","article-title":"Phosphate binder, ferric citrate, attenuates anemia, renal dysfunction, oxidative stress, inflammation, and fibrosis in 5\/6 nephrectomized CKD rats","volume":"367","author":"Jing","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"2020100618543840000_gfaa080-B24","first-page":"98","article-title":"Ferric citrate attenuates cardiac hypertrophy and fibrosis in a rat model of chronic kidney disease","volume":"13","author":"Goto","year":"2019","journal-title":"Iran J Kidney Dis"},{"key":"2020100618543840000_gfaa080-B25","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1124\/jpet.118.251389","article-title":"The phosphate binder ferric citrate alters the gut microbiome in rats with chronic kidney disease","volume":"367","author":"Lau","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"2020100618543840000_gfaa080-B26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fendo.2018.00189","article-title":"FGF23 actions on target tissues\u2014with and without Klotho","volume":"9","author":"Richter","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2020100618543840000_gfaa080-B27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.biocel.2017.09.009","article-title":"FGF23 activates injury-primed renal fibroblasts via FGFR4-dependent signalling and enhancement of TGF-\u03b2 autoinduction","volume":"92","author":"Smith","year":"2017","journal-title":"Int J Biochem Cell Biol"},{"key":"2020100618543840000_gfaa080-B28","first-page":"174","article-title":"FGF23 promotes renal interstitial fibrosis by activating \u03b2-catenin","volume":"22","author":"Zhu","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2020100618543840000_gfaa080-B29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/s13104-018-3483-6","article-title":"Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients","volume":"11","author":"Shima","year":"2018","journal-title":"BMC Res Notes"},{"key":"2020100618543840000_gfaa080-B30","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1159\/000489964","article-title":"Ferric citrate decreases fibroblast growth factor 23 and improves erythropoietin responsiveness in hemodialysis patients","volume":"47","author":"Maruyama","year":"2018","journal-title":"Am J Nephrol"},{"key":"2020100618543840000_gfaa080-B31","doi-asserted-by":"crossref","first-page":"515606","DOI":"10.1155\/2015\/515606","article-title":"Effects of sucroferric oxyhydroxide compared to lanthanum carbonate and sevelamer carbonate on phosphate homeostasis and vascular calcifications in a rat model of chronic kidney failure","volume":"2015","author":"Phan","year":"2015","journal-title":"Biomed Res Int"},{"key":"2020100618543840000_gfaa080-B32","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1681\/ASN.2016121350","article-title":"C-terminal fibroblast growth factor 23, iron deficiency, and mortality in renal transplant recipients","volume":"28","author":"Eisenga","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2020100618543840000_gfaa080-B33","first-page":"1163","article-title":"Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients","volume-title":"Nephrol Dial Transplant","author":"Ketteler","year":"2019"},{"key":"2020100618543840000_gfaa080-B34","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.1096\/fj.201700667R","article-title":"Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia","volume":"32","author":"Agoro","year":"2018","journal-title":"FASEB J"},{"key":"2020100618543840000_gfaa080-B35","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2174\/1389200216666150206124424","article-title":"Preclinical pharmacokinetics, pharmacodynamics and safety of sucroferric oxyhydroxide","volume":"15","author":"Cozzolino","year":"2015","journal-title":"Curr Drug Metab"},{"key":"2020100618543840000_gfaa080-B36","first-page":"1330","article-title":"Iron-related parameters in dialysis patients treated with sucroferric oxyhydroxide","volume":"32","author":"Covic","year":"2017","journal-title":"Nephrol Dial Transplant"},{"key":"2020100618543840000_gfaa080-B37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bone.2016.11.012","article-title":"Vascular calcification in CKD-MBD: roles for phosphate, FGF23, and Klotho","volume":"100","author":"Yamada","year":"2017","journal-title":"Bone"},{"key":"2020100618543840000_gfaa080-B38","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/ki.2013.332","article-title":"Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency","volume":"85","author":"Jimbo","year":"2014","journal-title":"Kidney Int"},{"key":"2020100618543840000_gfaa080-B39","doi-asserted-by":"crossref","first-page":"e0180430","DOI":"10.1371\/journal.pone.0180430","article-title":"PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure","volume":"12","author":"Yaguchi","year":"2017","journal-title":"PLoS One"},{"key":"2020100618543840000_gfaa080-B40","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis","volume":"359","author":"Gutierrez","year":"2008","journal-title":"N Engl J Med"},{"key":"2020100618543840000_gfaa080-B41","doi-asserted-by":"crossref","first-page":"381082","DOI":"10.1155\/2014\/381082","article-title":"Cardiovascular risk factors and chronic kidney disease\u2014FGF23: a key molecule in the cardiovascular disease","volume":"2014","author":"Jimbo","year":"2014","journal-title":"Int J Hypertens"},{"key":"2020100618543840000_gfaa080-B42","doi-asserted-by":"crossref","first-page":"e0144119","DOI":"10.1371\/journal.pone.0144119","article-title":"Nonadherence to medication therapy in haemodialysis patients: a systematic review","volume":"10","author":"Ghimire","year":"2015","journal-title":"PLoS One"},{"key":"2020100618543840000_gfaa080-B43","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1681\/ASN.2018101058","article-title":"Effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor-23 in CKD: the COMBINE trial","volume":"30","author":"Ix","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"2020100618543840000_gfaa080-B44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/IJNRD.S182747","article-title":"Phosphate binder pill burden, adherence, and serum phosphorus control among hemodialysis patients converting to sucroferric oxyhydroxide","volume":"12","author":"Gray","year":"2019","journal-title":"Int J Nephrol Renovasc Dis"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/10\/1689\/33840227\/gfaa080.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/10\/1689\/33840227\/gfaa080.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T03:37:43Z","timestamp":1695958663000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/35\/10\/1689\/5869947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,10]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,7,10]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfaa080","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,7,10]]}}}