caa a22 4500 605521026 CHVBK 20210128100738.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00223-015-0020-7 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0020-7 Peritoneal Delivery of Sodium Pyrophosphate Blocks the Progression of Pre-existing Vascular Calcification in Uremic Apolipoprotein-E Knockout Mice [Elektronische Daten] [Rodrigo de Oliveira, Loïc Louvet, Bruce Riser, Fellype Barreto, Joyce Benchitrit, Raja Rezg, Sabrina Poirot, Vanda Jorgetti, Tilman Drüeke, Ziad Massy] Chronic kidney disease (CKD) is generally associated with disturbances of mineral and bone metabolism. They contribute to the development of vascular calcification (VC), a strong, independent predictor of cardiovascular risk. Pyrophosphate (PPi), an endogenous inhibitor of hydroxyapatite formation, has been shown to slow the progression of VC in uremic animals. Since in patients with CKD treatment is usually initiated for already existing calcifications, we aimed to compare the efficacy of PPi therapy with that of the phosphate binder sevelamer, using a uremic apolipoprotein-E knockout mouse model with advanced VCs. After CKD creation or sham surgery, 12-week-old female mice were randomized to one sham group and four CKD groups (n=18-19/group). Treatment was initiated 8weeks after left nephrectomy allowing prior VC development. Uremic groups received either intraperitoneal PPi (high dose, 1.65mg/kg or low dose, 0.33mg/kg per day), oral sevelamer (3% in diet), or placebo treatment for 8weeks. Both intima and media calcifications worsened with time in placebo-treated CKD mice, based on both quantitative image analysis and biochemical measurements. Progression of calcification between 8 and 16weeks was entirely halted by PPi treatment, as it was by sevelamer treatment. PPi did not induce consistent bone histomorphometry changes. Finally, the beneficial vascular action of PPi probably involved mechanisms different from that of sevelamer. Further studies are needed to gain more precise insight into underlying mechanisms and to see whether PPi administration may also be useful in patients with CKD and VC. Springer Science+Business Media New York, 2015 Apolipoprotein-E knockout mice nationallicence Chronic kidney disease nationallicence Mineral and bone disorder nationallicence Sevelamer hydrochloride nationallicence Sodium pyrophosphate nationallicence Vascular calcification nationallicence de Oliveira Rodrigo INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Louvet Loïc INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Riser Bruce BLR BIO, LLC, 313 54th Street, 53140, Kenosha, WI, USA aut Barreto Fellype INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Benchitrit Joyce INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Rezg Raja INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Poirot Sabrina INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Jorgetti Vanda Division of Nephrology, São Paulo University, Av. Dr. Arnaldo, 455, 3º andar, sala 3342, CEP 01246-903, São Paulo, SP, Brazil aut Drüeke Tilman INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Massy Ziad INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 179-192 0171-967X 97:2<179 2015 97 223 https://doi.org/10.1007/s00223-015-0020-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0020-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- de Oliveira Rodrigo INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Louvet Loïc INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Riser Bruce BLR BIO, LLC, 313 54th Street, 53140, Kenosha, WI, USA aut NATIONALLICENCE 700 1- Barreto Fellype INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Benchitrit Joyce INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Rezg Raja INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Poirot Sabrina INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Jorgetti Vanda Division of Nephrology, São Paulo University, Av. Dr. Arnaldo, 455, 3º andar, sala 3342, CEP 01246-903, São Paulo, SP, Brazil aut NATIONALLICENCE 700 1- Drüeke Tilman INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 700 1- Massy Ziad INSERM Unit 1088, UFR de Médecine et de Pharmacie, University of Picardie Jules Verne (UPJV), 1 rue des Louvels, 80037, Amiens, France aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/2(2015-08-01), 179-192 0171-967X 97:2<179 2015 97 223