Peritoneal Delivery of Sodium Pyrophosphate Blocks

Authors: Rodrigo B de Oliveira Loïc Louvet Bruce L Riser Fellype C Barreto Joyce Benchitrit Raja Rezg Sabrina Poirot Vanda Jorgetti Tilman B Drüeke Ziad A Massy

Publish Date: 2015/06/19

Volume: 97, Issue: 2, Pages: 179-192

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Abstract

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 apolipoproteinE knockout mouse model with advanced VCs After CKD creation or sham surgery 12weekold female mice were randomized to one sham group and four CKD groups n = 18–19/group Treatment was initiated 8 weeks after left nephrectomy allowing prior VC development Uremic groups received either intraperitoneal PPi high dose 165 mg/kg or low dose 033 mg/kg per day oral sevelamer 3  in diet or placebo treatment for 8 weeks Both intima and media calcifications worsened with time in placebotreated CKD mice based on both quantitative image analysis and biochemical measurements Progression of calcification between 8 and 16 weeks 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 VCThe study was supported by a grant from Baxter We are grateful to Picardie Regional Council and Jules Verne University of Picardie for awarding postdoctoral grants to Fellype C Barreto and Rodrigo Bueno de Oliveira who also received a postdoctoral grant from CNPq Brazil The authors thank Charlotte Paquet Jules Verne University of Picardie for valuable technical help We also wish to thank Arpita Das Lianmei Feng Ahmed Fariyal and Paul Zieski Baxter Healthcare for the preparation of the peritoneal dialysis solutionsTilman B Drüeke declares having received honoraria as a consultant and/or speaker from Shire Genzyme and Amgen Ziad A Massy declares having received honoraria as speaker from FMC Genzyme and Amgen Vanda Jorgetti declares having received speaker honoraria consulting fees and/or research funding from Amgen Abbott and Genzyme At the time of the study Bruce L Riser was an employee of Baxter Healthcare a company with potential commercial interest in this research Other authors at Inserm Unit1088 UFR de Médicine/Pharmacie Amiens and the Division of Nephrology Amiens University Hospital and Jules Verne University of Picardy Amiens France have no competing interest

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