title: Protective Effects of Paricalcitol on Peritoneal Remodeling during Peritoneal Dialysis.
abstract: Peritoneal dialysis (PD) is associated with structural and functional alterations of the peritoneal membrane, consisting of fibrosis, angiogenesis, and loss of ultrafiltration capacity. Vitamin D receptor activation (VDRA) plays an important role in mineral metabolism and inflammation, but also antiangiogenic and antifibrotic properties have been reported. Therefore, the effects of active vitamin D treatment on peritoneal function and remodeling were investigated. Rats were either kept naïve to PDF exposure or daily exposed to 10 mL PDF and were treated for five or seven weeks with oral paricalcitol or vehicle control. Non-PDF-exposed rats showed no peritoneal changes upon paricalcitol treatment. Paricalcitol reduced endogenous calcitriol but did not affect mineral homeostasis. However, upon PDF exposure, loss of ultrafiltration capacity ensued which was fully rescued by paricalcitol treatment. Furthermore, PD-induced ECM thickening was significantly reduced and omental PD-induced angiogenesis was less pronounced upon paricalcitol treatment. No effect of paricalcitol treatment on total amount of peritoneal cells, peritoneal leukocyte composition, and epithelial to mesenchymal transition (EMT) was observed. Our data indicates that oral VDRA reduces tissue remodeling during chronic experimental PD and prevents loss of ultrafiltration capacity. Therefore, VDRA is potentially relevant in the prevention of treatment technique failure in PD patients.
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Andrea W D
authors.initials: AW
authors.lastname: Stavenuiter
authors.affiliation: Department of Nephrology, VU University Medical Center, 1007 MB Amsterdam, Netherlands.
authors.forename: Karima
authors.initials: K
authors.lastname: Farhat
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Vila Cuenca
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Margot N
authors.initials: MN
authors.lastname: Schilte
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Eelco D
authors.initials: ED
authors.lastname: Keuning
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Nanne J
authors.initials: NJ
authors.lastname: Paauw
authors.affiliation: Department of Nephrology, VU University Medical Center, 1007 MB Amsterdam, Netherlands.
authors.forename: Pieter M
authors.initials: PM
authors.lastname: ter Wee
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands.
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Beelen
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands ; Department of Nephrology, VU University Medical Center, 1007 MB Amsterdam, Netherlands ; Institute for Cardiovascular Research VU (ICaR-VU), VU University Medical Center, 1007 MB Amsterdam, Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
mesh_terms: D000818:Animals; D004872:Ergocalciferols / Q000494:pharmacology*; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control*; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism*
chemical_list: D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol