title: Magnetic bead-based proteomic technology to study paricalcitol effect in kidney transplant recipients.
abstract: Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease and frequently persists after kidney transplantation. Paricalcitol, a selective vitamin D receptor activator, is indicated in the management of this disorder and recent evidences have suggested that this drug has other beneficial effects. Aiming to elucidate these effects, our study included 52 stable kidney transplant recipients randomized 2:1 to treatment with paricalcitol or to no treatment. Bone mineral parameters, kidney function and inflammatory status were assessed at baseline, at 3 and at 12 months. Moreover, a proteomic approach, based on magnetic beads technology coupled to MALDI-TOF mass spectrometry readout, was used to determine changes in patients' plasma peptidome. Patients treated with paricalcitol showed a significant decrease in parathyroid hormone and alkaline phosphatase levels, and an increase of bone mineral density and glomerular filtration rate. The proteomic analysis revealed a decrease in bradykinin after paricalcitol treatment, whereas 2 peptides identified as fragments of the complement factor C4 decreased only in those patients not treated with paricalcitol. These findings suggest that paricalcitol may offer additional benefits due to immunomodulatory effects via the kallikrein-kinin and complement systems.
authors.affiliation: Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet, 08916, Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pérez
authors.forename: Anna
authors.initials: A
authors.lastname: Sánchez-Escuredo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lauzurica
authors.forename: Beatriu
authors.initials: B
authors.lastname: Bayés
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro-Muñoz
authors.forename: María Cruz
authors.initials: MC
authors.lastname: Pastor
authors.forename: Laura
authors.initials: L
authors.lastname: Cañas
authors.forename: Josep
authors.initials: J
authors.lastname: Bonet
authors.forename: Ramón
authors.initials: R
authors.lastname: Romero
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D001920:Bradykinin / Q000097:blood / Q000737:chemistry; D003181:Complement C4 / Q000032:analysis / Q000737:chemistry; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D016030:Kidney Transplantation / Q000276:immunology; D060328:Magnetic Phenomena; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry; D040901:Proteomics / Q000379:methods; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D003181:Complement C4; D004872:Ergocalciferols; D010446:Peptide Fragments; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C084656:paricalcitol; D001920:Bradykinin