title: Paricalcitol for secondary hyperparathyroidism in renal transplantation.
abstract: Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Matias
authors.initials: M
authors.lastname: Trillini
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Monica
authors.initials: M
authors.lastname: Cortinovis
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Jorge
authors.initials: J
authors.lastname: Reyes Loaeza
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Karen
authors.initials: K
authors.lastname: Courville
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ferrer-Siles
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Prandini
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cannata
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Villa
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.affiliation: Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Gotti
authors.affiliation: Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Caruso
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Davide
authors.initials: D
authors.lastname: Martinetti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and Unit of Nephrology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy giuseppe.remuzzi@marionegri.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases "Aldo & Cele Daccò," Bergamo, Italy; and.
authors.forename: Norberto
authors.initials: N
authors.lastname: Perico
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D004872:Ergocalciferols / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D011183:Postoperative Complications / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy; D014807:Vitamin D / Q000097:blood
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; C084656:paricalcitol; D003404:Creatinine; D002118:Calcium
keywords: hyperparathyroidism; kidney transplantation; proteinuria; vitamin D