title: Paricalcitol and endothelial function in chronic kidney disease trial.
abstract: Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.). carmine.zoccali@tin.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curatola
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panuccio
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Rocco
authors.initials: R
authors.lastname: Tripepi
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pizzini
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Marica
authors.initials: M
authors.lastname: Versace
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Davide
authors.initials: D
authors.lastname: Bolignano
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cutrupi
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Raffaele
authors.initials: R
authors.lastname: Politi
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: From the Nephrology, Hypertension, and Renal Transplantation Unit, Ospedali Riuniti, Reggio Calabria, Italy (C.Z., V.P., F.M.); CNR-IBIM/IFC Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Calabria, Italy (C.Z., G.C., V.P., R.T., P.P., M.V., D.B., S.C., R.P., G.T., F.M.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (L.G.); and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston (R.T.).
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D004872:Ergocalciferols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D012720:Severity of Illness Index; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; C084656:paricalcitol; D002118:Calcium
keywords: atherosclerosis; chronic kidney disease; endothelium; hypertension; paricalcitol; vitamin D