BACKGROUND: Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD. METHODS: We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. RESULTS:Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m2 were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p=0.06 for all groups, p=0.65 for the 2 μg group) and for FMD (p=0.006 for all groups, p=0.54 for the 2 μg group). We found a borderline significance (p=0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. CONCLUSIONS:Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
RCT Entities:
BACKGROUND:Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabeticpatients with moderate CKD. METHODS: We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. RESULTS: Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m2 were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p=0.06 for all groups, p=0.65 for the 2 μg group) and for FMD (p=0.006 for all groups, p=0.54 for the 2 μg group). We found a borderline significance (p=0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. CONCLUSIONS: Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
Authors: Charlotte A Keyzer; G Fenna van Breda; Marc G Vervloet; Maarten A de Jong; Gozewijn D Laverman; Marc H Hemmelder; Wilbert M T Janssen; Hiddo J Lambers Heerspink; Arjan J Kwakernaak; Stephan J L Bakker; Gerjan Navis; Martin H de Borst Journal: J Am Soc Nephrol Date: 2016-11-17 Impact factor: 10.121
Authors: Kristen L Nowak; Michel Chonchol; Talat Alp Ikizler; Heather Farmer-Bailey; Natjalie Salas; Rafia Chaudhry; Wei Wang; Gerard Smits; Isak Tengesdal; Charles A Dinarello; Adriana M Hung Journal: J Am Soc Nephrol Date: 2016-09-19 Impact factor: 10.121
Authors: Nicholas Obermüller; Alexander R Rosenkranz; Hans-Walter Müller; Dennis Hidde; András Veres; Sabine Decker-Burgard; Isolde Weisz; Helmut Geiger Journal: Int J Mol Sci Date: 2017-09-28 Impact factor: 5.923
Authors: Josep M Cruzado; Ricardo Lauzurica; Julio Pascual; Roberto Marcen; Francesc Moreso; Alex Gutierrez-Dalmau; Amado Andrés; Domingo Hernández; Armando Torres; Maria Isabel Beneyto; Edoardo Melilli; Anna Manonelles; Manuel Arias; Manuel Praga Journal: Kidney Int Rep Date: 2017-09-28