Paricalcitol, Microvascular and Endothelial Function in Non-Diabetic Chronic Kidney Disease: A Randomized Trial.
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).
Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden.
Kristina
K
Lundwall
Gun
G
Jörneskog
Stefan H
SH
Jacobson
Jonas
J
Spaak
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001916:Brachial Artery / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004872:Ergocalciferols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D020678:Microscopic Angioscopy; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D063177:Pulse Wave Analysis; D018167:Receptors, Calcitriol / Q000819:agonists*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D016896:Treatment Outcome; D014463:Ultrasonography; D059289:Vascular Stiffness / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol