title: Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial.
abstract: Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+per day in the combined RS groups and 108±61 mmol Na+per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Keyzer
authors.affiliation: Department of Nephrology and Institute for Cardiovascular Research, Vrije University Medical Centre, Amsterdam, The Netherlands.
authors.forename: G Fenna
authors.initials: GF
authors.lastname: van Breda
authors.affiliation: Department of Nephrology and Institute for Cardiovascular Research, Vrije University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Maarten A
authors.initials: MA
authors.lastname: de Jong
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Zorggroep Twente Hospital, Almelo, The Netherlands.
authors.forename: Gozewijn D
authors.initials: GD
authors.lastname: Laverman
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands; and.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Hemmelder
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Martini Hospital Groningen, Groningen, The Netherlands.
authors.forename: Wilbert M T
authors.initials: WM
authors.lastname: Janssen
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Kwakernaak
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Internal Medicine, Division of Nephrology and m.h.de.borst@umcg.nl.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000628:therapy*; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D004039:Diet, Sodium-Restricted; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000627:therapeutic use*; D006801:Humans; D018167:Receptors, Calcitriol / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000150:complications*
chemical_list: D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol
keywords: VDRA; albuminuria; chronic kidney disease; dietary sodium restriction; paricalcitol; randomized-controlled trial