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 (2 μg/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: 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, Holland Nephrology Study (HONEST) Network
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 28 Issue 4 Pg. 1296-1305 (Apr 2017) ISSN: 1533-3450 [Electronic] United States
• PMID: 27856633 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2017 by the American Society of Nephrology.

Chemical References

• Ergocalciferols
• Receptors, Calcitriol
• paricalcitol

Topics

• Albuminuria (etiology, therapy)
• Combined Modality Therapy
• Cross-Over Studies
• Diet, Sodium-Restricted
• Double-Blind Method
• Ergocalciferols (therapeutic use)
• Humans
• Receptors, Calcitriol (physiology)
• Renal Insufficiency, Chronic (complications)