Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial

• Published in: Journal of the American Society of Nephrology Vol. 28; no. 4; pp. 1296 - 1305
• Main Authors: Keyzer, Charlotte A., van Breda, G. Fenna, Vervloet, Marc G., de Jong, Maarten A., Laverman, Gozewijn D., Hemmelder, Marc H., Janssen, Wilbert M.T., Lambers Heerspink, Hiddo J., Kwakernaak, Arjan J., Bakker, Stephan J.L., Navis, Gerjan, de Borst, Martin H.
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.04.2017
• Subjects: Albuminuria - etiology; Albuminuria - therapy; Clinical Research; Combined Modality Therapy; Cross-Over Studies; Diet, Sodium-Restricted; Double-Blind Method; Ergocalciferols - therapeutic use; Humans; Receptors, Calcitriol - physiology; Renal Insufficiency, Chronic - complications; randomized-controlled trial; albuminuria; chronic kidney disease; paricalcitol; VDRA; dietary sodium restriction
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2016040407

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 μ g/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.