Effects of Vitamin D receptor activation and dietary sodium restriction on residual albuminuria in CKD: The ViRTUE-CKD trial

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 sodiumrestriction on residual albuminuria in CKD. In amulticenter, 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 (2μmg/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 intentionto- treat analysis, albuminuria (geometric mean)was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS+PLACand 990 (95%confidence interval, 755 to 1299)mg/24 h during RS+PARI (P=0.20versusRS+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 of174±64mmolNa+ perday in the combinedRSgroups and108±61mmolNa+perdayintheLSgroups (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.