Cinacalcet but not vitamin D use modulates the survival benefit associated with sevelamer in the INDEPENDENT study

Whether differences in outcomes of calcium-free vs. calcium-containing phosphate binder treatments can be amplified by concurrent treatment with a calcium-sensing receptor agonist or vitamin D remains to be elucidated.

A post-hoc analysis of the INDEPENDENT study, an open-label randomized controlled trial designed to evaluate the impact of sevelamer (SV) vs. calcium salts (CS) on survival in incident dialysis patients.

We recruited 466 middle-aged men and women. Cinacalcet (CC) and vitamin D (VD) were administered to a portion of patients as part of their routine care. We tested the impact of CC and VD on survival in the overall and in both treatment arms of the original study cohort. Overall SV, but not CC or VD, administration was associated with a survival benefit (mean follow-up: 28 (10) months). However, a significant (p = 0.006) interaction of SV and CC on mortality was observed. CC use was associated with improved survival if administered in combination with SV (HR 0.34, 95% CI 0.14 - 0.81, p = 0.01 for subjects receiving or not CC) but not CS (HR 1.28, 95% CI 0.82 - 2.00; p = 0.26 for subjects receiving or not CC). No effect on mortality or interaction of phosphate binder use with VD was noted.

Though hypothesis generating, these results lend support to the idea that use of a CC may increase survival in incident hemodialysis patients when used with a calcium-free phosphate binder.