Ckd-mbd-b mo

Introduction and Aims: Secondary hyperparathyroidism (HPT) is common in patients on maintenance hemodialysis and often progresses despite treatment with vitamin D sterols and phosphate binders. Methods: The EVOLVE trial randomized 3883 patients with moderate to severe secondary HPT with a median plasma intact parathyroid hormone (PTH) concentration of 693 pg/mL (normal range 11–72 pg/mL) to treatment with cinacalcet or placebo. The majority of patients also received vitamin D sterols and phosphate binders. Patients were followed for up to 64 months. We assessed the rates of parathyroidectomy (PTX), switching to commercial cinacalcet, and progress to severe unremitting HPT (defined as iPTH values >1000 pg/mL and serum total calcium >2.6 mmol/L on two consecutive occasions, or iPTH > 1000 pg/mL and serum total calcium >2.6 mmol/L on one occasion with prescription of commercial cinacalcet). Results: In the group randomized to placebo (n=1935) nearly 70% received vitamin D sterols and 90% phosphate binders throughout the trial. Nonetheless, 278 (14.4%) patients had surgical PTX, with a median (p10, p90) iPTH level of 1873 (760, 3706) pg/mL before surgery, 443 (22.9%) patients started commercial cinacalcet with a median iPTH of 1108 (455, 2310) pg/mL, and 470 (24.3%) progressed to severe unremitting HPT with a median PTH of 1510 (810, 2991) pg/mL. Substantial selection bias was evident in patients who either underwent PTX, were prescribed commercial cinacalcet, or progressed to severe unremitting HPT, with these outcomes differing widely by age, sex, region and comorbidity. The unadjusted relative hazard in the cinacalcet vs. placebo group for PTX was 0.44 (95% CI 0.36-0.54), for provision of commercial cinacalcet 0.41 (95% CI 0.35-0.48), and for progression to severe unremitting HPT with hypercalcemia 0.43 (95% CI 0.37-0.50). Conclusions: Severe unremitting HPT developed frequently in patients randomized to placebo in EVOLVE, despite the use of conventional therapy with vitamin D sterols and phosphate binders, prompting PTX or motivating the off-protocol use of commercial cinacalcet. Randomization to cinacalcet resulted in a nominally significant reduction in the occurrence of these events.