Study Finds Better Survival With Cinacalcet Than Parathyroidectomy in CKD

Cinacalcet beats parathyroidectomy for improving survival of patients on chronic hemodialysis. The use of a vitamin D receptor activator (VDRA) along with cinacalcet produced additional survival benefit, researchers reported at the European Renal Association—European Dialysis and Transplant Association conference in Amsterdam in June.

These findings, from the 3-year, open-cohort, prospective Current management Of Secondary hyperparathyroidism –– a Multicenter Observational Study (COSMOS), suggest that further, randomized, controlled trials should be conducted comparing medical vs. surgical treatment in the management of secondary hyperparathyroidism in chronic kidney disease (CKD).

It has been estimated that during the course of severe renal insufficiency more than 90 precent of patients on dialysis will develop some degree of secondary hyperparathyroidism. Increased serum parathyroid hormone (PTH) levels can lead to osteodystrophy, with attendant bone pain and fracture risk. In addition, vascular calcification can lead to cardiovascular events and death.

Parathyroidectomy can lower PTH levels. Alternatively, administration of active vitamin D can also normalize PTH levels, but serum calcium and phosphorus levels may increase significantly, again leading to vascular calcification. Cinacalcet (Sensipar, Amgen), by increasing the sensitivity of the calcium-sensing receptors in the parathyroid glands, inhibits excess production of PTH. Still, the question remained whether lowering serum PTH levels in itself was sufficient, or if the specific intervention that lowered the levels was important.

COSMOS gathered data from 227 hemodialysis centers in 20 European countries to evaluate methods of managing mineral and bone disorders in CKD. The study, conducted by Jorge Cannata-Andia, MD, head of the Bone and Mineral Research Unit at the Central University Hospital of Asturias and the University of Oviedo, Spain, and colleagues included 6251 hemodialysis patients—4285 at baseline and 1966 to replace those who died, received kidney transplants, switched to peritoneal dialysis, or were lost to follow-up.

The researchers used several approaches to analyzing the data, depending on whether patients were exposed to parathyroidectomy or to cinacalcet or not, with similar findings.

They found that cinacalcet use (independent of VDRAs) was associated with a 26 percent reduction in mortality risk (hazard ratio, 0.74). Combining cinacalcet with VDRAs lowered the risk by an additional 10 percent (hazard ratio, 0.65). Parathyroidectomy was not associated with a reduction in the risk of death.

The researchers concluded that the use of cinacalcet was superior to parathyroidectomy in terms of reducing the risk of mortality. Additional benefits were seen when VDRAs were added to cinacalcet.

Because observational studies, such as COSMOS, are subject to bias and confounding, the researchers advised performing randomized, controlled trials comparing cinacalcet and parathyroidectomy in this patient population.