Cinacalcet Shows Little Benefit in End-Stage Kidney Disease

Joe Barber Jr, PhD

May 07, 2013

Cinacalcet therapy does not appear to reduce all-cause or cardiovascular mortality among patients with chronic kidney disease (CKD) despite its ability to prevent parathyroidectomy in a few patients, according to the findings of a systemic review and meta-analysis.

Suetonia C. Palmer, MBChB, PhD, from the University of Otago Christchurch in New Zealand, and colleagues present their findings in an article published online April 30 in PLoS Medicine.

"People with [CKD] experience mortality in excess of the general population largely because of accelerated cardiovascular disease," the authors write. "Despite intensive efforts, numerous interventions to improve clinical outcomes in adults with CKD have failed to demonstrate beneficial effects on mortality or cardiovascular events, particularly for people treated with dialysis."

In the current analysis, the authors searched the Cochrane Renal Group specialized register and Embase to identify studies that assessed the effects of calcimimetics on mortality and adverse events. They identified 18 studies (7446 patients) for the systemic review and 17 studies (7424 patients) for the meta-analysis.

Compared with the efficacy of placebo or no treatment, cinacalcet did not improve all-cause mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.89 - 1.05; high-quality evidence) or cardiovascular mortality (RR, 0.67; 95% CI, 0.16 - 2.87) in patients with CKD stage 5. Nor did the drug alter the risk for all-cause (RR, 0.29; 95% CI, 0.06 - 1.48; low-quality evidence) or cardiovascular (RR, 0.29; 95% CI, 0.06 - 1.48) mortality in patients with CKD stages 3 to 5.

However, the therapy did reduce the need for parathyroidectomy in patients with CKD stage 5D (RR, 0.49; 95% CI, 0.40 - 0.59).

In the meta-analysis, cinacalcet therapy was associated with increased risks for hypocalcemia (RR, 7.38; 95% CI, 5.43 - 10.03; P < .001), nausea (RR, 2.05; 95% CI, 1.54 - 2.75; P < .001), vomiting (RR, 1.95; 95% CI, 1.74 - 2.18), and diarrhea (RR, 1.15; 95% CI, 1.02 - 1.29). In contrast, the drug was associated with a reduction in risk of hypercalcemia (RR, 0.23; 95% CI, 0.05 - 0.97).

The limitations of the study included insufficient data on treatment efficacy according to disease severity and a lack of data on patients receiving peritoneal dialysis.

"On average, treating 1,000 people with CKD stage 5D for 1 [year] had no effect on survival and prevented about three patients from experiencing parathyroidectomy, whilst 60 experienced hypocalcemia and 150 experienced nausea," the authors write.

Germaine Wong, MBBS, MMED, PhD, FRACP, from the University of Sydney in Australia, agreed that the findings failed to identify a mortality benefit for calcimimetic therapy. "Calcimimetics have been supported as an important strategy to reduce parathyroid hormone levels in people with CKD, with the belief that this would result in significant reduction in the risk of associated all-cause and cardiovascular mortality," Dr. Wong told Medscape Medical News by email. "Calcimimetics reduce parathyroid hormone levels, but not all-cause mortality, [and] hence should not be promoted as a strategy to improve survival in CKD."

One coauthor receives funding from Amgen. One coauthor received honoraria from Amgen and Abbott in addition to serving as a board member of the European Renal Best Practices Board. The remaining authors and commentator have disclosed no relevant financial relationships.

PLoS Med. Published online April 30, 2013. Full text