Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients

Abstract

Background: Calcimimetic agents lower abnormal serum parathyroid hormone (PTH) levels in people who have chronic kidney disease (CKD), but the benefits and harms on patient-level outcomes are uncertain. Since this review was first published in 2006 showing that evidence for calcimimetics was largely restricted to biochemical outcomes, additional studies have been conducted. This is an update of a review first published in 2006. Objectives: To evaluate the benefits and harms of cinacalcet on patient-level outcomes in adults with CKD. Search methods: MEDLINE, EMBASE, CENTRAL and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in adults with CKD (persistent albuminuria > 30 mg/g with or without reduced glomerular filtration rate (GFR) (below 60 mL/min/1.73 m2)). We updated searches to 7 February 2013 including the Cochrane Renal Group's Specialised Register to complete this update. Selection criteria: We included all RCTs of a calcimimetic administered to patients with CKD for the treatment of elevated serum PTH levels. Data collection and analysis: Data were extracted on all relevant patient-centred and surrogate outcomes. We summarised treatment estimates using random effects and expressed treatment effects as a risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results: Eighteen studies (7446 participants) compared cinacalcet in addition to standard therapy with no treatment or placebo plus standard therapy. In adults with GFR category G5 (GFR below 15 mL/min/1.73 m2) treated with dialysis, routine cinacalcet treatment had little or no effect on all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05), imprecise effects on cardiovascular mortality (RR 0.67, 95% CI 0.16 to 2.87), and prevented surgical parathyroidectomy (RR 0.49, 95% CI 0.40 to 0.59) and hypercalcaemia (RR 0.23, 95% CI 0.05 to 0.97), but increased hypocalcaemia (RR 6.98, 95% CI 5.10 to 9.53), nausea (RR 2.02, 95% CI 1.45 to 2.81) and vomiting (RR 1.97, 95% CI 95% CI 1.73 to 2.24). Cinacalcet decreased serum PTH (MD -281.39 pg/mL, 95% CI -325.84 to -234.94) and calcium (MD -0.87 mg/dL, 95% CI -0.96 to -0.77) levels, but had little or no effect on serum phosphorous levels (MD -0.23 mg/dL, 95% CI -0.58 to 0.12). Data were sparse for adults with GFR categories G3a to G4 (GFR 15 to 60 mL/min/1.73 m2) and kidney transplant recipients. Overall, based on GRADE criteria, evidence for cinacalcet in adults with GFR category G5 treated with dialysis (mortality, parathyroidectomy, hypocalcaemia, and nausea) is of high or moderate quality. High quality evidence suggests "further research is very unlikely to change our confidence in the estimate of treatment effect" and moderate quality evidence is "further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate". Information for adults with less severe CKD GFR category G3a to G4 is of low or very low quality. This means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Authors' conclusions: Routine cinacalcet therapy reduced the need for parathyroidectomy in adults treated with dialysis and elevated PTH levels but does not improve all-cause or cardiovascular mortality. Cinacalcet increases risks of nausea, vomiting and hypocalcaemia, suggesting harms may outweigh benefits in this population.