Cinacalcet for Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Cinacalcet could decrease serum calcium, phosphate, and parathyroid hormone (PTH) in previous meta-analyses. However, the effect of cinacalcet on the new biomarkers such as fibroblast growth factor-23 (FGF-23), bone markers, and vascular calcification are still unestablished. We conducted a meta-analysis to examine the effects of cinacalcet on all laboratory and clinical spectrums of chronic kidney disease-mineral bone disorders (CKD-MBD). Methods: A systematic literature search was conducted in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov to identify randomized controlled trials (RCTs) comparing the effect of cinacalcet relative to standard treatment on CKD-MBD surrogate markers and clinical outcomes. Random-effect models were used to compute the weighted mean difference for continuous variables and the risk ratio for binary variables. Results: Twenty-four RCTs (10,031 dialysis patients) were identified. Besides lowering effects on calcium, phosphate, and PTH, cinacalcet significantly reduced bone resorptive marker (tartrate-resistant acid phosphatase 5b) but unaltered bone formation markers (bone alkaline phosphatase and osteocalcin). Cinacalcet also resulted in significant higher risk of hypocalcemia, nausea, vomiting, and diarrhea. Cinacalcet significantly lowered serum FGF-23 level, although unaltered all-cause mortalities. Conclusions: Use of cinacalcet in dialysis patients improves several CKD-MBD-related surrogate markers. However, the benefit on all-cause mortalities was not demonstrated.

The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism

“…Serum FGF-23 is associated with left ventricular hypertrophy and has been linked to an increased risk for cardiovascular mortality [2,3,32]. Although a recent meta-analysis demonstrated that cinacalcet can decrease serum FGF-23, most included studies were performed in nonsevere SHPT (serum iPTH levels below 1000 pg/mL) [13]. The present study illustrated that cinacalcet can still reduce serum FGF-23 in chronic HD patients with the median serum iPTH levels of around 1400 pg/mL (Table 1).…”

Secondary and Tertiary Hyperparathyroidism: A Narrative Review

“…Initial studies showed that treatment with cinacalcet is associated with a decrease of serum PTH, calcium, and phosphate levels, although moderately (30). A meta-analysis including over ten thousand ESRD patients found that cinacalcet significantly reduces PTH concentrations (weighted mean difference −22 pmol/L), calcium levels (weighted mean difference −0.7 mmol/L), and phosphate levels (weighted mean difference of −0.4 mmol/L) (31). Circulating FGF-23 levels also decrease significantly with cinacalcet treatment compared to vitamin D therapy alone (median change −40% (−63% to 16%), p < 0.001) (32).…”

Efficacy and safety of cinacalcet and active vitamin D in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease: a network meta-analysis

“…Cinacalcet and vitamin D as monotherapies or in combination are common treatments for SHPT in patients with CKD, aimed at achieving clinically acceptable levels of PTH and maintaining control of calcium and phosphorus levels. Numerous trials have documented the efficacy of these three regimens for the treatment of SHPT (20,30,(37)(38)(39)(40). However, there are currently two challenging questions facing the medical community with regard to these treatments.…”