Cinacalcet Lowers Serum Alkaline Phosphatase in Maintenance Hemodialysis Patients

Abstract

Background and objectives: Studies suggest an association between elevated serum alkaline phosphatase (AP) and increased mortality in hemodialysis patients, but the effect of existing therapies on AP is not fully understood. We assessed the effects of cinacalcet on AP in a secondary analysis of controlled trial data.Design, setting, participants, & measurements: This was a post hoc analysis of data from three 26-wk randomized, double-blind, placebo-controlled, phase 3 trials and a 26-wk double-blind, placebo-controlled extension trial that investigated cinacalcet in secondary hyperparathyroidism treatment in dialysis patients. Hemodialysis patients (n ‫؍‬ 890) with intact parathyroid hormone >300 pg/ml and serum calcium >8.4 mg/dl received cinacalcet plus standard therapy or standard therapy alone for up to 52 wk. Total, not bone-specific, AP was assessed (proportion of cinacalcet/control subjects achieving a >20% or any AP reduction from baseline; the proportion of subjects with AP >120 U/L) at baseline; the end of titration; and study weeks 26, 42, and 52.Results: At 52 wk, a greater proportion of cinacalcet-treated patients had either a >20% (39 versus 18%) or any (58 versus 36%) AP reduction compared with control subjects, respectively. The likelihood of achieving either a >20% or any AP reduction (determined by relative proportion) was 2.33 (95% confidence interval 1.50 to 3.61) and 1.74 (95% confidence interval 1.31 to 2.31), respectively, at week 52. Cinacalcet treatment tended toward a decreased percentage of patients with AP >120 U/L (baseline, 42.6%; week 52, 30.6%) compared with control (35.0 to 48.6%, respectively).Conclusions: In this combined analysis of controlled trials of patients who were receiving hemodialysis, cinacalcet lowered total serum AP.

Comparative Mortality–Predictability Using Alkaline Phosphatase and Parathyroid Hormone in Patients on Peritoneal Dialysis and Hemodialysis

“…In contrast, our findings suggest that, when examined as a baseline measurement, elevated ALP is associated with increased mortality in PD patients, even within high-normal ranges. Given that several therapeutic interventions (activated vitamin D and calcimimetics, for example) have been shown to lower ALP concentrations, further study is needed to determine if a reduction in serum ALP leads to improved outcomes (46,47).…”

Association of Cumulatively Low or High Serum Calcium Levels with Mortality in Long-Term Hemodialysis Patients

“…For this study, data on oral medications including calcimimetics or phosphorus binders were not available. The calcimimetic cinacalcet became available in the United States during the last few months of this cohort [26,27]. Hence, the cohort is practically a precalcimimetic cohort.…”

Clinical Outcomes with Active versus Nutritional Vitamin D Compounds in Chronic Kidney Disease

“…Conversely, as shown in Table 4, the level of circulating AP can be effectively decreased by active vitamin D products (51,52,76 -78) (and possibly also calcimimetics [79], further description of which is beyond the scope of this focused review paper). Indeed a recent meta-analysis, which questioned the PTH lowering effect of active vitamin D analogs, showed that these agents can decrease serum AP effectively (80).…”