Dr. Stuart M. Sprague (SMS), from NorthShore University Health System University of Chicago Pritzker School of Medicine (Evanston, Illinois), discusses his abstracts for the National Kidney Foundation’s 2016 Spring Clinical Meetings (SCM16), FGF-23 and CKD-MBD Indices After 1 Year of Treatment With Sucroferric Oxyhydroxide in African American Dialysis Patients and 1-Year Efficacy and Safety of Sucroferric Oxyhydroxide in a Sub-Population of African American Dialysis Patients, with Dr. Kenar Jhaveri, AJKD Blog Editor.
AJKDblog: Why don’t you tell us a little about your research and abstract being presented at the NKF 2016 Spring Meetings?
SMS: The two abstracts being presented at the Spring Clinicals feature data from a large Phase 3 clinical study comparing the efficacy and safety of an iron-based phosphate binder, sucroferric oxyhydroxide (VELPHORO®), with sevelamer carbonate (Renvela®) in dialysis patients with hyperphosphatemia.
In the posters, we present the results of a sub-group analysis to evaluate the efficacy and safety of VELPHORO® in African American patients, who represented approximately 20% (202/1,041) of the overall study population. In the United States, the prevalence of CKD is greater in African Americans (15%) compared with other ethnic groups (~10%), and African Americans comprise approximately one-third of all dialysis patients. It is important, therefore, to investigate the clinical effects of new phosphate binder treatments in this patient population.
The results of our analyses demonstrated that sucroferric oxyhydroxide had similar efficacy to sevelamer carbonate in reducing serum phosphorus levels in African American patients; however, this phosphorus-lowering effect was achieved with a lower number of pills for sucroferric oxyhydroxide vs sevelamer carbonate (a mean of 3.4 tablets/day vs. 7.6 tablets/day, respectively). Furthermore, treatment with sucroferric oxyhydroxide and sevelamer carbonate was also associated with significant reductions in serum fibroblast growth factor-23 levels. Both phosphate binder treatments were well tolerated. In summary, the findings of our sub-group analyses on African American patients were consistent with what we observed in the overall Phase 3 study population.
AJKDblog: Are you concerned about the increasing calcium levels given that calcium concentration is the one of the quality measures for dialysis matrix?
SMS: We are extremely concerned about increasing serum calcium levels. Although, the role of serum calcium in patient outcomes has not been directly tested in prospective studies, reductions in serum calcium occurred in the outcome trials involving either calcium-free phosphate binders or calcimimetics in chronic kidney disease (CKD) and end-stage renal disease (ESRD). The decrease in serum calcium was associated with less progression of coronary artery calcification in the calcium-free phosphate binder groups in all but one study. The “ADVANCE” study utilizing cinacalcet in HD patients also demonstrated less vascular calcification with a lower serum calcium. The few studies that evaluated mortality or cardiovascular events in patients treated with either sevelamer or cinacalcet also showed a reduction in death or cardiovascular events in the treated patients that was accompanied by a decrease in serum calcium. Finally, I am concerned by what appears to be an increasing incidence of calciphylaxis, or calcific uremic arteriopathy, in our dialysis population. Although, hyperphosphatemia plays a major role in the pathophysiology, the use of calcium-containing phosphate binders clearly appears to be a risk factor. Thus, I believe the data fully supports the quality matrix that we should strive to achieve low normal serum calcium concentrations and avoid the use of agents that increase serum calcium levels.
AJKDblog: Where do you and your group go from here?
SMS: It is clear that disorders in mineral metabolism, especially hyperphosphatemia, are a major cause of morbidity and mortality in both CKD and ESRD patients. Current regimens of phosphate binders, though somewhat effective in lowering serum phosphate, have failed to adequately control phosphate in the majority of patients. This is due in part to the large pill burden and risk of increasing serum calcium. It is clear that VELPHORO® can control phosphate at least as well as the other binders, but with a significantly lower pill burden. Our future studies should focus on obtaining adequate phosphate control in the majority of patients, addressing the higher risk patient groups (e.g., African Americans), determining methods to increase compliance, and finally demonstrating improved outcomes in both CKD and ESRD.
All Spring Clinical Meeting abstracts are available in the May issue of AJKD.