Patients
This was a randomized, prospective, open-label, parallel group study approved by both the Institutional Review Board (IRB) at the Albany College of Pharmacy and Health Sciences and the IRB at the Albany Medical Center. Fifty CKD (stages 3 and 4) patients were recruited from the Albany Medical Center South Campus facility between 2011 and 2015. Patients were included in the study if they were males or females ≥ 18 years of age at the start of screening, CKD stage 3 or 4 (eGFR 15-60 mL/min/1.73m2), not expected to start dialysis for 8 months, serum intact PTH < 500 pg/mL during the screening period, and a stable dose of ACEi/ARB regimen 30 days prior to screening. Over 80% of study subjects were Caucasian and male.
The duration of the study was 15 weeks in total spilt into 3 phases: screening phase, washout phase, and treatment phase (Figure 1). Written informed consent was obtained prior to any screening procedures. Study subjects’ laboratory data was screened to ensure they fulfilled the inclusion criteria. The following examinations and assessments were conducted one time during the 30-day screening period: demographics, medical history, iPTH, pregnancy test (if applicable), and medication history. Study subjects were randomized by a computer program in a 1:1 ratio to receive either sevelamer carbonate or calcium acetate. If applicable, phosphate binder therapy was discontinued in study subjects receiving phosphate binder therapy 3 weeks prior to starting study medications during the washout phase. Study subjects only took phosphate binder if they were randomized to during the treatment phase. Baseline characteristics of the study subjects are presented in Table 1.
Study subjects were treated with sevelamer carbonate 1600 mg 3 times daily with meals or calcium acetate 1334 mg 3 times daily during the treatment phase for a total of 12 weeks. All patients received cholecalciferol 400 units daily during the treatment phase of the study. The treatment phase consisted of 5 total study visits: baseline study (day 1 and day 2), week 4, week 8, and week 12. The following assessments and laboratory tests were obtained on day 1: fibroblast growth factor-23 (FGF-23), serum chemistry (calcium, phosphorous albumin, alkaline phosphatase, cholesterol panel), iPTH, 25-OH, 1,25 OH, markers of calcification (fetuin-A, osteoprotegrin), inflammation (IL-6, TNF-α, IL-10, IL-17, INF- γ) and vascular adhesion molecules (sICAM-1, sVCAM-1, P-selectin, E-selectin). Patients were given a urine collection container and instructed to start a 24-hour urine collection. Study subjects would return on day 2 to return their 24-hour urine collection sample, which was analyzed for urinary calcium, phosphorous, protein, and creatinine. The following laboratory assessments were collected during weeks 4 and 8: FGF-23, phosphorous, calcium, and iPTH. The levels of FGF-23, serum chemistry (calcium, phosphorous albumin, alkaline phosphatase, cholesterol panel), iPTH, 25-OH, 1,25 OH, markers of calcification (fetuin-A, osteoprotegrin), inflammation (IL-6, TNF-α, IL-10, IL-17, INF- γ), and vascular adhesion molecules (sICAM-1, sVCAM-1, P-selectin, E-selectin) were assessed at the end of treatment phase (12 weeks).