Abstract
Rationale & ObjectiveThere is a concern regarding increased risk of vascular calcification with the use of calcium-based phosphorus binders. This study aimed to compare the effects of sevelamer used as a second-line, low-dose therapy with calcium-based phosphorus binders with those of sevelamer used as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity over 2 years in patients with hyperphosphatemia receiving peritoneal dialysis (PD).Study DesignA 2-year-long prospective, multicenter, open-label, randomized pilot study.Setting & ParticipantsPrevalent patients with hyperphosphatemia receiving PD from 2 university-affiliated hospitals in Hong Kong.InterventionsThe patients were randomized to receive sevelamer either as a first-line therapy at a high dose of 800 mg thrice daily (can titrate up to 1,200 mg thrice daily as required) or a second-line therapy at a low dose of 400 mg thrice daily with calcium carbonate to achieve a serum phosphorus target of ≤5.5 mg/dL.OutcomesThe primary endpoints were changes in coronary artery calcium score and aortic PWV over 104 weeks. The secondary endpoints were changes in heart valve calcium scores, calcification propensity measure, and biochemical parameters of chronic kidney disease–mineral bone disease over 104 weeks.ResultsAmong 60 prevalent patients receiving PD, with a mean age of 53 ± 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; P = 0.21), aortic PWV (mean ± standard error, 0.3 ± 0.1 vs 0.8 ± 0.2 m/s, respectively; P = 0.31), heart valve calcium score, maturation or transformation time, serum calcium levels, and phosphorus levels over 104 weeks were similar for the second-line, low-dose and first-line, high-dose sevelamer groups. Alkaline phosphatase and intact parathyroid hormone levels increased and low-density lipoprotein cholesterol decreased in both the groups, with no significant between-group differences.LimitationsThe sample size was small, and the dropout rates were relatively high.ConclusionsLow-dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with a calcium-based phosphorus binder had similar effects on vascular calcification, valvular calcification, and arterial stiffness compared with high-dose sevelamer used as a first-line therapy. This approach may be considered in resource-constrained countries to minimize calcium loading.FundingThe study was supported by a competitive grant from SK Yee Medical Foundation. T50 assays and other biochemical assays were funded by a research grant from Sanofi Renal Corporation.Trial RegistrationNCT00745589.
Highlights
Vascular and valvular calcification is an important complication in dialysis patients and predicts adverse clinical outcomes 1-3
The results showed that low dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with acalcium-based phosphorus binder had similar outcomes on heart vessels, heart valves calcification, and arterial stiffness compared to higher dose sevelamer used as first-line therapy
Earlier randomized studies suggested that sevelamer may attenuate the Journal Pre-proof progression of coronary and aortic calcification in hemodialysis patients as compared to calcium-based phosphorus binders 4, 5
Summary
Vascular and valvular calcification is an important complication in dialysis patients and predicts adverse clinical outcomes 1-3. Our findings lend important support to the approach that low dose sevelamer hydrochloride 400mg thrice daily may be introduced as a second-line therapy for hyperphosphatemia after calcium-based phosphorus binder is used and serum calcium reached upper limit of laboratory reference to avoid hypercalcemia In this way, more patients may benefit from using sevelamer without adding significant burden to healthcare expenditure and this may facilitate better implementation of KDIGO 2017 CKD-MBD guideline update 26. Sevelamer used as a second-line low dose therapy in combination with calcium carbonate had similar effects on coronary arteries, aortic valve and mitral annulus calcification, aortic stiffness, T50, and biochemical parameters of CKD-MBD over 2 years as first-line higher dose sevelamer therapy in PD patients.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
