Resource-limited areas may consider low-dose sevelamer as therapy for hyperphosphatemia
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Low-dose sevelamer in combination with a calcium-based phosphorus binder may be used in resource-constrained countries as a second-line therapy for patients with hyperphosphatemia to minimize calcium loading.
According to data published in Kidney Medicine, a low dose of sevelamer as a second-line therapy revealed no significant differences than a higher-dose sevelamer as first-line therapy.
“Due to cost constraints, a sevelamer-based phosphorus binder is not reimbursed in many middle-income or low-income countries and many patients could not afford self-financing long-term use of sevelamer. Although it remains uncertain whether any phosphorus binders use may impact hard outcomes in dialysis patients, increasing data suggested that restricting the dose of calcium-based phosphorus binder in kidney failure patients may be associated with more favorable clinical outcomes compared with use of high-dose calcium-based phosphorus binder,” Angela Yee-MoonWang, MD, PhD, from the department of medicine in Queen Mary Hospital at The University of Hong Kong in Hong Kong, told Healio. “If sevelamer used as a second-line low-dose therapy (thus allowing a restricted dose of calcium-based phosphorus binders to be used to avoid hypercalcemia) was equally effective in controlling biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and limiting vascular calcification and arterial stiffness as first-line higher-dose sevelamer therapy, this regimen could be cost-saving for many emerging countries or countries that do not reimburse the drug cost.”
Wang and colleagues observed 60 patients with hyperphosphatemia who received peritoneal dialysis (PD) from two university-affiliated hospitals in Hong Kong during the prospective multicenter open-label randomized pilot study. Patients were randomized to receive either sevelamer hydrochloride as a first-line higher-dose 800 mg thrice daily (can titrate up to 1200 mg thrice daily as required) treatment or a second-line low-dose 400 mg thrice daily treatment after calcium carbonate to achieve a serum phosphorus target at least 5.5 mg/dL.
Physicians met with patients every 3 months to reinforce dietary adherence to phosphorus restrictions, and at each 12-week follow-up, researchers measured patients’ systolic and diastolic blood pressure.
“This study aimed to compare sevelamer use as first-line higher-dose therapy vs. sevelamer use as a second-line low-dose therapy with calcium-based phosphorus binders on coronary arteries and aortic pulse wave velocity (PWV) (as study primary endpoints) and heart valves calcification, calcification propensity and biochemical parameters of CKD-MBD (as secondary endpoints) over 104 weeks in PD patients with hyperphosphatemia,” Wang told Healio.
Researchers found changes in coronary artery calcium score, aortic valve calcium score, mitral annulus calcium score, T50, serum calcium, phosphorus and the proportion of rapid progressors did not differ between the two groups for 104 weeks.
Additionally, alkaline phosphates and intact parathyroid hormone increased, and LDL-cholesterol decreased in both groups with no significant between-group differences.
“Our findings are applicable and relevant contemporary references for real clinical practice, especially in countries with limited health resources and cost constraints that may prohibit the first-line use of high-dose sevelamer,” Wang told Healio. “Our findings lent important support that low-dose sevelamer hydrochloride 400 mg thrice daily may be introduced as a second-line therapy for hyperphosphatemia after calcium-based phosphorus binder was 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 health care expenditure and this may facilitate better implementation of [Kidney Disease Improving Global Outcomes] 2017 CKD-MBD guideline update. Our data should be applicable and generalizable to other PD population worldwide.”
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