Oral phosphate binders

Abstract

Hyperphosphatemia is an inevitable consequence of end-stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphatemia is observationally and statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range, so the majority of dialysis patients require oral phosphate binders. However, the benefits of achieving the recommended range have yet to be shown prospectively. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminum-containing agents are highly efficient but no longer widely used because of proven toxicity. Calcium-based salts are inexpensive, effective, and most widely used, but there is now concern about their association with hypercalcemia and vascular calcification. Sevelamer hydrochloride is associated with fewer adverse effects, but a large pill burden and high cost are limiting factors to its wider use. Lanthanum carbonate is another non-aluminum, calcium-free phosphate binder. Preclinical and clinical studies have shown a good safety profile, and it appears to be well tolerated and effective in reducing phosphate levels in dialysis patients; however, it is similarly expensive. Data on its safety profile over 6 years of treatment are now published. Achievement of opinion-based guidelines appears to have become an end in itself. Dialysis patient outcomes are worse than outcomes for many types of cancer, yet prospective, outcome-based randomized controlled trials are not being undertaken for reasons that are difficult to explain.

Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients

“…The use of oral phosphate binders to reduce the absorption of dietary phosphate is the mainstay of therapy [1,2]. Phosphate binders must be taken with every meal, often in conjunction with other medications or nutritional supplements, leading to a high pill burden for patients on dialysis [3].…”

Calcium Acetate/Magnesium Carbonate and Cardiovascular Risk Factors in Chronic Hemodialysis Patients

“…Furthermore, in a multivariable analysis, CaMg therapy was negatively associated with progression of LVMI and aortic valve calcification. These data indicate that CaMg therapy - in contrast to calcium-based phosphate binders without Mg [8] - might be able to benefit aortic calcification in HD patients and positively influence CV risk markers, and in this regard, to some extent, even surpasses the calcium-free phosphate binder sevelamer.…”

“…Calcium-based phosphate binders are effective, widely used and inexpensive, but are described to promote hypercalcemia and on their part to accelerate aortic calcification [8]. Calcium-free agents such as sevelamer lower serum phosphate effectively, decrease the calcium burden and are even associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in CKD patients [9], but with a high pill burden and high cost [7].…”

Clinical Efficacy and Cost-Effectiveness of Lanthanum Carbonate as Second-Line Therapy in Hemodialysis Patients in Japan

“…Lanthanum carbonate (LC) is a new nonaluminum, noncalcium phosphate binder with high efficacy, low pill burden, and low toxicity (7,8). However, the cost-effectiveness of LC has not been fully examined.…”