Current and potential treatment options for hyperphosphatemia

ABSTRACT

Introduction: Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use.

Areas covered: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption.

Expert opinion: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.

KEYWORDS:

• Chronic kidney disease
• hyperphosphatemia
• phosphate binder
• non-calcium phosphate binders
• safety
• tolerability

Article highlights

• The optimal control of phosphorus levels remains difficult in chronic kidney disease patients.

• Oral phosphate binders can help lower phosphorus levels, but safety and tolerability issues must be considered when selecting which one to use.

• Aluminum is associated with potentially serious toxic risks.

• Calcium-based binders are effective and widely used, but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification.

• A combination of calcium acetate plus magnesium is available, but long-term safety data are lacking as yet.

• Lanthanum is an effective binder which can reduce the progression of vascular calcifications, but the potential effects of long-term tissue deposition are still matter of discussion.

• The resin-based binders, sevelamer carbonate, have profiles that may lead to reduced or no progression of vascular calcifications. Their main side effects are gastrointestinal in nature.

• Iron-based binders could be of clinical importance. In CKD patients not on dialysis, ferric citrate could obviate the need for extra oral iron administration and possibly favoring compliance, while in dialysis patients sucroferric oxyhydroxide could reduce the pill burden without safety concern.

• New agents, which inhibits the active intestinal phosphate transport, are studied as add-on therapy to classic phosphate binders in patients with moderate-to-severe CKD and in patients on dialysis

This box summarizes key points contained in the article.

Declaration of interest

FC and LDV have no conflict of interest to declare. FL was a member of an advisory board and gave lectures at meetings supported by Vifor-Fresenius medical care Pharma. No support was given to this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.