Progress in pharmacotherapy for the treatment of hyperphosphatemia in renal failure.

ABSTRACT

INTRODUCTION: Among the clinical and metabolic complications of progressive chronic kidney disease (CKD), CKD-mineral bone disorder (CKD-MBD) significantly contributes to morbidity and mortality. While overt and persistent hyperphosphatemia is typical of advanced CKD and requires treatment, other abnormalities of calcium/phosphate metabolism begin to occur since the early stages of the disease. AREAS COVERED We searched on the PubMed database, without restrictions for language or time range, for randomized clinical trials and meta-analyses investigating phosphate-lowering therapies. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. The in-depth knowledge of the characteristics of these drugs is crucial to ensure adequate treatment to CKD patients. EXPERT OPINION A proper control of serum phosphate can be achieved using phosphate binders. These medications may induce side effects. Moreover, data on their impact on clinical outcomes are partly controversial or scarce, especially for the new generation drugs. Hyperphosphatemia favors cardiovascular disease and increases the risk for CKD progression. These effects are partially mediated by fibroblast growth factor 23 (FGF23), a phosphaturic hormone that raises to maintain normal serum phosphate. Since there are no data supporting the use of phosphate-lowering agents when phosphataemia is normal, a key role is played by reducing dietary phosphate intake with the aim to control serum phosphate and the compensatory FGF23 and parathyroid hormone (PTH) increase.

ABSTRACT

PLAIN LANGUAGE SUMMARY: The progressive reduction in renal function, a condition known as chronic kidney disease (CKD), is characterized by several clinical and metabolic complications. Among them are the alterations of calcium and phosphorous metabolism that are part of the so-called CKD-MBD (chronic kidney disease-mineral bone disorder) and contribute to increase morbidity and mortality, especially due to vascular calcification. Persistent hyperphosphatemia is typical of advanced CKD but other abnormalities occur earlier to maintain normal serum calcium and phosphorus levels. These compensatory mechanisms are also involved in the pathophysiology of CKD-MBD and should be counteracted to improve clinical outcomes of CKD patients. Given the crucial role of hyperphosphatemia, numerous therapeutic strategies have been developed over time to help maintain phosphate serum levels within the normal range and prevent or treat CKD-MBD and its consequences. Phosphate binders act by binding dietary phosphate in the gastrointestinal lumen to prevent its absorption. According to their molecular structure, these drugs can be classified into calcium-based (calcium carbonate, calcium acetate), non-calcium-containing (sevelamer carbonate, sevelamer hydrochloride, lanthanum carbonate), aluminum-containing (aluminum hydroxide), and iron-based (sucroferric oxyhydroxide, ferric citrate) compounds. The various phosphate binders show different safety profiles and diverse effects on calcium/phosphate metabolism and vascular calcification. Despite the ability of hyperphosphatemia to favor CKD-MBD development and cardiovascular risk, there are no data supporting the use of phosphate-lowering agents when serum phosphate is normal also due to the potential adverse effects of long-term therapies. Accordingly, a key role is played by reducing dietary phosphate overload since the first stages of CKD.