Phosphorus Binders for Hyperphosphatemia Treatment

Phosphorus Binders for Hyperphosphatemia Treatment In the population of 385 individuals that have developed end stage renal disease in the United States, about 250,000 individuals have a condition called hyperphosphatemia (Fink Vincent, 2011, p. 194). This condition is defined by â€Å"a serum phosphate level above 4.5 mg/dL; it may be clinically significant at levels over 5 mg/dL† (Fink Vincent, 2011, p.195). People with kidney disease are not able to filter out phosphorus anymore, therefore resulting in excess amounts of it (Malberti, 2013). Phosphorus in small quantities are good for the body; however, if the level of phosphorus exceeds a certain amount, it can be dangerous because it can deplete calcium, which is essential to the body (Fink Vincent, 2011). An excess results in a gland in the neck to release a hormone which releases calcium out of the bones. Hence, the bones turn weak and brittle, which can eventually lead to bone diseases (National Kidney Foundation, Inc., 2013). Kidney failure leads to increases in ser um levels of phosphorus. In the absence of end-stage renal disease, hyperphosphatamia is treated with â€Å"phosphate excretion using saline infusion (volume diuresis) and diuretic administration† (Fink Vincent, 2011). Drugs used to treat this are oral phosphate binders, since they decrease the absorption of phosphate (Provider Synergies, L.L.C., 2009). In the paper, the different types of phosphorus binders that are used to treat patients with hyperphosphatemia caused by End Stage Renal Disease and how does their chemical composition affect their effectiveness as drug will be explored. A wide range of phosphate binders is currently available for the treatment of hyperphosphatemia in CKD patients. These agents are generally divided into two main classes: calcium-based binders (calcium carbonate and acetate) and calcium-free binders (aluminum hydroxide, lanthanum carbonate, magnesium carbonate) (Malberti 2013). Since current phosphate binders are similar in the effectiveness of lowering serum phosphorus levels, the main considerations are the adverse reactions, gastrointestinal tolerability, absorbability, and cost-effectiveness (Malberti, 2013). Aluminum hydroxide is a potent phosphate binder, but â€Å"concern about skeletal, hematological and neurological toxicity led to a favored use of calcium salts (carbonate and acetate) in the 1990s† C. The KDIGO recommend avoiding long term use of aluminum hydroxide especially in patients with chronic kidney disease stages three to five (Malberti, 2013). Calcium acetate and calcium carbonate are often considered curre nt standard therapy, since they very effectively lower serum phosphorus levels. Thus, these two calcium-containing binders can be considered comparable for efficacy in control of hyperphosphatemia, effects on mineral metabolism restrictions and tolerability (Provider Synergies, L.L.C., 2009). Sevelamer carbonate has shown comparable efficacy and safety to sevelamer hydrochloride in dialysis patients and is indicated to lower serum phosphorus also in hyperphosphatemic chronic kidney diseases stage 3–5 patients not on dialysis (Provider Synergies, L.L.C., 2009). Dose titration of sevelamer can help patients with either chronic kidney disease stages 3–5 reach a high rate of phosphate control (Arroyo et al., 2014). Lanthanum carbonate is a non-calcium-based phosphate binder supplied as a chewable tablet of three dosage strengths (500, 750 and 1,000 mg of elemental lanthanum) that has been shown to be effective in reducing phosphorus in short-term clinical trials (Malberti, 2013). Calcium and aluminum salts are commonly used. Nevertheless, calcium salts can lead to hypercalcemia and metastatic calcification because of high calcium-phosphorus (Ca Ãâ€" PO4) and aluminum salts are very toxic (Malberti, 2013). Chronic management of hyperphosphatamia included treatments with calcium-free phosphate binders like sevelamer hydrochloride [Renagel] which may reduce long-term mortality by preventing the cardiovascular complications that associated with a high Ca Ãâ€" PO4 product (Provider Synergies, L.L.C., 2009). In 2003, the National Kidney Foundation released rules and guidelines about how to manage hyperphosphatemia and bone-related disorders in patients with renal impairment (NIH., 2012). The Kidney Disease Quality Outcome Initiative (NKF-K/DQOIâ„ ¢) states that patients who are on dialysis should have serum phosphorus levels between 3.5 to 5.5 mg/dL (1.13 to 1.78 mmol/L) (National Kidney Foundation, Inc., 2012). Treatment options include â€Å"reduction of di etary phosphorus, phosphate binding therapy, and removal of phosphorus by dialysis† (Provider Synergies, L.L.C., 2009). Magnesium carbonate (MgCO3) is a phosphorus binder with advantages in terms of cost, safety and tolerance and it has a similar efficacy to other drugs. This source assess the effects of replacing aluminum hydroxide [Al(OH3)] with MgCO3to help treat patients with hyperphosphatemia (Malberti, 2013). MgCO3 is another type of phosphorus binder but is not as commonly used as calcium acetate or sevelamer hydrochloride (Malberti, 2013). Twenty- one patients with â€Å"phosphorus 3) as the only binder. Then there was a conversion to MgCO3 â€Å" (Arroyo et al, 2014). Hyperphosphatemia decreased from 4.52 ±0.99 to 4.02 ±1.07mg/ dl (P=.027),. In patients who were previously taking MgCO3allowed good control of serum phosphorus in hemodialysis patients who were previously well controlled with Al(OH3), MgCO3 â€Å"permitted good control of serum phosphorus levels even though there was a slight increase in serum magnesium†, but that had short-term clinical significance (Arroyo et al, 2014). Aluminum hydroxide is a powerful binder and was historically used to treat patients with hyperphosphatemia, but because of its high toxicity levels (Floege et al. 2014). Patients were selected from a hemodialysis unit that had adequate control of serum phosphorus levels and were on Al(OH)3 binder monotherapy and required continuation (Arroyo et al, 2014). A study was conducted that tested the efficiency of a new iron-based phosphate binder. PA21 (sucroferric oxyhydroxide), a â€Å"novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of sevelamer carbonate in randomized, controlled phase III study† (Floege et al. 2014). Seven hundred and seven hemodialysis and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0à ¢Ã¢â€š ¬Ã¢â‚¬ °g per day and 348 received sevelamer 4.8–14.4à ¢Ã¢â€š ¬Ã¢â‚¬ °g per day for an 8-weeks, followed by 4 weeks without dose change, and then 12 weeks maintenance (Floege et al. 2014). Efficacy was maintained to week 24. â€Å"Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with sevelamer† and he PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control (Floege et al. 2014). Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to sevelamer carbonate, a lower pill burden, and better adherence (Floege et al. 2014). PA21 (sucroferric oxyhydroxide) is a â€Å"new calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder with a high phosphate binding capacity over a wide pH range† (Pennick et al 2012).12 It is formulated as flavored, chewable tablets that disintegrate easily in the gastrointestinal (GI) tract, bind phosphate across the whole physiologically relevant pH range, each contain 500à ¢Ã¢â€š ¬Ã¢â‚¬ °mg of iron, and may be taken without water (Floege et al. 2014). Phosphorus binders decrease the absorption of phosphorus in the gastrointestinal tract (Provider Synergies, L.L.C., 2009). They are â€Å"simple molecular entities but can also be polymeric structures that bind with phosphorus in the body and form an insoluble compound† (Provider Synergies, L.L.C., 2009). Some binders work as a sponge and soak up the phosphorus in foods while others bind to the phosphate and are then excreted (NIH., 2012). Calcium-containing salts are used to bind with phosphorus and to increase calcium levels. The most commonly used calcium containing salt is calcium acetate (PhosLo) (Provider Synergies, L.L.C., 2009). Sevelamer (Renagel, Renvela) is a non-calcium, non-aluminum, non-magnesium, non-absorbable hydrogel that binds phosphorus. Sevelamer comes in two salt forms – sevelamer hydrochloride (Renagel) and sevelamer carbonate (Renvela) (Provider Synergies, L.L.C., 2009). Sevelamer yields the same reduction in serum phosphate levels as calcium ace tate but does not have the same risk of hypercalcemia since it does not contain calcium. Lantanum carbonate (Fosrenol) is another phosphate binder (Provider Synergies, L.L.C., 2009). Lantanum has a high affinity for phosphorus and is part of the lanthanide series. It reacts with phosphorus to form the insoluble compound lanthanum phosphate(Provider Synergies, L.L.C., 2009). When calcium acetate and sevelamer hydrochloride were compared for efficiency, 84 patients were randomized to calcium acetate or sevelamer for eight weeks (Arroyo et al., 2014). A similar result was observed between the calcium acetate and sevelamer (sevelamer -2.0 ±2.3mg/dL versus calcium acetate -2.1 ±1.9 mg/dL) (Arroyo et al., 2014). However, Hypercalcemia (serum calcium >11 mg/dL) was observed in 22 percent of patients receiving calcium acetate (Provider Synergies, L.L.C., 2009). These are the various types of phosphorus binders used to treat patients with hyperphosphatemia caused by End Stage Renal Disea se. The chemical composition affects their cost, toxitity, and how they work inside the body. There are new discoveries as discussed about the iron based phosphorus binder. This type of phosphate binder is being tested further in clinical trials to make it available to the masses.