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Patients on dialysis are at risk of developing hyperphosphatemia, a serious and potentially life-threatening condition. A new study looks at factors that may influence the clinical effectiveness of drugs which aim to lower blood phosphate levels.
People with late-stage chronic kidney disease (CKD) have problems with removing phosphate from their bodies, leading to increased levels in their blood. This condition, known as hyperphosphatemia, can make patients receiving dialysis feel very ill and put them at an increased risk of death.
Treatment with drugs that bind phosphate in the gastrointestinal (GI) tract aim to reduce its absorption into their bloodstream. But many patients still don’t reach the target levels for blood phosphate, despite taking phosphate binders and restricting their diet.
The reasons why phosphate-binding treatments don’t always have the desired effects are complex, but they may include patients not taking the drugs correctly, not following their diet, or the phosphate coming from elsewhere in the body, such as from their bones. However, factors that influence the ability of phosphate binders to bind phosphate may also have an impact.
A team of researchers carried out a series of laboratory tests to explore the influence of pH and phosphate concentration on the phosphate-binding capabilities of five existing drugs used to treat patients with hyperphosphatemia.1
To do this, they measured the phosphate-binding capacity of each drug in solutions with different pH values and phosphate concentrations. An ELGA PURELAB flex water purification system provided the ultrapure water for making all phosphate solutions and pH media.
All five drugs bound more phosphate within solutions containing higher concentrations of phosphate and, with the exception of one drug, they also performed better in the more acidic solutions. However, the differences were all small except for lanthanum carbonate, which doubled it binding capacity at pH 3.0.
Although more work will be needed to find out if these laboratory results extrapolate to the complex GI environment where additional factors such as the presence of bile salts, passage time through the stomach and intestines, or the use of food additives, may introduce more variability into a drug’s phosphate binding capacity.
But should they hold true within the body, the influence of pH may be particularly relevant as the levels of stomach acidity in a patient could impact on drug effectiveness. Doctors would, therefore, need to consider other factors that may affect this, such as if a patient is also taking proton pump inhibitors, has just eaten a meal, or are experiencing chronic gastritis.
The results from this study shed new light on the pharmacology of phosphate-binding drugs and could help improve the treatment for patients with end-stage kidney disease in the future.
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Schumacher, S. P., et al., Influence of pH and phosphate concentration on the phosphate binding capacity of five contemporary binders. An in vitro study. Nephrology 2018, Feb 26. doi: 10.1111/nep.13245