Beyond foods and drinks, medications may be a significant source of phosphate that adds to patients' daily load. A new study finds several medications prescribed to chronic kidney disease (CKD)patients, particularly long-term ones, contain absorbable phosphate.

Investigators led by Gianluca Trifiro, MD, Assistant Professor of Pharmacology at the University of Messina in Milan, Italy, identified 1,989 CKD patients from the Arianna database, a local health database of almost 400,000 people living in Southern Italy. All drug prescriptions provided to these patients were evaluated and classified as to whether they contained absorbable phosphate, their dosage, and route of administration. The researchers also determined where the absorbable phosphate resided in the drug: in the active ingredients, in the counter-ion, or in the excipient (typically, a pharmacologically inert binder).

Of all medicinal products prescribed to CKD patients, only 9% contained phosphate, according to findings published in Nutrition, Metabolism & Cardiovascular Diseases. Yet 70% of CKD patients were prescribed at least 1 medication containing absorbable phosphate during the 6 years of follow up. Their usage was higher than that of non-CKD patients.

Additional findings highlight a concerning degree of exposure. Most CKD patients were prescribed phosphate-containing drugs targeting the gastrointestinal or cardiovascular system. Duration of use was typically long-term: a median 232 and 224 days, respectively. Additionally, many medications were taken orally, the most common route of the drugs with absorbable phosphate.

Results also suggested that patients with advanced CKD may have a higher phosphate burden than those with early stage CKD. About 10% of patients with CKD stages 4–5 had an estimated intake of 80 mg or more phosphate a day from medication, which is considered high, and 2% had an estimated intake of 150 mg or more. The investigators estimated that these amounts represent 13% and 25% excess phosphate intake per day, respectively.

“In patients with renal disease it is essential to reduce blood phosphate levels as hyperphosphatemia has been shown to increase the risk of cardiovascular-related morbidity,” the researchers stated. “The biochemical mechanism for this is likely to be triggered in early CKD stages as the reduced capacity of the kidney to excrete phosphate stimulates the release of fibroblast growth factor 23 (FGF-23) which in turn promotes renal phosphate excretion in order to maintain homeostasis.”

In 94% of the medications examined, the source of absorbable phosphate was the excipient of the drug, not the active components. This fact has several important implications. For example, exact amounts of phosphate may not be listed in products. Given this lack of detail, clinicians have no way of making informed medication choices for their patients. Substituting phosphate-free excipients is a potential solution that should be explored, according to the investigators

1. Sultana, J; Musazzi, UM; Ingrasciotta, Y; et al. Nutrition, Metabolism & Cardiovascular Diseases, June 2015; doi: 10.1016/j.numecd.2015.06.001.

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Beyond foods and drinks, medications may be a significant source of phosphate that adds to patients' daily load. A new study finds several medications prescribed to chronic kidney disease (CKD)patients, particularly long-term ones, contain absorbable phosphate.

Investigators led by Gianluca Trifiro, MD, Assistant Professor of Pharmacology at the University of Messina in Milan, Italy, identified 1,989 CKD patients from the Arianna database, a local health database of almost 400,000 people living in Southern Italy. All drug prescriptions provided to these patients were evaluated and classified as to whether they contained absorbable phosphate, their dosage, and route of administration. The researchers also determined where the absorbable phosphate resided in the drug: in the active ingredients, in the counter-ion, or in the excipient (typically, a pharmacologically inert binder).

Of all medicinal products prescribed to CKD patients, only 9% contained phosphate, according to findings published in Nutrition, Metabolism & Cardiovascular Diseases. Yet 70% of CKD patients were prescribed at least 1 medication containing absorbable phosphate during the 6 years of follow up. Their usage was higher than that of non-CKD patients.

Additional findings highlight a concerning degree of exposure. Most CKD patients were prescribed phosphate-containing drugs targeting the gastrointestinal or cardiovascular system. Duration of use was typically long-term: a median 232 and 224 days, respectively. Additionally, many medications were taken orally, the most common route of the drugs with absorbable phosphate.

Results also suggested that patients with advanced CKD may have a higher phosphate burden than those with early stage CKD. About 10% of patients with CKD stages 4–5 had an estimated intake of 80 mg or more phosphate a day from medication, which is considered high, and 2% had an estimated intake of 150 mg or more. The investigators estimated that these amounts represent 13% and 25% excess phosphate intake per day, respectively.

“In patients with renal disease it is essential to reduce blood phosphate levels as hyperphosphatemia has been shown to increase the risk of cardiovascular-related morbidity,” the researchers stated. “The biochemical mechanism for this is likely to be triggered in early CKD stages as the reduced capacity of the kidney to excrete phosphate stimulates the release of fibroblast growth factor 23 (FGF-23) which in turn promotes renal phosphate excretion in order to maintain homeostasis.”

In 94% of the medications examined, the source of absorbable phosphate was the excipient of the drug, not the active components. This fact has several important implications. For example, exact amounts of phosphate may not be listed in products. Given this lack of detail, clinicians have no way of making informed medication choices for their patients. Substituting phosphate-free excipients is a potential solution that should be explored, according to the investigators

1. Sultana, J; Musazzi, UM; Ingrasciotta, Y; et al. Nutrition, Metabolism & Cardiovascular Diseases, June 2015; doi: 10.1016/j.numecd.2015.06.001.

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