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Phosphate-Binding Drug Does Not Improve Heart Health of Patients with Mild Kidney Disease

Posted by dlife on Thu, Apr 18, 13, 05:29 PM 0 Comment

April 18, 2013 (Newswise) — High phosphate levels in the blood carry increased heart-related risks, but taking a drug that targets phosphate does not improve cardiovascular measures in patients with mild kidney disease, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that, at least for now, reducing dietary intake of phosphate may be the best way for these patients to reduce the mineral's effects on the heart.

Higher blood levels of phosphate, even in the normal range, are linked with an increased risk of dying from heart-related causes. This was first demonstrated in patients with chronic kidney disease (CKD) and subsequently in the general population. Researchers have suggested a number of possible explanations, including phosphate's ability to promote calcification and stiffening of blood vessels and its potential to cause structural changes in the heart, such as increased wall thickness.

To see if lowering phosphate levels in the blood may help lower cardiovascular risks, Charles Ferro, MBChB, MD, Colin Chue, MBChB (University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, in England), and their colleagues designed a double-blind, randomized, placebo-controlled trial of 120 patients with early stage CKD that tested the effects of the phosphate binder sevelamer carbonate, which is approved only for patients with kidney failure. The researchers looked to see if the drug might reduce heart muscle thickness and decrease markers of blood vessel stiffness after 40 weeks of treatment.

"We hoped that by asking a very motivated group of patients with early stage chronic kidney disease to take phosphate binders with every meal, we would be able to reduce the amount of phosphate absorbed from the diet," explained Dr. Ferro.

At the end of the study, the investigators found no differences in any of the measures of cardiovascular structure and function between the groups. However, only 56% of patients took more than 80% of the study medication. When the sub-group of patients with more than 80% compliance was analyzed separately, the group taking sevelamer excreted significantly smaller amounts of phosphate in their urine compared with those taking placebo. The sevelamer group also had reduced levels of a hormone called FGF-23, which is critical for maintaining phosphate balance but is also toxic to the cardiovascular system. No changes were noted in any of the measures of cardiovascular structure, though.

"It would appear that for now it would be better to lower the amount of phosphate in the diet rather than rely on pharmacological interventions," said Dr. Ferro. Foods with large amounts of added phosphate are processed meat, ham, sausages, canned fish, baked goods, cola drinks, and other soft drinks. "Fast food and ready-to-eat processed foods are the main contributors to today's rising dietary consumption of phosphate," Dr. Ferro noted. He suggested that a comprehensive public education effort that explains the harmful effects of high phosphate intake and provides clear labeling of the phosphate content of food could help limit the damage done by this newly recognized cardiovascular risk factor.

In an accompanying editorial, Rajiv Agarwal, MD (Indiana University School of Medicine) noted that the study "should not serve as a death knell to investigations on phosphorus in progressive CKD, but should instead serve as a crèche for future investigations on the value of phosphorus reduction in preventing cardiovascular disease and CKD progression."

Study co-authors include JonathanTownend, MBChB, MD, William Moody, MBChB, Daniel Zehnder, MD, PhD, Nadezhda Wall, MBChB, Lorraine Harper, MBChB, PhD, Nicola Edwards,MBBS,PhD, and Richard Steeds, MBBS, MD.

Disclosures: This study was funded by an unrestricted grant from Genzyme Corporation. Genzyme Corporation provided the study drug sevelamer carbonate and matching placebo. Genzyme Corporation had no role in study design or data analysis and interpretation. Dr. Ferro and Dr. Chue have received lecture and advisory board fees from Genzyme Corporation.

The article, entitled "Cardiovascular Effects of Sevelamer in Stage 3 CKD," will appear online at http://jasn.asnjournals.org/ on April 18, 2013, doi: 10.1681/ASN.2012070719.

The editorial, entitled "What Can We Learn from Null Randomized Controlled Trials?" will appear online at http://jasn.asnjournals.org/ on April 18, 2013, doi: 10.1681/ASN.2013030295.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Founded in 1966, and with more than 13,500 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.

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