Study questions safety and effectiveness of common kidney disease drugs

Longest placebo-controlled trial of phosphate binders conducted to date challenges the drugs' utility

2012-07-20

(Press-News.org) Highlights Phosphate binders, drugs commonly prescribed to patients with chronic kidney disease, may not be as effective as previously thought. Phosphate binders may have negative effects on cardiovascular health. Additional studies are needed on the safety and effectiveness of these drugs.

Washington, DC (July 19, 2012) — Drugs commonly prescribed to patients with chronic kidney disease (CKD) may not be as strongly effective as once thought, and may cause unexpected harm to blood vessels, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings indicate that additional studies on the drugs, called phosphate binders, are needed.

Higher blood levels of phosphorus that are still within the normal range have been linked with heart problems, kidney disease, and premature death. Because the kidneys get rid of excess phosphorus by excreting it through the urine, patients with CKD often have elevated blood phosphorus levels.

Drugs called phosphate binders can lower blood phosphorus levels, and while they are approved only for patients with kidney failure, they are often prescribed off-label to patients with CKD. Geoffrey Block, MD (Denver Nephrology) and his colleagues evaluated the effects of these drugs (calcium acetate, lanthanum carbonate, sevelamer carbonate) in patients with moderate to advanced CKD and normal or near normal blood phosphorus levels.

The study included 148 patients who were randomized to receive one of the three phosphate binders or a placebo. The investigators examined patients after three, six, and nine months of treatment. The study is the longest placebo-controlled trial of phosphate binders in patients with CKD conducted to date.

Treatment with phosphate binders significantly lowered patients' urinary phosphorus levels, moderately lowered their blood phosphorus levels, and slowed progression of a parathyroid disorder that is a common complication of CKD, while treatment with placebo did not. Despite these positive effects, phosphate binders did not have any effect on the blood levels of a hormone that regulates phosphate excretion in the urine, and the drugs caused calcium build-up in blood vessels, which can lead to heart problems. Heart disease is the leading cause of death in patients with CKD.

These findings call into question the safety and effectiveness of phosphate binders in patients with CKD.

"While we continue to believe that serum, or blood, phosphorus is a key component of the increased cardiovascular risk associated with kidney disease, our results suggest the use of the currently approved phosphate binding drugs does not result in substantial reductions in serum phosphorus and may be associated with harm in this population," said Dr. Block. "Future clinical trials should be conducted in all populations with adequate placebo controls and should address alternative or complementary methods to reduce serum phosphorus," he added.

###Study co-authors include David C. Wheeler, MD, Martha S. Persky, Bryan Kestenbaum, MD, Markus Ketteler, MD, David M. Spiegel, MD, Matthew A. Allison, MD, John Asplin, MD, Gerard Smits, PhD, Andrew N. Hoofnagle, MD, PhD, Laura Kooienga, MD, Ravi Thadhani, MD, Michael Mannstadt, MD, Myles Wolf, MD, and Glenn M. Chertow, MD.

Disclosures: GAB: Research Grants (Amgen, Roche, Cytochroma, CMD); Honoraria (Genzyme); Advisory Boards/Consultant (Amgen, Genzyme, KAI, Ardelyx, Mitsubishi); Medical Director (Davita) DCW: Research Grants (Genzyme, Abbott); Honoraria (Amgen, Fresenius, Shire); Adviosry Board (KAI) MSP: Consulting (KAI) BK: Research Grant (Amgen) MK: Research Grants (Amgen, Abbott); Honoraria (Amgen, Abbott, Genzyme, FMC, Medice, Shire); Payment for Development of Educational Presentations (Amgen, Abbott); Consultant (Amgen, Abbott, Genzyme, FMC, Medice, Shire); DMS: Research Grants (Amgen, Keryx); Honoraria (Amgen, Sanofi); Advisory Boards (Affymax, Amgen, Sanofi); Consultant (Amgen) MAA: None JA: Employee (LabCorp); Consultant (Oxthera Corp) GS: None ANH: Research Grants (Waters); Consultant (Onconome) LK: None RT: Research Grant (Abbott); Consultant (Fresenius North America, Mitsubishi Tanabe); Honoraria (Shire) MM: None MW: Research Grants (NIH, Shire, Amgen, Genzyme); Honoraria (Abbott, Genzyme, Shire); Consultant (Abbott, Genzyme, Luitpold, Mitsubishi, Cytochroma, Biotrends, Ardelyx, Astellas); GMC: Research Grant (NIDDK, Amgen, Reata); Advisor (Ardelyx)

The article, entitled "A Randomized Trial of Phosphate Binders in Patients with Moderate Chronic Kidney Disease," will appear online at http://jasn.asnjournals.org/ on July 19, 2012, doi: 10.1681/ASN.2012030223.

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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Study questions safety and effectiveness of common kidney disease drugs

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