Skip to main content

Phosphate-Binding Agents Regulate Serum Phosphate and Lower Mortality


June 14, 2012 (Paris, France) –– The use of phosphate-binding agents (PBAs) in hemodialysis patients is associated with reduced mortality risk, regardless of other factors, researchers reported at the XLIX European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress held here in May. The association applied to all types of PBAs except aluminum-containing ones, reported Jorge Cannata-Andia, MD, from the Hospital Universitario Central de Asturias in Oviedo, Spain, who led the European Current Management of Secondary Hyperparathyroidism–a Multicenter Observational Study (COSMOS).
The study, conducted at 220 centers across the European Union, investigated the association between treatments affecting bone metabolic measures and clinical outcomes among hemodialysis patients. Specifically, the researchers looked at the association between the use of phosphate-binding agents as monotherapy or in combination with other agents and mortality.
COSMOS was an observational study with 3 years of follow-up that enrolled patients from a wide geographic area in Europe, in numbers approximately proportional to the number of hemodialysis patients in each country.
According to Dr. Cannata-Andia, COSMOS confirmed the relationship of phosphorus levels and mortality risk seen in previous studies, with the lowest risk for all-cause mortality occurring at a serum phosphorus level near 4.0 mg/dL. Below 3.0 mg/dL, the mortality risk doubled (hazard ratio [HR], 2.0). Similarly, serum phosphorus levels above 5.5 mg/dL were also associated with a higher mortality risk; a 50% increased risk for death (HR of about 1.5) was seen when the serum phosphorus exceeded 6.5 mg/dL.
Similarly, for cardiovascular mortality, the lowest risk was associated with a serum phosphorous level around 4.0 mg/dL, and increased risks were observed at lower and higher levels.
The use of PBAs reduced the risk for all-cause and cardiovascular mortality, in many cases by as much as 50%, regardless of age, sex, history of diabetes or cardiovascular disease, time on hemodialysis, or serum parathyroid hormone, calcium, or phosphorus levels at patients' entrance into the study.
The investigators developed 3 statistical models to study the association between mortality rates and the use of phosphate binders. The models took into account and adjusted for differences in the case mix, case mix plus therapies other than PBAs, and case mix plus other therapies plus blood chemistries.
For each model, all the PBAs (except for aluminum-containing ones) were associated with significantly lower risks for all-cause and cardiovascular mortality. A wide range of PBAs was included, such as those containing calcium or lanthanum, polyanionic gels, calcium or lanthanum plus polyanionic gels, polyanionic gels plus a lanthanum-containing PBA, a calcium- plus aluminum-containing PBA, and polyanionic gels plus an aluminum-containing PBA. The greatest risk reduction — 73% — occurred with the use of a polyanionic gel plus a lanthanum-containing PBA.
"The main message is that phosphate-binding agents are...related with a lower mortality," Dr. Cannata-Andia concluded. He said serum phosphorus above 6.5 mg/dL was associated with greater all-cause and cardiovascular mortality, and "the use of phosphate-binding agents alone or in combination...was associated with significantly lower all-cause and cardiovascular mortality risk, independent of confounders and independent of the use of other drugs, such as calcimimetics or vitamin D, that have previously shown to be associated with lower mortality.... We can say that this effect is from the phosphate binder and is not the effect of vitamin D or a calcium mimetic."
He emphasized that the combination of phosphate-binding agents, which is a common practice, did better than agents used singly.
Dr. Cannata-Andia noted that there are "huge differences in price" between the PBA's. The oldest and least expensive are the aluminum-containing ones, but they are also the ones associated with the highest mortality risks. The newer and more expensive ones are the polyanionic gels and lanthanum-containing PBAs. But he said it is "very reassuring" that good combinations of calcium containing and non-calcium containing phosphate binders "did very well."
Raymond Vanholder, MD, chief of the Nephrology Department at the University Hospital in Ghent, Belgium, and president of the ERA-EDTA, said he was very interested in the study and that it is "beautiful data." But, he commented to Medscape Medical News, that the data "are difficult to grasp for someone who is not in nephrology. So let's summarize that phosphate is a big killer. You can take away that phosphate in many different ways."
He said that in the analysis the researchers corrected for the level of serum phosphorus, which is "a statistical trick to bring [the groups] to the same point... So the nice thing is that there is an association between treatment and outcome. The weak thing is that they correct for this phosphorus. It's good that they correct, but it's not like a randomized controlled trial where everybody starts at the same point."
He said that if one corrects for the level of phosphatemia, then the groups receiving PBAs did better than the patients who did not get them "even for the same level of phosphorus, which I have trouble to understand."
Patients receiving PBAs that contain calcium "are worse off than [those who receive] the drugs that do not contain any calcium, but still, the ones containing calcium are doing better than nothing," Dr. Vanholder noted. "The calcium is tricky in this way that it adds calcium to the bloodstream, and vascular calcium could be a potential mechanism for vascular calcification."
He praised the study for examining many factors and many patients. "[S]o in this way it's certainly useful data. Of course the point is now, how do we outweigh those containing calcium vs those not containing calcium as those containing calcium cost, I think, 10 times less than the other ones."
The study was supported by Fundación Renal Iñigo Alvarez de Toledon and by Amgen. Dr. Cannata-Andia had no other disclosures. Dr. Vanholder did not participate in the study. He receives unrestricted research grants from Fresenius Medical Care and Baxter.

Comments

Post a Comment

Popular posts from this blog

Contact Precautions May Have Unintended Consequences

Contact precautions, including gloves, gowns, and isolated rooms, have helped stem the transmission of hospital pathogens but have also had some negative consequences, according to findings from a new study. Healthcare worker (HCWs) visited patients on contact precautions less frequently than other patients and spent less time with those patients when they did visit, report Daniel J. Morgan, MD, from the University of Maryland School of Medicine and the Veterans Affairs (VA) Maryland Health Care System, Baltimore, and colleagues. Moreover, patients on contact precautions also received fewer outside visitors. "Less contact with HCWs suggests that other unintended consequences of contact precautions still exist," Dr. Morgan and coauthors write. "The resulting decrease in HCW contact may lead to increased adverse events and a lower quality of patient care due to less consistent patient monitoring and poorer adherence to standard adverse event prevention methods (such...
Post a Comment
Read more

Obama Renominates Tavenner to Be CMS Chief

President Barack Obama yesterday renominated Marilyn Tavenner, the acting administrator of the Centers for Medicare & Medicaid Services (CMS), to serve in that post without the caveat of "acting" attached to it. If the Senate approves her nomination, Tavenner will be the first confirmed, full-fledged CMS administrator since Mark McClellan, MD, PhD, stepped down from that position in October 2006, during the George W. Bush administration. Dr. McClellan's successors either were acting administrators or, in the case of Donald Berwick, MD, who was Tavenner's immediate predecessor, a recess appointment. As illustrated by Dr. Berwick's  CMS history , Senate confirmation can be tough to get when one party has enough votes to filibuster and otherwise stymie a nomination by an opposing party's president. That was the case when Obama nominated Dr. Berwick, whom Senate Republicans portrayed as an advocate of healthcare rationing, a characterization denied by t...
Post a Comment
Read more

Secondary Prevention: Clinical Approaches to Managing the Higher-Risk Patient with Heart Disease

INCIDENCE/PREVALENCE/BURDENS ASSOCIATED WITH CARDIOVASCULAR DISEASE (CVD) The prevention of an initial and recurrent cardiovascular event and other complications, such as diabetes and kidney failure [also known as end-stage renal disease (ESRD) or chronic kidney disease (CKD) stage 5] is an important goal in patients with a history of CVD. Each year, approximately 185,000 Americans suffer a recurrent stroke, approximately 470,000 will have a recurrent coronary attack, and an estimated 325,000 will suffer a recurrent myocardial infarction. [1]  Secondary prevention strategies offer the opportunity to prevent further complications and improve outcomes by early detection and management of common comorbidities. The burden on public health and the costs associated with chronic illnesses such as CVD, CKD, and diabetes remain high. An estimated 82.6 million American adults (1 in 3) have 1 or more types of CVD. [1]  Heart failure is the fastest-growing clinical cardiac disease ...
Post a Comment
Read more