Sunday, August 5, 2012

Kidney Drugs May Harden Arteries

Phosphate binders can lower serum phosphorus levels for patients with chronic kidney disease (CKD), but they may also increase vascular calcification, researchers found.
Patients taking one of three different phosphate binders had a significant drop in serum phosphorus from baseline compared with placebo (4.2 mg/dL to 3.9 mg/dL, P=0.03), according to Geoffrey Block, MD, of Denver Nephrology, and colleagues.
But patients receiving the binders also developed significantly more coronary artery and abdominal aorta calcification compared with those on placebo (P=0.05 and P=0.03, respectively), they reported online in the Journal of the American Society of Nephrology.
"The safety and efficacy of phosphate binders in patients with CKD and normal serum phosphorus remains uncertain," they wrote.
Three phosphate binders are currently approved to treat hyperphosphatemia in patients with end-stage renal disease (ESRD): calcium acetate (Phoslo), lanthanum carbonate (Fosrenol), and sevelamer carbonate (Renvela).
None is approved for patients with CKD who aren't on dialysis, but because higher serum phosphorus concentrations have been linked to greater mortality, some clinicians have proposed using them in that patient population as well.
Block and colleagues randomized 148 patients with an estimated glomerular filtration rate (eGFR) of 20 to 45 ml/min per 1.73 m2 to placebo or one of the three active agents.
They found that patients on phosphate binders had significantly greater reductions in serum phosphorus than those on placebo. From a baseline level of 4.2 mg/dL in both groups, levels fell to 3.9 mg/dL in the active group compared with 4.1 mg/dL for those on placebo (P=0.03).
When looking at the phosphate binders individually, however, only patients on lanthanum carbonate had significant reductions compared with placebo (P=0.04).
Binders also significantly lowered urinary phosphorus compared with placebo -- patients on the drugs saw a 22% drop in levels compared with no change for those on placebo (P=0.002).
Parathyroid hormone concentrations remained stable with active therapy and rose 21% among those on placebo (P=0.002), while vitamin D concentrations fell significantly with binder use (P=0.004).
Blood levels of C-terminal fibroblast growth factor 23 concentrations (FGF23), a marker associated with progression to ESRD and mortality, were elevated in all groups at baseline, but there were no significant changes in this parameter between any of the groups overall.
Patients on sevelamer carbonate, however, saw significant declines in FGF23 (P=0.02 versus placebo), while those on calcium acetate had significant increases (P=0.03 versus placebo).
Data on vascular calcification changes was available for 96 patients. Among those whose calcium scores were above zero at baseline, binders significantly increased calcium volume scores of both the coronary artery (18.1% versus 0.6%, P=0.05) and abdominal aorta (15.4% versus 3.4%, P=0.03).
The researchers noted that the effects on vascular calcification were most pronounced for patients in the calcium acetate group.
The study's single-center nature limits its generalizability, the researchers wrote, and they cautioned that they didn't standardize the time of day at which they measured serum phosphorus or calcium levels. They also did not attempt to control dietary phosphorus or calcium intake and did not control for season or sun exposure.
Nonetheless, the authors concluded that although phosphate binders appear to lower phosphorus levels, the drugs also increase vascular calcification; thus making their use in CKD patients not on dialysis uncertain.
The researchers reported relationships with Amgen, Roche, Cytochroma, CMD, Genzyme, KAI, Ardelyx, Mitsubishi, Davita, Abbott, Fresenius, Shire, FMC, Medice, Keryx, Sanofi, Affymax, LabCorp, Oxthera Corp, Waters, Onconome, Luitpold, Biotrends, Astellas, and Reata.
Primary source: Journal of the American Society of Nephrology
Source reference:
Block GA, et al "Effects of phosphate binders in moderate CKD" J Am Soc Nephrol 2012; DOI: 10.1681/ASN.2012030223.
Kristina Fiore
Staff Writer
Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine.

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