PPIs Plus Phosphate Binders May Decrease Phosphorus Levels in Hemodialysis Patients

Deborah Brauser

April 29, 2010

Dr. Jacob Poulose

April 29, 2010 (Orlando, Florida) — Taking a proton pump inhibitor (PPI) with a phosphate binder might improve phosphorus control in patients on hemodialysis, according to a retrospective study presented here at the National Kidney Foundation (NKF) 2010 Spring Clinical Meetings.

"Contrary to expectations and unlike previous studies, no negative effect of concurrent PPI use with a phosphate binder was demonstrated," said investigative team member Jacob Poulose, a third-year medical resident at the New York Medical Hospital Center in Queens.

"Adding PPIs did not reduce the efficacy of phosphate control in these patients; in fact, we saw potential benefit," he noted.

Goal: Lowering Phosphorus Levels

High phosphorous levels are a risk factor for cardiovascular events, such as stroke and heart disease, reported Mr. Poulose.

He said that a small prospective study recently conducted in Japan looked at PPIs and H2 antagonists with phosphate binders and found a negative effect. "Over a 3-month period, those investigators found a loss of phosphate control. We wanted to recreate parts of that study to see if we got the same results."

For this study, Mr. Poulose and colleagues sought to compare whether PPIs combined with the calcium-based binder calcium acetate (667 mg tablet) or with the noncalcium-based binder sevelamer hydrochloride (800 mg tablet) would lower phosphorus levels.

Data from 108 hemodialysis outpatients were evaluated and their phosphorus levels were examined over a 3-month period. The patients were subdivided on the basis of the therapy they were taking: calcium acetate plus PPI (n = 19), calcium acetate without PPI (n = 25), sevelamer plus PPI (n = 18), and sevelamer without PPI (n = 46).

The primary end point was phosphorus control, defined as an average phosphorus level below 6 mg/dL and "a calcium × phosphate product level less than 55." Pill burden, defined as "total number of individual phosphate binders taken daily," was a secondary end point.

Best Results Seen With PPI Plus Sevelamer

Results showed that significantly more patients taking a PPI plus a phosphate binder achieved phosphorus control than did those taking only a phosphate binder (76% vs 24%; P = .001).

In addition, more patients in the sevelamer plus PPI group achieved phosphorus control than in the sevelamer only group (88% vs 61%; =.037).

No significant difference was found in phosphorus control between the calcium acetate plus PPI and calcium acetate only groups.

For patients taking fewer than 6 tablets, those in the sevelamer plus PPI group had a lower daily pill burden than those in the sevelamer only group (93% vs 57%; P = .016).

"Overall, our data suggest that there is a potential benefit in the use of PPIs with a noncalcium-based phosphate binder in the control of phosphorus level in hemodialysis patients," said Mr. Poulose. "Of course, a prospective study still needs to be done to further ascertain this benefit."

PPIs Appear Safe for Hemodialysis Patients

"This is an interesting study because it does contradict previous studies," said Leslie Spry, MD, kidney specialist at the Dialysis Center of Lincoln and at Lincoln Nephrology and Hypertension in Nebraska, and a spokesperson for the NKF.

"However, all of their significant data appear to be settled in the sevelamer group, which is sevelamer hydrochloride," added Dr. Spry, who was not involved with this study.

"Hydrochloride has long been known to be associated with some acidosis, and [the results] may have something to do with that, but unfortunately that particular formulation is going to go away. So the conclusions here related to sevelamer hydrochloride will no longer be pertinent because it's going to be taken off the market and replaced with sevelamer carbonate," he explained.

Dr. Spry noted that he would next like to see if the investigators can duplicate these data with sevelamer carbonate. "Were the good results here due to sevelamer or was it the hydrochloride? Because of its charge, hydrochloride can maintain binding in a less than acid environment, but can sevelamer carbonate maintain its binding in that environment? If so, do you negate the effect when you add a PPI? I don't know, but that's a study I'd be interested in seeing."

"Nevertheless, the take-home message from this study is that clinicians shouldn't be afraid of PPIs. There were some previous studies that did suggest some decreased binding, but all of those have been relatively small. I think the bottom line is that PPIs shouldn't be feared in our dialysis folks," concluded Dr. Spry.

Dr. Poulose and Dr. Spry have disclosed no relevant financial relationships.

National Kidney Foundation (NKF) 2010 Spring Clinical Meetings: Abstract Poster 180. Presented April 14, 2010.


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