Correspondence

Oral Phosphate Binders in Patients with Kidney Failure

N Engl J Med 2010; 363:989-990September 2, 2010

Article

To the Editor:

In their review article on phosphate binders, Tonelli et al. (April 8 issue)1 dismiss aluminum-containing binders because of their well-known toxicity. Yet such drugs remain a cornerstone in the treatment of hyperphosphatemia in most underdeveloped countries. This, of course, is the consequence of the prohibitively expensive alternatives. Furthermore, aluminum toxicity is a problem that becomes manifest after the long-term ingestion of a large amount of aluminum-containing phosphate binders.2 The continuous monitoring of aluminum levels has shown that it is not a great problem today in the Western world.3 Since low-dose aluminum (i.e., 2 g daily) is probably not toxic for patients with a reduced life expectancy (e.g., patients older than 75 years of age receiving dialysis), it would be foolish not to try to cut expenses by administering phosphate binders that contain aluminum. Furthermore, in the Netherlands, aluminum levels are monitored frequently, which would probably detect problems with high levels. I believe it would be wise and cost-effective to determine which dose of aluminum-containing phosphate binders is safe, as determined by aluminum levels.

Geert W. Feith, M.D., Ph.D.
Gelderse Vallei Hospital, Ede, the Netherlands
feithg@zgv.nl

No potential conflict of interest relevant to this letter was reported.

3 References

1. 1

   Tonelli M, Pannu N, Manns B. Oral phosphate binders in patients with kidney failure. N Engl J Med 2010;362:1312-1324
   Full Text | Web of Science | Medline

2. 2

   Martin KJ, Gonzales EA, Slatopolsky E. Renal osteodystrophy. In: Brenner BM, Levine SA, eds. Brenner & Rector's The kidney. 7th ed. Philadelphia: Saunders, 2004:2255-304.
   

3. 3

   Jaffe JA, Liftman C, Glickman JD. Frequency of elevated serum aluminum levels in adult dialysis patients. Am J Kidney Dis 2005;46:316-319
   CrossRef | Web of Science | Medline

To the Editor:

We agree with the main conclusion reached by Tonelli et al. that hard clinical data are lacking to show the superiority of one phosphate binder over another. However, we disagree that in the absence of such data, the least expensive drug should be first in line. Given the paucity of hard-end-point trials for any drug currently given to patients receiving dialysis, we would argue that the physician should evaluate all available evidence. Multiple studies have described the role of calcium in vascular calcification in vitro, and studies involving multiple models of chronic kidney disease in animals have shown that calcium-based phosphate binders are associated with increased arterial calcification and progression of renal disease, as compared with phosphate binders that do not contain calcium.1 None of these studies were included in the review by Tonelli et al. Therefore, the conclusion that the cheapest drug, calcium carbonate, should be used despite the absence of long-term safety studies would mean that cost trumps science. The pendulum has swung too far in the wrong direction, moving us from making decisions on the basis of basic science without clinical proof to the other extreme in which patient managers choose a therapy on the basis of accounting principles alone.

Sharon M. Moe, M.D.
Indiana University School of Medicine, Indianapolis, IN
smoe@iupui.edu

Geoff A. Block, M.D.
Denver Nephrology, Denver, CO

Craig B. Langman, M.D.
Northwestern University Feinberg School of Medicine, Chicago, IL

Drs. Moe, Block, and Langman report receiving consulting fees and grant support from Genzyme; and Drs. Moe and Block, receiving grant support from Shire. No other potential conflict of interest relevant to this letter was reported.

1 References

1. 1

   Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol 2008;19:213-216
   CrossRef | Web of Science | Medline

Author/Editor Response

Feith suggests that our review unduly dismisses aluminum-based agents. We agree that these drugs can lower phosphate levels, but the goal of treatment is to improve clinical outcomes. As stated in our article, the potential for toxicity with aluminum is irrefutable; monitoring aluminum levels is possible but is resource-intensive. We believe that the risks of long-term aluminum use outweigh its potential benefits but recognize that others may disagree.

Moe et al. should acknowledge that the care of dialysis patients in the United States and most other countries is funded by public health care systems within a finite budget. Paying for the speculative benefit of phosphate binders that do not contain calcium means that less money remains to fund therapies known to benefit patients with kidney disease or other conditions. Physicians have the necessary expertise to inform prudent choices about how best to use scarce health care funds. Voluntarily absenting ourselves from such discussions by pretending that economic considerations should be left to “patient managers” means that funding decisions will be made by others whose understanding may be more superficial.

To date, the wide uptake of non–calcium-based phosphate binders has been driven more by marketing than by science. Models in animals and in vitro studies are essential to generate new hypotheses but should not be used to make treatment decisions in humans. Uncritical adoption of unproven therapies removes the incentive for manufacturers to fund properly conducted studies that can determine whether such drugs truly improve outcomes — and does a disservice to our current and future patients. As stated in our article, the theoretical and experimental rationale for non–calcium-based phosphate binders is strong. It is now time to do adequately powered, randomized trials that can inform clinical practice.

Marcello Tonelli, M.D.
Neesh Pannu, M.D.
University of Alberta, Edmonton, AB, Canada
mtonelli@med.ualberta.ca

Braden Manns, M.D.
University of Calgary, Calgary, AB, Canada

Since publication of their article, the authors report no further potential conflict of interest.

Citing Articles (1)

Citing Articles

1. 1

   Alastair J. Hutchison, Craig P. Smith, Paul E. C. Brenchley. (2011) Pharmacology, efficacy and safety of oral phosphate binders. Nature Reviews Nephrology 7:10, 578-589
   CrossRef