A clinical trial is required before stopping the use aluminium as a phosphate binder.
sandawana william majoni, Royal Darwin Hospital, P.O. Box 41326, NT Australia, 0810
12 September 2011
Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice? This is a very important question which warrants a rigorous debate and a well conducted clinical trial. Depending on where one is practising nephrology, aluminium is still being used as a phosphate binder but very carefully, if at all, because of the history which has been clearly elucidated in this review article. Aluminium is an important, powerful and well tolerated phosphate binder, the use of which should be revisited since the previous association with very serious complications due to accumulation are now very rare with the use of treated water for dialysis. At present with the available evidence which is comprehensively discussed in this article, it is difficult to easily prescribe this binder but at the same time the evidence is not there to completely discard it on the basis of the current evidence for toxicity. It is very important not to completely discard this without proper evidence. Historically, the are examples of drugs which were discarded on the basis of severe and serious adverse effects but are coming back into clinical practice after careful clinical studies for safety and efficacy and these include thalidomide which is now commonly used for treatment of myeloma and other conditions. The authors practice should be commented for the courage they have shown in continuing to use the binder, albeit with careful monitoring, realising the potential for side effects and at the same time realising its potential for saving lives of dialysis patients. All the current accepted binders have issues. Patients complain that calcium based binders are not palatable despite the various attempts to flavour them. This leads to a number not adhering to the prescribed phosphate binding. This is in addition to the accumulating evidence of exacerbation of vascular calcification; the prevention of which the phosphate binding and bone mineral disorder control is aimed at in the first place. Savelamer has got the same problem with size of tablets being a major issue for some patients and, as mentioned by the authors, available evidence is not strong enough to warrantee using it as the sole binder for lack of outcome data, the high cost and the fact that it is a relatively new binder despite the positive evidence for possible cardiovascular risk reduction. Lanthanum is a new binder, which is still quite expensive and with little experience and no current clinical outcomes data. The available evidence as discussed by the authors point to lack of the best binder and aluminium may well be that binder. As the authors have alluded to, a properly conducted clinical trial comparing currently used ‘safe ‘binders should be carried out and it is feasible for this to be done. This should not just be a clinical trial for proving the safety or otherwise of aluminium as a binder but as mentioned, there is clear evidence that some of the binders we currently use may not be as safe as originally thought and the newer binders are not yet tested. Hard Outcome data is not very robust with the newer binders as well and this will need to be tested. Recently, results of several clinical trials in nephrology have proved that it is not only possible to do large scale clinical trials in nephrology but also that the results may prove that the commonly held views may not be accurate[1-4]. I therefore agree with the authors that the careful use of aluminium is warranted and that a large scale clinical trial will be needed before we can dismiss its use based on a history which may not be related to its use as a phosphate binder at all.
1. Baigent, C., et al., The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet, 2011. 377(9784): p. 2181-92. 2. Cooper, B.A., et al., A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis. New England Journal of Medicine, 2010. 363(7): p. 609-619. 3. Pfeffer, M.A., et al., A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. New England Journal of Medicine, 2009. 361(21): p. 2019-2032. 4. Drüeke, T.B., et al., Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia. New England Journal of Medicine, 2006. 355(20): p. 2071-2084.
A clinical trial is required before stopping the use aluminium as a phosphate binder.
12 September 2011
Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?
This is a very important question which warrants a rigorous debate and a well conducted clinical trial. Depending on where one is practising nephrology, aluminium is still being used as a phosphate binder but very carefully, if at all, because of the history which has been clearly elucidated in this review article. Aluminium is an important, powerful and well tolerated phosphate binder, the use of which should be revisited since the previous association with very serious complications due to accumulation are now very rare with the use of treated water for dialysis. At present with the available evidence which is comprehensively discussed in this article, it is difficult to easily prescribe this binder but at the same time the evidence is not there to completely discard it on the basis of the current evidence for toxicity. It is very important not to completely discard this without proper evidence. Historically, the are examples of drugs which were discarded on the basis of severe and serious adverse effects but are coming back into clinical practice after careful clinical studies for safety and efficacy and these include thalidomide which is now commonly used for treatment of myeloma and other conditions.
The authors practice should be commented for the courage they have shown in continuing to use the binder, albeit with careful monitoring, realising the potential for side effects and at the same time realising its potential for saving lives of dialysis patients. All the current accepted binders have issues. Patients complain that calcium based binders are not palatable despite the various attempts to flavour them. This leads to a number not adhering to the prescribed phosphate binding. This is in addition to the accumulating evidence of exacerbation of vascular calcification; the prevention of which the phosphate binding and bone mineral disorder control is aimed at in the first place. Savelamer has got the same problem with size of tablets being a major issue for some patients and, as mentioned by the authors, available evidence is not strong enough to warrantee using it as the sole binder for lack of outcome data, the high cost and the fact that it is a relatively new binder despite the positive evidence for possible cardiovascular risk reduction. Lanthanum is a new binder, which is still quite expensive and with little experience and no current clinical outcomes data. The available evidence as discussed by the authors point to lack of the best binder and aluminium may well be that binder.
As the authors have alluded to, a properly conducted clinical trial comparing currently used ‘safe ‘binders should be carried out and it is feasible for this to be done. This should not just be a clinical trial for proving the safety or otherwise of aluminium as a binder but as mentioned, there is clear evidence that some of the binders we currently use may not be as safe as originally thought and the newer binders are not yet tested. Hard Outcome data is not very robust with the newer binders as well and this will need to be tested.
Recently, results of several clinical trials in nephrology have proved that it is not only possible to do large scale clinical trials in nephrology but also that the results may prove that the commonly held views may not be accurate[1-4].
I therefore agree with the authors that the careful use of aluminium is warranted and that a large scale clinical trial will be needed before we can dismiss its use based on a history which may not be related to its use as a phosphate binder at all.
1. Baigent, C., et al., The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet, 2011. 377(9784): p. 2181-92.
2. Cooper, B.A., et al., A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis. New England Journal of Medicine, 2010. 363(7): p. 609-619.
3. Pfeffer, M.A., et al., A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. New England Journal of Medicine, 2009. 361(21): p. 2019-2032.
4. Drüeke, T.B., et al., Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia. New England Journal of Medicine, 2006. 355(20): p. 2071-2084.
Competing interests
I have no competing interests.