Do Aluminium-based Phosphate Binders Continue to Have a Role in Contemporary Nephrology Practice?

David W Mudge; David W Johnson; Carmel M Hawley; Scott B Campbell; Nicole M Isbel; Carolyn L van Eps; James JB Petrie

Disclosures

BMC Nephrology. 2011;11 

In This Article

Summary

In summary, the historical data which have raised concern about neurological and bone toxicity of aluminium-based phosphate binders may no longer be relevant to contemporary practice. This is due largely to the more rigorous treatment and testing of dialysis water in most haemodialysis units, and also the regular measurement of serum aluminium levels in dialysis patients taking aluminium binders. However, due to the difficulties in measuring aluminium accumulation in humans directly, toxicity of aluminium remains a concern. Serum aluminium levels in dialysis patients receiving aluminium binders are higher than in those not receiving aluminium binders, suggesting some accumulation, the toxicity of which has not been adequately studied.

Epidemics of aluminium toxicity causing neurological toxicity are fortunately no longer seen in contemporary haemodialysis practice, and less severe toxicities such as anemia and aluminum-related bone disease appear to be decreasing with time in centres where it is being looked for. The relative contribution of aluminium binders to aluminium toxicity would appear to be minor based on the available evidence.

Newer phosphate binders, such as sevelamer and lanthanum, are limited by both lack of evidence of benefit in terms of hard clinical end-points (cardiovascular disease, mortality) but also by lack of long-term safety data. Lanthanum accumulation has been well documented in patients taking lanthanum carbonate,[30,31] although the long-term effects on patient safety are uncertain. Likewise, such safety data for aluminium binders and even calcium binders are lacking. Indeed, there are no head-to-head trials of different phosphate binders comparing their safety, efficacy (especially with respect to patient-level outcomes) and cost-effectiveness. Contemporary guidelines however, would tend to promote the newer, more costly agents. The onus is on the nephrology community to perform trials to establish high level evidence relating to all aspects of management of hyperphosphatemia including the benefits of lowering serum phosphate per se, as well as questions relating to specific agents and the associated health economic considerations. Moreover large trials which are adequately designed to answer these important questions, should consider all available phosphate binders, including aluminium.

The utility of safety standards of routine water testing for aluminium and monitoring of serum aluminium levels for patients on oral aluminium-based phosphate binders, as well as the avoidance of oral citrate in patients taking aluminium, could reasonably be tested in a prospective, randomised trial, and provides a tantalising opportunity for a potentially significant cost-saving for dialysis patients if the safety of aluminium as a binder could be established.

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