What can we learn from the saga of chitosan gums in hyperphosphatemia therapy?

Abstract

Control of high serum phosphorus, a marker of poor outcome, is still a poorly achieved goal in dialysis therapy. Therefore, the 2009 study (Savica et al., J Am Soc Nephrol 20: 639-644, 2009) showing a significant drop of serum phosphate (2.35 mg/dl) after only 2 weeks of chewing a chitosan-containing gum two times per day was received with great hopes by the renal community. Chitosan is a polymer of glucosamine, similar to sevelamer, which allegedly would bind phosphate present in high concentrations in the saliva of renal patients. Recent randomized studies, however, have been unable to duplicate these results. A systematic and detailed quantitative analysis of the available data was performed. It concluded that the amount of chitosan contained in the chewing gum (20 mg) is too little to account for the originally observed reduction in serum phosphate and be of any use as a phosphate binding agent in the management of hyperphosphatemia. It was postulated that the original marked drop in serum phosphate may have been caused by the Hawthorne effect, which is frequently observed in nonrandomized clinical trials. Two important lessons derived from this analysis are emphasized. The first lesson is the demonstration of the importance of randomized, placebo-controlled studies in clinical research. If randomization had been performed in the original study, the Hawthorne effect would have been detected. The second lesson is showing the importance of quantitative analysis, which in this case, would have avoided the time and effort expended in several randomized clinical trials that eventually concluded the ineffectiveness of the chitosan-containing chewing gums as a phosphate binder.