Searching for uremic toxins

Abstract

Treatment of uremia by hemodialysis has become widespread over the last 40 years and has improved substantially over that time. However, people treated with this modality continue to suffer from multiple disabilities. Retention of organic solutes, especially those poorly removed by hemodialysis, likely contributes to these disabilities. Certain classes of solutes are removed less well than urea by hemodialysis and by the normal kidney. These include protein-bound solutes, relatively large solutes, sequestered compounds, and substances removed at rates higher than urea by the normal kidney. Several strategies could be used to discover the solutes responsible for residual morbidities in standardly dialyzed people. Rather than continue to focus only on urea removal as an index for dialysis adequacy, finding additional approaches for removing toxic solutes with characteristics different from urea (and the similar small solutes it represents) is a desirable and feasible goal.

Figures

Figure 1.

Time-averaged plasma solute levels in patients undergoing conventional thrice-weekly hemodialysis. Uremic solutes that are relatively large compared to urea are poorly cleared by even high flux dialyzers. The increase in the level of p-cresol sulfate would be of even greater magnitude if free rather than total plasma solutes levels were compared.