More than 100,000 patients now receive chronic hemodialysis therapy in Medicare's End Stage Renal Disease Program. Hemodialysis related amyloidosis affects a significant portion of these patients. The syndrome presents clinically as carped tunnel syndrome, cystic bone lesions, and arthropathies. The disorder has been identified with excessive circulating and stored quantities of Beta2-microglobulin (Beta2-M). The syndrome cannot be cured, only prevented. This Phase I proposal describes experiments to identify and characterize sorbent materials which can be used in conjunction with the patients' normal dialysis treatment to reduce body burdens of Beta2-M. Phase II aims will be to establish flow and sorbent volume criteria for the reduction of Beta2-M in conjunction with normal hemodialysis. In Phase III clinical trials, mass balances in the clinical setting will be used to project whether significant clinical benefits will accrue to the dialysis patients. Clinically significant reduction of Beta2-M at an affordable cost is the long term aim of this program. Based on daily generation rates, estimates at 200 mg/70 kg patient, required sorbent capabilities of 200- 300 mg Beta2-M/dialysis are projected. Such reduction, augmenting Beta2- M removal by high flux dialyzers, should provide a measurable benefit to this patient population.
