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The kinetics of beta 2-microglobulin (beta 2m) were studied in five anephric or anuric hemodialysis patients. Human beta 2m was isolated from peritoneal dialysate using ion-exchange and gel chromatography and radiolabeled with 125I. Patients were injected with 10 microCi labeled beta 2m. In one study (N = 4), plasma activity was measured over 72 hours. In a second study (N = 4), patients received low-flux dialysis 24 hours after injection and high-clearance dialysis (Bellco BL655) at 48 hours. Plasma activities were fitted to a three-compartment, variable volume model. Endogenous beta 2m levels (radioimmunoassay) were 56 +/- 6 mg/liter. The beta 2m distribution volume was 12.7 +/- 2.0 liter (0.20 +/- 0.03 liter/kg) and the non-renal clearance was 3.0 +/- 0.4 ml/min. The generation rate, 9.9 +/- 1.7 mg/hr (0.16 +/- 0.04 mg/kg/hr), was similar to that measured in subjects with normal renal function. The three compartment model derived from the turnover data gave an adequate fit of the arterial concentrations of endogenous and exogenous beta 2m during low-flux (nil beta 2m clearance) and high-clearance (beta 2m clearance of 19 ml/min) dialysis. Simulations based on this model indicate that extracorporeal treatment can at best remove about 50% of weekly production. These results suggest that beta 2m production is not increased in dialysis patients, that there is substantial non-renal beta 2m clearance, and that the amount of beta 2m that can be removed by extracorporeal therapy is therefore limited.