BETA-2-MICROGLOBULIN METABOLISM IN UREMIC PATIENTS WHO ARE UNDERGOINGDIALYSIS

Plasma beta 2-microglobulin (beta2m) is increased in chronically hemod ialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We u ndertook metabolic studies to define whether plasma beta2m is regulate d by extrarenal proteolysis of the protein or by storage in a captatio n pool, a condition which may precede beta2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy contr ols were enrolled into the 6 to 10 day study. Using trace amounts of I -131-beta2m and total body counting, half-life was between 2.4 and 8 d ays. I-125-beta2M plasma kinetics was more suitable to calculate fract ional catabolic rate and synthetic rate. A three compartment model was chosen to calculate turnover parameters in dialysis patients, whereas the regular two compartment model fitted best for healthy controls. B eta2m synthesis rate was increased in uremic patients when compared wi th controls (4.49 +/- 2.60 vs. 3.68 +/- 1.43 mg/kg/day, NS). The three compartment model did not integrate all the experimental data, since it was possible to calculate a captation compartment which accumulated beta2m without fast proteolysis. The captation pool was positively co rrelated with plasma beta2m concentration and comprised between 23% an d 59% of the amount of the beta2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta2m indicate a s light increase in beta2M synthesis rate in uremic patients on supporti ve therapy, irrespective of the technique in use. Kinetic analysis req uires a model taking into account a storage compartment which is more complex than the three compartment model. Only synthetic membranes are able to remove beta2m by filtration and/or adsorption, in order to le ssen beta2m burden and to postpone dialysis amyloidosis.