Beta 2-microglobulin metabolism in uremic patients who are undergoing dialysis

Plasma beta 2-microglobulin (beta 2m) is increased in chronically hemodialyzed patients and remains in a steady range once residual diuresis has stopped. Factors controlling such a steady state are unknown. We undertook metabolic studies to define whether plasma beta 2m is regulated by extrarenal proteolysis of the protein or by storage in a captation pool, a condition which may precede beta 2m-derived amyloidogenesis. Seventeen uremic patients on supportive therapy and five healthy controls were enrolled into the 6 to 10 day study. Using trace amounts of 131I-beta 2m and total body counting, half-life was between 2.4 and 8 days. 125I-beta 2m plasma kinetics was more suitable to calculate fractional 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. beta 2m synthesis rate was increased in uremic patients when compared with 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 beta 2m without fast proteolysis. The captation pool was positively correlated with plasma beta 2m concentration and comprised between 23% and 59% of the amount of the beta 2m disappearing from plasma per day. In conclusion, metabolic studies with radioiodinated beta 2m indicate a slight increase in beta 2m synthesis rate in uremic patients on supportive therapy, irrespective of the technique in use. Kinetic analysis requires a model taking into account a storage compartment which is more complex than the three compartment model.(ABSTRACT TRUNCATED AT 250 WORDS)