Clearance and synthesis rates of beta 2-microglobulin in patients undergoing hemodialysis and in normal subjects.

Retention of beta 2-microglobulin in patients undergoing hemodialysis is associated with a beta 2-microglobulin-derived amyloidosis. Removal of beta 2-microglobulin by renal replacement therapy has been proposed for the prevention of this amyloidosis. Currently, however, data on the beta 2-microglobulin synthesis rate in patients undergoing hemodialysis are scarce, and consequently it remains speculative how much removal would be necessary to counterbalance synthesis. The plasma kinetics of iodine 131-labeled beta 2-microglobulin were therefore examined in 11 patients with anuria who were undergoing long-term hemodialysis. Five healthy persons served as controls. Kinetic modeling of the plasma curves showed that the data fitted a two-pool model (r2 greater than 0.96) consisting of a rapid 2 to 4 hour distribution phase followed by a less steep curve, described by the plasma (metabolic) clearance (Clp). Synthetic rates were calculated from Clp and the beta 2-microglobulin steady state plasma concentration (plus beta 2-microglobulin removal during hemodialysis in the case of high flux hemodialysis). The results showed a significantly higher Clp in normal controls as compared with patients undergoing hemodialysis (65.5 +/- 12.8 ml/min (mean +/- SD) versus 3.4 +/- 0.7 ml/min). In contrast, the beta 2-microglobulin synthesis rate in the patient group (3.10 +/- 0.79 mg/kg/day) was not significantly different from that of normal controls (2.40 +/- 0.67 mg/kg/day), which was due to markedly elevated beta 2-microglobulin plasma concentrations in the patients (37.6 +/- 14.1 mg/L vs 1.92 +/- 0.27 mg/L). These findings suggest that the presence of end-stage renal disease does not have a significant impact on the beta 2-microglobulin generation rate. The degree of accumulation of beta 2-microglobulin in patients undergoing hemodialysis seems to depend on the loss of renal excretory function.