Validation of a two-pool model for the kinetics of beta2-microglobulin

Secondary amyloidosis due to beta-2-microglobulin (beta2-m) is a serious long-term complication in patients on regular dialysis therapy. Beta2-m can be considered a middle-molecule marker used to facilitate the assessment of dialysis efficacy. For this purpose, a validated model that calculates characteristic efficacy parameters, such as Kt/V, TAC and generation rate, is needed. There is general agreement that beta2-m-kinetics should be described by a two-pool model, but little has been published to validate such an approach. We measured the beta2-m concentration profiles of eight stable patients during hemodialysis (HD) at the start of treatment, after 30 minutes, after 60 minutes, and every hour until the end. Thereafter they were measured at 10-minute intervals for an hour. The dialyser clearances were determined from the plasma concentrations in front of and behind the dialyser twice during each session - after 1 hour, and 4 hours from the start of treatment. The kinetic parameters of a two-pool model (e.g. the compartment volumes V1 and V2, the mass transfer coefficient K12 and the generation rate G) were determined from the optimal fit of the measured concentration profile. The table below summarises the results by giving the mean and standard deviation for each parameter: [table: see text]. Inter-individual differences in V1/V2 and K12 were high, ranging from 2.5 to 10.0 for V/V2 and from 26 to 140 for K12. Error analysis suggested that these wide ranges were due to the method and that in reality the probable range of V is 25-36% of TBW, of V1/V2 3.5-5.3, and of K12 30-80 ml/min. With standard values for these three parameters (V = 30% of TBW, V/V2 = 4.4 and K12 = 55 ml/m), equal for all patients, and their respective ranges, Kt/W can be calculated with a standard deviation of 13%. Kt/W > 1.2 secures the maximum possible beta2-m removal with three HD treatments a week.

The parameters of a two-pool model of beta2-m kinetics can be derived from concentration profiles obtained under routine dialysis conditions, but accuracy is not completely satisfactory. Similar to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2-m) can be calculated from the pre- and post-dialysis concentrations of beta2-m, body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the maximum possible removal of beta2-m in HD with three sessions per week.