Transcapillary escape rate of (125)I-albumin in relation to timing of blood sampling: the need for standardization

BACKGROUND: Increased vascular permeability is an early sign of vascular damage and can be measured with the transcapillary escape rate of albumin (TER(alb)). Although TER(alb) has a multi-exponential kinetic model, most published TER(alb) data are based on mono-exponential kinetic models with variation in blood sampling schemes. Aim of this posthoc study was to evaluate the influence of variation in blood sampling schemes and the impact of mono- or bi-exponential analyses on the calculation of TER(alb). Study participants were part of a cross-over intervention study protocol, investigating effects of sodium loading on blood pressure, endothelial surface layer and microcirculation. Multiple blood samples were drawn between 3 and 60 min after injection of radioactive iodide labeled human serum albumin (rHSA). RESULTS: In total 27 male participants with 54 measurements were included. For all participants the maximum serum radioactivity was reached within 20 min, while 85% of the participants had their maximum serum activity within 10 min. The TER(alb) calculated with the subsequently chosen T(20–60 min) reference scheme (6.19 ± 0.49%/h) was significantly lower compared to the TER(alb) of the T(3–60 min), T(5–60 min), and T(max – 60 min) schemes. There was no significant difference between the T(20–60 min) reference scheme and the T(10–60 min) and T(15–60 min) schemes. Bi-exponential kinetic modeling did not result in significant different observations compared to the mono-exponential kinetic analysis. CONCLUSIONS: As there is variation in the timing of the maximum serum radioactivity of rHSA, blood sampling schemes starting before 10 min after administration of rHSA will result in a significant overestimation of TER(alb). In addition, variation in kinetic modeling did not result in significant changes in TER(alb). Therefore, we emphasize the need to standardize TER(alb) and for practical and logistical reasons advocate the use of a mono-exponential model with blood sampling starting 20 min after rHSA administration.