Observations on the early renal uptake and later tubular metabolism of radiolabelled aprotinin (Trasylol) in man: theoretical and practical considerations

Abstract

1. The novel method recently developed to measure renal tubular degradation of filtered proteins in man using radiolabelled aprotinin (Trasylol) has been modified to allow the fate and the significance of the renal catabolism of radiolabelled aprotinin to be determined beyond 24 h. 2. Ten renal patients with normal kidney function and variable proteinuria each received two separate intravenous injections of radiolabelled aprotinin, 5.0 mg of 99mTc-labelled aprotinin (40 MBq) and 0.5 mg of 131I-labelled aprotinin (5 MBq). Chromatography (Sephadex-G-25-M) was used to separate undegraded radiolabelled aprotinin from the free isotope in urine and plasma. Renal uptake from σ-camera images (24 h for 99mTc-Iabelled aprotinin and up to 96 h for 131I-labelled aprotinin) and urinary activity (48 and 96 h, respectively) were measured. 3. The renal handling of radiolabelled aprotinin was similar with the two isotopes. Chromatography showed that all plasma activity was undegraded radiolabelled aprotinin, and urine activity was only the free isotopic label. 4. Kidney uptake of 131I-labelled aprotinin was prompt, reaching a cumulative maximum of 37.1 ± 3.0% of dose at 24 h, but falling exponentially thereafter to 5.6 ± 1.0% of dose at 96 h. 5. The rate of excretion of the free label in urine, i.e. the metabolic rate of radiolabelled aprotinin, was relatively constant over the first 24 h (1.6 ± 0.09% of dose/h), but then fell in parallel with the diminishing activity over the kidney, i.e. to 1.0 ± 0.1% of dose/h over 24–48 h and to only 0.4 ± 0.08% of dose/h over 72–96 h. 6. Fractional renal degradation of radiolabelled aprotinin, derived from the mean rate of urinary excretion of the free isotope over a given interval divided by the mean cumulative kidney uptake over the same interval (h−1), fell steeply early and then more slowly to 0.05 ± 0.003 h−1 at 14.25h, and stabilized thereafter varying little between 0.04 ± 0.01 h−1 and 0.05 ± 0.01 h−1 over 36–84 h. 7. Thus, the maximum cumulative kidney uptake of radiolabelled aprotinin is achieved by 24 h, when the metabolic rate and fractional degradation are reliable indices of catabolism. The falling metabolic rate after 24 h, together with the constant rate of fractional degradation, suggests that there is a readily saturable step in the metabolic process. Hence, duplicate measurements of radiolabelled aprotinin uptake and metabolism around 24 h only (12–36 h) are sufficient and offer a simple and a reliable tool in clinical studies for determining the link between renal tubular protein degradation and renal disease progression.