1. A method has been developed to measure the renal tubular degradation of small filtered proteins in man using radiolabelled aprotinin (Trasylol), a 6500 Da cationic polypeptide.
2. Aprotinin (0.5 or 5.0 mg) was labelled with either 99mTc (40 MBq) or 131I (1 MBq) and injected intravenously in 19 renal patients (10 with normal renal function and nine on haemodialysis). Activity in plasma and urine was measured over 48 h, and chromatography with Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO-4 or 131I-. Renal uptake was measured for 99mTc-labelled aprotinin only.
3. The volumes of distribution were similar in all patients: 18.2 ± 0.4 litres in those with normal renal function and 20.2 ± 0.1 litres in the others. Chromatography showed all plasma activity as undegraded aprotinin and urine activity only as the free labels (99mTcO-4 or 131I-).
4. In patients with normal renal function, activity in the kidneys rose rapidly to 24.2 ± 2.8% of dose after 90 min and to 42.2 ± 3.4% of dose after 24 h. In the dialysis patients, activity over the kidneys was only 2.7 ± 0.8% of dose at 24 h. Extra-renal uptake was insignificant in all patients with normal kidney function.
5. Both 99mTcO-4 and 131I- appeared in the urine promptly after injection, and the rates of excretion of the two isotopes were similar, varying little over 24 h (1.8 ± 0.04% of dose/h and 1.7 ± 0.04% of dose/h for 99mTc and 131I, respectively).
6. Fractional renal tubular degradation of 99mTc-aprotinin (in h−1) is a measure of its turnover value over a given interval and is given by: Mean urinary appearance of free isotope (% of dose/h)/mean cumulative kidney uptake over the same interval (% of dose) The rate of fractional degradation fell rapidly from 0.20 ± 0.02 h−1 between 0 and 90 min to 0.08 ± 0.01 h−1 between 90 min and 3 h to 0.07 ± 0.01 h−1 between 3 and 4.5 h and to 0.05 ± 0.002 h−1 between 4.5 and 24 h.
7. The stability of urinary excretion of free isotope during the 24 h after injection, together with the relative stability of fractional degradation after 4.5 h, and the reproducibility of the technique offer a practical method for the further study of filtered protein catabolism by the renal tubules in man. This has hitherto not been possible.