A NEW METHOD TO MEASURE RENAL TUBULAR DEGRADATION OF SMALL FILTERED PROTEINS IN MAN USING RADIOLABELED APROTININ (TRASYLOL)

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 Tc-99m (40 MBq) or I-131 (I 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 Tc-99mO4- or I-131-. Renal uptake was measured for Tc-99m-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 (Tc-99mO4- or I-131-). 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 Tc-99mO4- and I-131- 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 Tc-99m and I-131, respectively). 6. Fractional renal tubular degradation of Tc-99m-aprotinin (in h-1) is a measure of its turnover value over a given interval and is given by: [GRAPHICS] 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 3h 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.