A new method to measure renal tubular degradation of small filtered proteins in man using radiolabelled 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 ^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.