RENAL TUBULAR PROTEIN-DEGRADATION OF RADIOLABELED APROTININ (TRASYLOL) IN PATIENTS WITH CHRONIC-RENAL-FAILURE

1. The new method developed to measure renal tubular degradation of sm all filtered proteins in patients with normal renal function, using ra diolabelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H . R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289-94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either Tc-99m (40 MBq) or I-131 (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. Cr- 51-EDTA clearance (corrected for height and weight) was 40+/-5.4 (rang e 11.2-81) ml min-1 1.73 m-2. Activity in plasma and urine was measure d over 24-48 h, and chromatography on Sephadex-G-25-M was used to sepa rate labelled aprotinin from free (TcO4-)-Tc-99m or I-131. Renal uptak e was measured for Tc-99m-labelled aprotinin only. 3. The volume of di stribution was 20.2+/-2.3 litres. Chromatography showed all plasma act ivity as undegraded aprotinin, and urine activity only as the free lab els (TcO4-)-Tc-99m or I-131). 4. As in patients with normal renal func tion, activity in the kidney appeared promptly, with 5.7+/-2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4+/-1.6% of d ose after 1.5 h, then more slowly to 15.0+/-0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1+/-2.8% of dose at 24 h. Ex tra-renal uptake was again insignificant, and both (TcO4-)-Tc-99m and I-131- appeared promptly in the urine, with similar and uniform rates of excretion over 24h. 5. Both tubular uptake at 24h and the rate of t ubular metabolism over 24h were lower than in the patients with normal renal function studied previously, but only the rate of tubular metab olism was directly related to the glomerular filtration rate (r=0.75, P < 0.02). 6. Correction for the reduced glomerular filtration rate yi elded values for both tubular uptake (0.67+/-0.14 versus 0.32+/-0.03% of dose/ml of glomerular filtration rate, P<0.005), and tubular metabo lism (0.033+/-0.07 versus 0.015+/-0.00.1% of dose h-1 ml-1 of glomerul ar filtration rate, P<0.005) that were higher by comparison with those for patients with normal renal function studied previously. 7. Fracti onal renal degradation of Tc-99m-aprotinin (in h-1), derived from the mean rate of urinary excretion of the free isotope over a given interv al, divided by the mean cumulative kidney uptake over the same interva l, also fell steeply early, and then more slowly to 0.07+/-0.01 h-1 at 14.25 h (between 4.5 and 24 h). 8. It is concluded that the method de scribed previously is also suitable in patients with chronic renal fai lure, allowing further research into renal disease progression.