1. Progression to renal failure may be linked to the degree of proteinuria through tubulo-interstitial mechanisms. However, there are no data in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril. We developed a method to allow such studies, and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretion.

2. In this study, 10 patients with mild renal impairment (51Cr-EDTA clearance 63.7 ± 8.3 ml · min−1 · 1.73 m−2) and heavy proteinuria (8.2 ± 2.3 g/24 h) were given lisinopril (10–20 mg) for 6 weeks. Renal tubular catabolism of intravenous aprotinin was measured before and after lisinopril by renal imaging and urinary excretion of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Fresh timed urine collections were also analysed for ammonia excretion every fortnight from 6 weeks before treatment. Total urinary N-acetyl-β-d-glucosaminidase and the more tubulo-specific N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme were also measured.

3. After lisinopril proteinuria fell significantly as expected (from 9.5 ± 1.6 to 4.5 ± 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism over 26 h (from 1.7 ± 0.1 to 1.2 ± 0.1% dose/h, P < 0.01) and in fractional degradation of aprotinin (from 0.08 ± 0.02 to 0.04 ± 0.007/h, P < 0.04). Ammonia excretion also fell significantly (from 1.2 ± 0.1 to 0.6 ± 0.1 mmol/h, P < 0.0001), as did both total urinary N-acetyl-β-d-glucosaminidase (P < 0.0001) and the N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme (P < 0.015). These observations after lisinopril treatment have not been described previously. There was no significant change in blood pressure nor in glomerular haemodynamics.

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