PROXIMAL RENAL TUBULAR PEPTIDE CATABOLISM, AMMONIA EXCRETION AND TUBULAR INJURY IN PATIENTS WITH PROTEINURIA - BEFORE AND AFTER LISINOPRIL

1. Progression to renal failure may be linked to the degree of protein uria through tubulo-interstitial mechanisms. Non ever, there are no da ta in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril, We develope d a method to allow such studies, and found increased tubular cataboli sm of Tc-99m-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretio n. 2. In this study, 10 patients with mild renal impairment (Cr-51-EDT A clearance 63.7 +/- 8.3 ml.min(-1) 1.73 m(-2)) and heavy proteinuria (8.2 +/- 42.3 g/24 h) were given lisinopril (10-20 mg) for 6 weeks. Re nal tubular catabolism of intravenous aprotinin was measured before an d 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 ex cretion every fortnight from 6 weeks before treatment. Total urinary N -acetyl-beta-D-glucosaminidase and the more tubulo-specific N-acetyl-b eta-D-glucosaminidase 'A2' isoenzyme were also measured. 3. After lisi nopril proteinuria fell significantly as expected (from 9.5 +/- 1.6 to 3.5 +/- 1.0 g/24 h, P < 0.01). This was associated with a reduction i n metabolism over 26h (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 tot al urinary N-acetyl-beta-D-glucosaminidase (P < 0.0001) and the N-acet yl-beta-D-glucosaminidase 'A2' isoenzyme (P < 0.015), These observatio ns after lisinopril treatment have not been described previously. Ther e was no significant change in blood pressure nor in glomerular haemod ynamics.