THE INFLUENCE OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ON RENAL TUBULAR FUNCTION IN PROGRESSIVE CHRONIC NEPHROPATHY

The influence of angiotensin-converting enzyme (ACE) inhibition on ren al tubular function in progressive chronic nephropathy was investigate d in 69 patients by the lithium clearance (C-Li) method. Studies were done repeatedly for up to 2 years during a controlled trial on the eff ect of enalapril an progression of renal failure, The pattern of prote inuria was followed over the first 9 months. At baseline, the glomerul ar filtration rate (GFR) was 5 to 68 mL/ min. Absolute proximal tubula r reabsorption rate of fluid (APR), estimated as the difference betwee n GFR and C-Li, was 1 to 54 mL/min. Calculated fractional proximal rea bsorption (FPR) was moderately subnormal, During the study, GFR decrea sed and sodium clearance was unchanged; fractional excretion of sodium therefore increased, In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C-Li was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly; and potassium clearance was significantly decreased. T hrough the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients r andomized to treatment with conventional antihypertensive drugs (n = 3 5), C-Li was unchanged until severe reduction in GFR, APR and FPR decr eased gradually, and potassium clearance was almost unchanged, These d ifferences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treat ment regimen was associated with a long-term slower progression of ren al failure, Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearanc es of immunoglobulin G and retinol-binding protein were unchanged in t his group. in the conventional group, the fractional clearances of the se three plasma proteins all increased, it is concluded that in progre ssive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, a nd protein compared with conventional antihypertensive therapy, During ACE inhibition, the reabsorptive capacity of the proximal tubule appe ared to be better preserved, which might be of importance for the bene ficial effect of this treatment in chronic renal disease. (C) 1996 by the National Kidney Foundation, Inc.