ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome

Patients with idiopathic membranous nephropathy (IMN) and persistent nephrotic-range proteinuria are at risk for progression to end-stage renal failure. Whether angiotensin-converting enzyme (ACE) inhibitors are also renoprotective in these patients remains elusive. In 14 patients with IMN (patients) and persistent proteinuria (protein > 3 g/24 h for >6 months), we studied mean arterial pressure (MAP), urinary protein excretion, glomerular filtration rate (GFR), renal plasma flow (RPF), and albumin and neutral dextran fractional clearance after 2 months washout from previous antihypertensive treatment (basal), after 2 months of enalapril (2.5 to 20 mg/d) therapy (posttreatment), and 2 months after enalapril withdrawal (recovery). MAP, proteinuria, and GFR were also measured at the same time points in 6 patients with IMN and persistent overt proteinuria maintained on conventional treatment throughout the study period (controls). Basal MAP, proteinuria, and GFR were similar in the two study groups. However, in patients at the end of the treatment period, MAP (posttreatment, 99.6 ± 11.2 versus basal, 103.3 ± 12.1 mm Hg; P <0.05), proteinuria (posttreatment protein, 5.0 ± 2.9 versus basal, 7.1 ± 4.9 g/24 h; P <0.05), albumin fractional clearance (posttreatment median, 1.7 x 10^-3; range; 0.2 to 22.7 x 10^-3 versus basal median, 4.1 x 10^-3; range, 0.4 to 22.1 x 10^-3; P <0.05), and fractional clearance of largest neutral dextrans (radii from 62 to 66 Å) were significantly less than basal values. At recovery, MAP significantly increased to 106.6 ± 11.7 mm Hg (P <0.001 versus enalapril), but all other parameters remained less than basal values. GFR and RPF were similar at each evaluation. Changes in proteinuria after treatment withdrawal positively correlated (r= 0.72; P <0.01) with baseline GFR. Theoretical analysis of dextransieving data indicated that ACE inhibitor treatment significantly improved glomerular membrane size-selective dysfunction. This effect persisted more than 2 months after treatment withdrawal. No patient had symptomatic hypotension, acute renal function deterioration, or hyperkalemia during enalapril treatment. Thus, in patients with IMN and long- term nephrotic syndrome, ACE inhibitor treatment, but not conventional therapy, improves glomerular barrier size selectivity. The antiproteinuric effect of ACE inhibition is long lasting, especially in patients with more severe renal insufficiency. This is the premise of a long-term renoprotective effect that may limit the need for treatment with more toxic drugs. (C) 2000 by the National Kidney Foundation, Inc.