Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy

Andrea Remuzzi, Elena Perticucci, Piero Ruggenenti, Lidia Mosconi, Marcello Limonta, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy. Clearances of uncharged dextrans of broad size distribution were used to evaluate the effects of a 30 day course of enalapril on glomerular barrier function in 10 patients with IgA nephropathy and proteinuria (from 1.4 to 5.6 g/day). Dextran clearance experiments were repeated three times: before enalapril therapy, after 30 days of enalapril and again 30 days after enalapril withdrawal. GFR, but not RPF, was significantly reduced by enalapril (basal 38.3 ± 11.9, enalapril 30.2 ± 12.6 ml/min/1.73 m2) and returned to basal values after enalapril withdrawal. Urinary protein excretion and fractional clearance of albumin were both significantly reduced by enalapril (basal 2.3 ± 1.1 g/day and 102 ± 90 x 10-5, enalapril 1.2 ± 0.6 g/day and 51 ± 23 x 10-5, respectively) and returned to basal values after enalapril withdrawal. Transglomerular passage of large dextrans (radii 54 to 62 Å), but not of lower size (26 to 42 Å) were significantly lowered by enalapril. When enalapril was withdrawn the dextran-sieving profile returned comparable to the baseline levels. A theoretical analysis of dextran-sieving profiles indicated that enalapril lowered the radius of largest membrane pores. This effect was independent from glomerular hemodynamic changes. We conclude that angiotensin converting enzyme inhibitors (CEI) in humans with IgA nephropathy reduces urinary protein excretion by a primary action on the intrinsic glomerular membrane properties enhancing barrier size-selective function. The hypofiltration associated with enalapril therapy in these patients, which was eliminated by its withdrawal, has to be taken into account as a possible undesired effect of CEI in long-term treatment.

Original languageEnglish
Pages (from-to)1267-1273
Number of pages7
JournalKidney International
Volume39
Issue number6
Publication statusPublished - Jun 1991

ASJC Scopus subject areas

  • Nephrology

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