Angiotensin II local hyperreactivity in the progression of IgA nephropathy

Immunologic and hemodynamic factors are likely to work in synergism in the progression of immunoglobulin A nephropathy (IgAN) toward sclerosis. The local activation of the renin-angiotensin system may be one the most relevant mechanisms. We investigated the hemodynamic effects of the acute administration of angiotensin-converting enzyme inhibitor (ACEI) (captopril 50 mg). The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were measured by 51Cr-EDTA and 125I hippurate clearances. The correspondent filtration fractions (FFs) in basal conditions and after administration of ACEI were calculated, then the changes in FF (delta FF and % delta FF) were determined. We studied 27 IgAN patients. Eighteen patients had normal renal function (GFR, 112 +/- 19 mL/min/1.73 m2) and nine had moderate renal impairment (GFR, 54 +/- 13 mL/min/1.73 m2). Sixteen patients had proteinuria > or = 0.5 g/d. In addition, 12 glomerulonephritis control cases and eight healthy subjects were investigated. After the administration of ACEI in healthy subjects we observed slight modifications in the GFR, a significant increase in the ERPF (P < 0.005), and a significant decrease in FF (P < 0.04). Similarly, in IgAN patients with normal renal function the GFR increased slightly, the ERPF increased significantly (P < 0.01), and there was a decrease in FF (P < 0.01). The delta FF and % delta FF values were not significantly different from those found in the controls. In patients with initial renal failure GFR remained unchanged, ERPF increased significantly (P < 0.005), and FF significantly decreased (P < 0.004). However, the changes in delta FF and % delta FF were significantly greater than those found in healthy controls (P < 0.01) and in IgAN patients with normal renal function (P < 0.001). IgAN patients with proteinuria levels > or = 0.5 g/d showed greater changes in delta FF and % delta FF after the administration of ACEI than patients with proteinuria levels lower than 0.5 g/d (P < 0.003 and P < 0.04, respectively) or proteinuric control cases (P < 0.05 and P < 0.01, respectively). This different response in proteinuric and nonproteinuric patients was evident even when the analysis was limited to the subgroup of IgAN patients with normal renal function. The decrease in FF consequent to an increase in the ERPF after the administration of ACEI suggests a local hyperactivity of the renin-angiotensin system in some cases of IgAN.(ABSTRACT TRUNCATED AT 400 WORDS)