CATIONIC DEXTRAN INDUCES MESANGIOPROLIFERATIVE NEPHRITIS IN RATS INDEPENDENT OF GLOMERULAR IGA DEPOSITION

Background. Dextran-induced mesangioproliferative glomerulonephritis i n mice and, as recently reported. in rats is used as a model of IEA ne phropathy. The pathogenetic role of the glomerular IgA deposits in thi s model, however, is unclear since IgG is often deposited in parallel. Methods. Lewis rats were immunized with cationic DEAE-dextran. Follow ing this, rats received 5 x/week i.v. injections of 3 mg DEAE-dextran each, from days 20 to 80 and were then followed until day 120. Results . Rats developed transient proteinuria (range 63-152 mg/24 h) and haem aturia on day 80, Renal biopsies obtained at days 60, 80, 100 and 120 showed mild to severe mesangioproliferative changes at days 80 and 100 which did not persist at day 120. Electronmicroscopy revealed mesangi al immune deposits, signs of endothelial activation and vacuoles in me sangial cells and podocytes. Compared to normal, age-matched controls, in the nephritic rats significant (P<0.05) increases were noted for g lomerular total cellularity, alpha-smooth-muscle actin expression (a m arker of activated mesangial cells), monocyte/macrophage counts, and m atrix proteins. Using three different antibodies, no evidence of glome rular IgA deposition was detected at any time point. In contrast, glom erular IgG, IgM, C3, and occasional small C5b-9 deposits were present in nephritic rats. Circulating IgG but not IEA anti-dextran antibodies could be demonstrated in nephritic rats. Conclusions. The data confir m that mesangioproliferative glomerulonephritis can be induced in rats by immunization and chronic challenge with cationic dextran, Our data also show that in rats glomerular IgG deposition rather than IgA, app ears to play an important pathogenetic role in this mesangioproliferat ive glomerulonephritis model.