EVOLUTION OF RENAL INJURY IN A CHRONIC MODEL OF IGA IMMUNE-COMPLEX ASSOCIATED NEPHROPATHY

Background. IgA nephropathy (IgAN) is characterized by intense and dif fuse IgA mesangial deposits, a variety of histopathological changes an d unpredictable clinical course. To elucidate the cause of the discrep ancy between the unvariable IgA deposition and the histological pictur e, we examined the short- and long-term influence of glomerular IgA im mune complexes (IgA-IC) on the progression of renal lesions in experim ental IgAN. Methods. IgA-IC renal deposits were induced by sequential administration of IgA anti-phosphorylcholine and pneumococcal C polysa ccharide. Mice treated every other day by three injections (groups A) or nine injections (groups B) were sacrificed 24 h and 1, 4, or 8 week s (groups 1-4) after cessation of treatment.Results. Group A1 showed s egmental glomerular necrosis and thrombosis. Lesions then converted to segmental mesangial proliferation (A2), more pronounced in A3 and min imal in A4. Group B1 showed severe proliferative glomerulonephritis an d segmental necrosis. The pattern altered to mesangial expansion with glomerular/interstitial infiltration in B2, milder features in B3 and residual mesangial proliferation in B4. Proteinuria increased progress ively during treatment reaching its maximum in group B1, but it return ed to near normal levels in group B4. The development of proteinuria p aralleled glomerular/interstitial T cell infiltration. Conclusions. Th ese findings demonstrate that renal histopathological alterations obse rved in experimental IgA nephropathy are sustainable only by continuou s deposition of nephritogenic IgA-IC.