Evolution of renal injury in a chronic model of IgA immune-complex-associated nephropathy

BACKGROUND.: IgA nephropathy (IgAN) is characterized by intense and diffuseIgA mesangial deposits, a variety of histopathological changesand unpredictable clinical course. To elucidate the cause ofthe discrepancy between the unvariable IgA deposition and thehistological picture, we examined the short- and long-term influenceof glomerular IgA immune complexes (IgA-IC) on the progressionof renal lesions in experimental IgAN. METHODS.: IgA-IC renal deposits were induced by sequential administrationof IgA anti-phosphorylcholine and pneumococcal C polysaccharide.Mice treated every other day by three injections (groups A)or nine injections (groups B) were sacrificed 24 h and 1, 4,or 8 weeks (groups 1–4) after cessation of treatment. RESULTS.: Group A1 showed segmental glomerular necrosis and thrombosis.Lesions then converted to segmental mesangial proliferation(A2), more pronounced in A3 and minimal in A4. Group B1 showedsevere proliferative glomerulonephritis and segmental necrosis.The pattern altered to mesangial expansion with glomerular/interstitialinfiltration in B2, milder features in B3 and residual mesangialproliferation in B4. Proteinuria increased progressively duringtreatment reaching its maximum in group B1, but it returnedto near normal levels in group B4. The development of proteinuriaparalleled glomerular/interstitial T cell infiltration. CONCLUSIONS.: These findings demonstrate that renal histopathological alterationsobserved in experimental IgA nephropathy are sustainable onlyby continuous deposition of nephritogenic IgA-IC.