Immunopathological predictors of prognosis in IgA nephropathy

IgA nephropathy (IgAN) is characterized by the expansion of the glomerular mesangial matrix with mesangial cell proliferation and/or mononuclear cell infiltration. Glomeruli typically contain generalized diffuse granular mesangial deposits of IgA (mainly galactose-deficient polymeric IgA1), IgG and C3. Electron-dense deposits are observed in the glomerular mesangial area and glomerular basement membrane. Therefore, this disease is considered to be an immune complex-mediated glomerulonephritis. The detailed observations of electron-dense deposits are of value for the evaluation of the disease activity. The evidence- and lumped-system-based histological classification can identify the magnitude of the risk of disease progression and is useful for predicting long-term renal outcome in this disease. A study of IgAN patients showed that the number of angiotensin-II-positive cells was correlated with mast cells containing both tryptase and chymase and containing only tryptase in the interstitial lesions with the most severe pathological changes. Hypercomplementemia occurs in the progression of IgAN and is controlled by an increase of complement regulatory proteins. The measurement of urinary levels of membrane attack complex and factor H and extraglomerular C3 deposition could be useful indicators of renal injury in patients with IgAN. Development of glomerulosclerosis in IgAN patients is associated with podocytopenia and the alteration of the podocyte components, i.e. podocalyxin and dendrin. It appears that the number of urinary podocytes and levels of urinary podocalyxin are useful for predicting histological changes in IgAN patients. A positive correlation was observed between acute extracapillary changes and the number of dendrin-positive nuclei per glomerulus in patients with IgAN. It is concluded that there are many immunopathological predictors of prognosis, including genetic background, in this disease. Thus, the early diagnostic screening of prognosis predictors and subsequent intervention are important for the good prognosis in this disease.