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C5b-9 glomerular deposition and tubular α3β1-integrin expression are implicated in the development of chronic lesions and predict renal function outcome in immunoglobulin A nephropathy

Objective. Tubular atrophy is one of the factors predicting poor outcome of renal function in primary immunoglobulin A nephropathy (IgAN). However, the development of tubular atrophy is a late phenomenon during the disease progression. It would be useful to identify early factors that potentially result in renal damage and could be used as early predictors of renal outcome. Material and methods. Forty-eight patients with IgAN were examined retrospectively. All patients had a renal biopsy at the beginning of the study. Histological parameters were reviewed and immunohistochemistry was performed on cryostat sections. Monoclonal antibodies used were against C5b-9, α3β1-integrin, transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA), and the results were correlated with histological data and long-term outcome of renal function. Results. In the glomeruli the extent of C5b-9 deposition had significant positive correlations with the degree of focal glomerulosclerosis (p=0.005), tubular atrophy (p=0.003), interstitial inflammation (p=0.005) and tubular expression of α3β1 (p=0.0001). α3β1 tubular expression correlated positively with the severity of proteinuria (p=0.01), number of glomerular and tubulointerstitial myofibroblasts, and the degree of tubular atrophy (p=0.0001) and interstitial monocyte infiltration (p=0.005). Tubular α3β1 expression and the degree of tubular atrophy had significant implications in the development of renal failure at the beginning and at the end of follow-up, respectively. Conclusions. Glomerular deposition of C5b-9 may participate in the development of glomerulosclerosis in IgAN. Furthermore, its positive correlation with the intensity of tubular α3β1-integrin suggests a possible implication in the development of tubulointerstitial fibrosis.