The utility of glomerular C4d immunostaining in renal biopsies in patients with immunoglobulin A nephropathy. A clinicopathological study

The course of IgA nephropathy (IgAN) is highly variable and ranges from a totally benign condition to end-stage renal disease in approximately one third of cases. The identification of new prognostic markers could provide insights into the pathogenesis of IgAN and unveil new therapeutic avenues. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. It is thought that activation of the lectin pathway in IgAN is associated with more severe renal damage, and more severe histological findings. In view of the above, the aim of the present study was to compare the clinical presentation, laboratory data, and histological lesions in the renal biopsy in IgAN patients with positive and negative staining for mesangial C4d depositions. Our study revealed that hypertension, severe proteinuria, a high level of serum creatinine, low eGFR at the time of presentation, as well as tubular atrophy/interstitial fibrosis > 50%, and endocapillary proliferation were significantly more frequent in the C4d (+) group than in the C4d (–) group. Based on our research, we can assume that mesangial immunoexpression of C4d seems to be a useful prognostic factor in IgAN