The Pathology of IgA Nephropathy: How Can It Inform Management?

IgA nephropathy (IgAN), the world's most common form of primary glomerulonephritis (GN), has a variable clinical and pathologic presentation. While all cases of IgAN show dominant or codominant glomerular IgA deposits, their histologic appearance can range from essentially normal to severe crescentic GN. Oxford (MEST-C) scoring is widely used to classify IgAN on kidney biopsies and has been validated to correlate with clinical presentation and as an independent predictor of kidney outcomes in multiple studies. Components of MEST-C, most notably endocapillary hypercellularity (E score) and crescents (C score), have also been shown to correlate with response to immunosuppressive therapy. Furthermore, immunohistologic evidence of complement activation by the alternative pathway and sometimes the lectin pathway correlates with histologic lesions, proteinuria, and kidney survival, suggesting the complement cascade as a potential therapeutic target. Recent clinical trials have demonstrated the potential of newer classes of immunosuppressive agents as well as complement inhibitors to reduce proteinuria, a marker associated with disease progression, in patients with IgAN. While pathologic studies of kidney biopsies have generally not been part of these trials, this review presents an algorithm by which kidney biopsy findings can be used to guide the choice of therapeutic agents in patients with IgAN.