Monitoring Immune Responses in IgA Nephropathy: Biomarkers to Guide Management.

Abstract

IgA nephropathy (IgAN) is the commonest biopsy-reported primary glomerulonephritis worldwide. It has an incidence which peaks among young adults, and 30 to 40% of patients’ progress to end stage kidney disease within twenty years of diagnosis. Ten-year kidney survival rates have been reported to be as low as 35% in some parts of the world. The successful management of IgAN is limited by an incomplete understanding of the pathophysiology of IgAN and a poor understanding of how pathophysiology may vary both from patient to patient and between patient groups, particularly across races. This is compounded by a lack of rigorously designed and delivered clinical trials in IgAN. This is slowly changing, with a number of Phase 2 and 3 clinical trials of novel therapies targeting a number of different putative pathogenic pathways in IgAN due to report in the next 5 years. From our current, albeit limited, understanding of the pathophysiology of IgAN it is unlikely a single therapy will be effective in all patients with IgAN. The successful management of IgAN in the future is, therefore, likely to be reliant on targeted therapies, carefully selected based on an individualized understanding of a patient’s risk of progression and underlying pathophysiology. The potential role of biomarkers to facilitate personalization of prognostication and treatment of IgAN is immense. Here we review the progress made over the past decade in identifying and validating new biomarkers, with a particular focus on those that reflect immunological responses in IgAN.