A Contemporary View On Immunoglobulin A Nephropathy: A Literature Review

Abstract

Immunoglobulin​‍​‌‍​‍‌​‍​‌‍​‍‌ A nephropathy (IgAN) is a primary glomerulonephritis that affects the kidney mainly, and it is the leading cause of chronic kidney disease worldwide. Its pathogenesis is best illustrated by the multi-hit model, which starts with the overproduction of galactose-deficient IgA1 (Gd-IgA1), continues with the production of anti-glycan autoantibodies, the formation of pathogenic immune complexes, and their mesangial deposition. These processes lead to the activation of inflammatory and complement pathways, which cause glomerular injury and the progression of fibrosis. 

From the clinical point of view, IgAN shows hematuria, proteinuria, and disease severity varying from case to case. To confirm the diagnosis, a kidney biopsy is necessary, and the Oxford Classification represents a standardized system for evaluating the histopathologic features and forecasting the results. The most important prognostic features are, on one hand, continuous proteinuria, decreased eGFR, and hypertension. 

The treatment originally was only supportive, e.g., with RAAS blockade, but it has been diversified by the addition of new therapies such as SGLT2 inhibitors, sparsentan, and targeted-release budesonide. Next-generation agents, like complement inhibitors and B-cell/BAFF/APRIL–targeted drugs, are on the horizon and can provide a highly personalized medicine approach. However, a lot of work still needs to be done to find dependable biomarkers and fathom patient-specific disease variability despite these achievements. 

The present review consolidates leading evidence regarding IgAN epidemiology, pathogenesis, clinical presentation, and treatment and emphasizes that exploring next steps essential for early diagnostic improvement and thus, the prevention of progression to the final stage of the kidney ​‍​‌‍​‍‌​‍​‌‍​‍‌disease.