Immunoglobulin A nephropathy: pathogenesis, diagnosis and treatment

Immunoglobulin A nephropathy (IgAN) is classified as an autoimmune disease.It is characterized by the formation of IgA1-containing immune complexes and their deposition in mesangial cells.This process triggers glomerular inflammation and leads to progressive fibrosis of the kidney.IgAN is recognized as one of the most common primary glomerulonephritis worldwide and leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD).Its pathogenesis includes a multihit process beginning with mucosal immune dysregulation leading to the overproduction of galactose-deficient IgA1 (Gd-IgA1), the formation of anti-Gd-IgA1 autoantibodies, immune complex deposition, and complement activation through the alternative and lectin pathways.Diagnosis requires kidney biopsy, supported by Oxford MEST-C classification to assess prognosis.Clinical and other tests, such as serum IgA and imaging, remain supportive but nonspecific.Treatment includes optimal supportive care as first-line therapy, corticosteroids for high-risk cases, and targeted therapies, such as targeted-release formulation budesonide, sparsentan, and iptacopan, which have shown strong evidence in clinical trials.Experimental biologics, including B-cell activating factor/a proliferation-inducing ligand-targeted therapies and plasma cell-directed therapies, are under investigation.This review provides an overview of the pathogenesis, diagnostic approaches, and recent advances in the treatment of IgAN, with a focus on novel therapeutic strategies emerging from recent clinical trials and revised KDIGO guidelines.Despite great developments in understanding IgAN, universal therapy remained problematic.Supportive care is still the cornerstone, while novel targeted therapies have enhanced outcomes for patients with persistent proteinuria.Early detection, individualized treatment guided by biopsy findings, and ongoing exploration of complement and B-cell-modulating therapies represent the future of precision management in IgAN.