MEMBRANOUS NEPHROPATHY: PATHOGENIC MECHANISMS, DIAGNOSIS, AND THERAPEUTIC APPROACHES

Abstract

Membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults and is characterized by thickening of the glomerular basement membrane due to the deposition of immune complexes, being an immune-mediated disease that can occur in either a primary or secondary form. Primary MN is often associated with the presence of autoantibodies directed against the phospholipase A2 receptor (PLA2R), which has been a crucial discovery in understanding its pathophysiology. The secondary form, on the other hand, may be related to conditions such as chronic infections (hepatitis B and C), neoplasms, the use of certain medications, and autoimmune diseases, such as systemic lupus erythematosus. The diagnosis of MN is primarily based on renal biopsy, which reveals thickening of the glomerular capillary loops and subepithelial deposits, confirmed by electron microscopy and immunofluorescence. Clinically, MN manifests with nephrotic proteinuria, hypoalbuminemia, and edema, with proteinuria being one of the most significant markers for prognosis. The management of the disease involves the use of immunosuppressants, especially in primary cases, with rituximab, cyclophosphamide, and calcineurin inhibitors playing important roles. However, the response to treatment is variable, with some patients experiencing spontaneous remissions, while others progress to chronic renal failure. In secondary cases, the treatment focuses on the underlying condition. Despite advances, MN remains a therapeutic challenge, with prognosis influenced by various factors, including the response to therapy and the severity of proteinuria. New approaches, such as the use of biomarkers to monitor disease activity, have shown promise in the management of membranous nephropathy.