membranoproliferatieve

Membranoproliferative (MPGN) is a group of kidney disorders characterised by inflammatory changes of the glomerular basement membrane and subendothelial space, leading to secondary deposition of immune complexes or complement activation. The condition is classified into three main types according to electron microscopy and immunofluorescence findings: type I, type II (dense deposition disease), and type III, which contains elements of both type I and III. In addition, evolving research has introduced a subclassification based on complement dysregulation, resulting in categories such as C3 glomerulopathy.

The aetiology of MPGN is heterogenous. In type I, infection‑associated immune complexes, autoimmune diseases such as systemic lupus erythematosus, or paraproteinemia can trigger the disease. Type II is predominantly driven by complement alternative pathway dysregulation, often associated with mutations in complement regulatory proteins or autoantibodies such as factor H anti‑factor H. In type III, a combination of mechanisms involving both immune complex deposition and complement activation are present. Prognosis varies with type; type I shows a more favourable outcome when adequately treated, whereas type II and certain complement‑mediated forms carry a higher risk of progression to end‑stage renal disease.

Clinical presentation often includes nephrotic syndrome, hematuria, and reduced glomerular filtration rate. Diagnosis is based on a renal biopsy showing characteristic double contours of the glomerular basement membrane, mesangial expansion, and fibrinoid necrosis on light microscopy, with subendothelial deposits on electron microscopy. Immunofluorescence patterns differ: IgG and C3 dominance in type I, C3 alone in type II, and mixed patterns in type III. Treatment aims to control proteinuria and hypertension with renin‑angiotensin system blockers, and to target underlying pathophysiology. Immunosuppressive agents such as corticosteroids, cyclophosphamide or mycophenolate mofetil are used in immune‑complex mediated forms; in complement‑mediated disease, complement inhibition with eculizumab or novel factor H‑targeted therapies is under investigation. Early recognition and targeted therapy improve long‑term renal survival.