Approximately 75% of MN cases in adults are primary / idiopathic and renal limited. The remaining cases are secondary to underlying conditions such as infections, malignancies, and systemic autoimmune diseases, as well as certain medications. Secondary MN is more common in children than adults.
MN is characterized by biopsy findings on light microscopy consisting of uniform thickening of the glomerular basement membrane (GBM) without cellular proliferation or infiltration; immunofluorescence reveals immunoglobulin G (IgG; mainly IgG4) and complement fraction C3 staining along the GBM. Most cases of primary MN are mediated by IgG4 antibodies to podocyte membrane antigens M-type phospholipase A2 receptor (anti-PLA2R; 70%-80% of cases) or thrombospondin type 1 domain containing 7A (anti-THSD7A; 2%-7% of cases). Over time, immune complex deposition or formation in situ resulting in complement activation accumulates to high enough levels to cause podocyte injury, leading to nephrotic syndrome (> 3.5 g/day of proteinuria). Such autoantibodies appear absent or very uncommon in patients with secondary MN, although further studies are needed to validate this distinction.
Patients with MN typically present with subacute development of lower extremity edema due to the gradual development of nephrotic-range proteinuria. A majority (70%) are not hypertensive at presentation and have normal renal function. Prognosis is generally good, with either spontaneous or treatment-related remission of MN and a slow progression of renal dysfunction. Approximately 10%-20% of patients with MN progress to end-stage renal disease (ESRD). Risk factors for progression to ESRD include nephrotic-range proteinuria (particularly > 8-10 g/day), increased age (particularly > 50 years), male sex, decreased glomerular filtration rate (GFR) and increased serum creatinine, and persistent elevated anti-PLA2R levels after therapy.
N03.2 – Chronic nephritic syndrome with diffuse membranous glomerulonephritis
77182004 – Membranous glomerulonephritis
- Minimal change disease
- Renal amyloidosis (primary, secondary)
- Lupus nephritis (see glomerulonephritis)
- Diabetic nephropathy
- Focal segmental glomerulosclerosis
- Membranoproliferative glomerulonephritis
- IgA nephropathy
- Immunoglobulin A vasculitis (formerly Henoch-Schönlein purpura nephritis)
- Anti-GBM disease
- ANCA-associated vasculitides
- Light-chain deposition disease
- Infections – hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), parasites (eg, schistosomiasis, malaria)
- Malignancies – solid tumors (eg, lung, prostate), hematologic disorders (eg, plasma cell dyscrasias, non-Hodgkin lymphoma, chronic lymphocytic leukemia)
- Autoimmune diseases – systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, dermatomyositis, ankylosing spondylitis, sarcoidosis
- Alloimmune diseases – de novo MN in transplants / transplant glomerulopathy, graft-versus-host disease
- Drugs / toxins – NSAIDs and COX-2 inhibitors, gold, penicillamine, captopril, mercury, lithium, environmental air pollution