Membranous glomerulonephritis
Membranous glomerulonephritis is the most common cause of idiopathic nephrotic disease in white patients. It is also secondarily associated with syphilis, HBV and HCV, SLE, some drugs, and tumours.
Primary membranous glomerulonephritis is an autoimmune disease, where antibody-antigen complexes form and are deposited as subepithelial deposits, between the glomerular basement membrane and the podocytes (the epithelial cells). These complexes can form as a result of autoantibodies that directly target elements of the podocytes, such as autoantibodies targeting the M-type phospholipase A2 receptor and Neutral endopeptidase. Alternatively, the complexes can travel from elsewhere in the body, and be deposited subepithelial, for example cationic bovine serum albumin.
These subepithelial deposits then activate the complement system, attacking podocytes and mesangial cells, causing podocyte damage and causing proteins and lipids to escape in the urine.
Clinical presentation of membranous nephropathy is proteinuria and edema, and the not infrequent hypertension and microhematuria, although GFR is usually preserved at presentation. This form of glomerulonephritis is however most commonly associated with a hypercoagulability state and renal vein thrombosis. Sudden flank pain or sudden deterioration of renal function would indicate this.
Diagnosis is based on light microscopy of biopsy. Glomerular capillary loops appear rigid or thickened, and immunofluorescence staining shows subepithelial immune dense deposits all along the capillary loops. Antibodies to the M-type phospholipase A2 receptor are highly specific and sensitive.
Kidney biopsy (silver/PAS stain) in membranous nephropathy: glomerular capillary loops with diffusely thickened, rigid basement membranes and no increase in cells.
Image: “Membranous nephropathy - cropped - mpas - very high mag” by Nephron, CC BY-SA 3.0, via Wikimedia Commons.
Treatment should be combination corticosteroid therapy
- Month 1, 3 and 5
- 1g IV methylprednisolone for 3 days then prednisolone 0.5mg/kg/day orally for 27 day
- Month 2, 4 and 6
- Oral cytotoxic therapy of cyclophosphamide 2mg/kg/day + prednisone 0.15mg/kg/day
Prognosis is average, 75% survival at 10 years with spontaneous remission of 30%