ESSENTIALS OF DIAGNOSIS
Nephrotic syndrome is the typical presenting feature.
The glomerular basement membranes (GBMs) appear thickened on light microscopy.
There is an absence of glomerular inflammation.
Primary (PLA2R or THSD7A antigen related) membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults.
Secondary MN forms can account for up to one-third of cases.
Malignancy as a secondary cause increases with age.
Conservative management should be the first step in management.
Risk of progression of the disease needs to be considered because patients with a high risk of progression can benefit from immunosuppressive treatment.
Seventy years ago, E.T. Bell coined the term membranous glomerulonephritis to describe the renal pathology in a group of patients with the clinical features of nephrotic syndrome in whom the kidney biopsy revealed marked glomerular basement membrane (GBM) thickening without significant inflammation. The terms extramembranous nephropathy and epimembranous glomerulonephritis were also used to describe the disease. The word glomerulonephritis is, however, misleading as one of the main features of the condition is the absence of glomerular inflammation; because of this the word nephropathy is now more often used. Idiopathic membranous nephropathy (MN) is a relatively common immune mediated glomerular disease and remains a leading cause of nephrotic syndrome in adults.
Until recently, the primary antigens were was unknown and the disorder was termed idiopathic, but now given the newly recognized two autoantibody systems (PLA2R and THSD7A) it more accurately should be designated primary MN. Secondary forms of MN may account for up to one-third of cases and are associated with autoimmune diseases (eg, systemic lupus erythematosus, SLE), infections (eg, hepatitis B and C viral infections), medications (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], D-penicillamine, gold), and neoplasia (eg, colon kidney, prostate, and breast cancer) (Table 27–1). The presence of phospholipase A2 receptor (PLA2) antibodies or thrombospondin type 1 domain–containing 7A (THSD7A) antibodies (in the serum) or antigen localization on glomerular tissue staining helps in lowering the likelihood of secondary MN. However, since both primary and secondary forms have similar clinical presentations, the designation of primary requires appropriate ruling out of the secondary causes by a careful history, physical examination, and laboratory evaluation of the patient. This disease is rare in children, and when it occurs, is commonly associated with an immunologically mediated disorder such as SLE.
Table 27–1.Secondary membranous nephropathy. ||Download (.pdf) Table 27–1. Secondary membranous nephropathy.
|Infections: Hepatitis B and C, syphilis (congenital and secondary), leprosy, filariasis, hydatid cyst disease, hepatosplenic schistosomiasis, echinococcus, post-streptococcal infection, malaria |
|Neoplasia: Carcinomas, leukemia, lymphoma, pheochromocytoma, carotid body tumor |
|Autoimmune: SLE,1 thyroiditis, rheumatoid arthritis, mixed connective tissue disease, sarcoidosis, angiolymphoid hyperplasia with eosinophilia (Kimura disease), primary biliary cirrhosis, Sjögren syndrome, ankylosing spondylitis, dermatitis herpetiformis |
|Drugs: NSAIDs (diclofenac), gold, D-penicillamine, mercury, captopril, formaldehyde, thiola, probenecid, bucillamine, tiopronin |
|Other: de novo renal transplant, sickle-cell disease, ...|