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Definition, Etiology, PathogenesisTop
Membranoproliferative glomerulonephritis (MPGN) (also called mesangiocapillary glomerulonephritis) is characterized by diffuse proliferation of the mesangium and thickening of the capillary walls. It is a rare disease, accounting for <10% of glomerular diseases.
MPGN is traditionally classified based on electron microscopy as type I, II, or III. Type I is distinguished by immune complex and complement deposits in the glomerular subendothelial space and mesangium. Type III is considerably less common and has a similar appearance to type I with additional deposits in the subepithelial space. Secondary causes of types I and III are similar. Type II (also known as dense deposit disease) results from excess activity of the alternative complement pathway leading to deposits in the mesangium and glomerular basement membrane. More recently, a new classification system has been developed that reflects the underlying pathology rather than the histologic appearance and delineates MPGN by either immune complex–mediated disease or complement-mediated disease.
The majority of patients have secondary MPGN. Types I and III MPGN can be caused by chronic infections, with hepatitis C–induced cryoglobulinemia leading to type I MPGN as a common etiology. Other chronic infections such as hepatitis B, endocarditis, and fungal and parasitic infections also lead to MPGN, with the prevalence of each varying depending on the local prevalence of the underlying infection. Connective tissue diseases, particularly systemic lupus erythematosus, Sjögren syndrome, and rheumatoid arthritis, as well as monoclonal gammopathies are additional causes. Type II MPGN/dense deposit disease is less common and can be caused by inherited or acquired defects in complement regulation.
Primary MPGN occurs mainly between the ages of 5 and 30 years. Presentation varies and can include asymptomatic hematuria and proteinuria, nephrotic syndrome, and rarely rapidly progressive glomerulonephritis. Hypertension is common and present in most patients. Levels of C3 are low and C4 may be low.
Secondary MPGN is associated with signs and symptoms of the underlying condition. When MPGN is associated with cryoglobulinemia, it is often accompanied by weakness, arthralgias, and purpura, which preferentially affects the lower extremities.
There is no universally accepted treatment regimen for primary MPGN, as the evidence is weak. In patients with proteinuria >3.5 g/d and a progressive decline of glomerular filtration rate (GFR), immunosuppressive treatment may be attempted, with prednisone combined with either oral cyclophosphamide or mycophenolate mofetil.
In secondary MPGN treatment should be targeted towards the underlying condition. However, immunosuppression with glucocorticoids and cyclophosphamide, plasmapheresis, or rituximab in addition to treatment of hepatitis C is suggested in the setting of hepatitis C–caused cryoglobulinemia leading to nephrotic syndrome or a rapid decline of renal function.
Primary MPGN is usually progressive. Approximately 50% of patients will reach end-stage renal disease by 10 years. In secondary MPGN effective treatment of the underlying condition usually leads to at least partial remission.