Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2: 139–274.
Bertsias GK, Tektonidou M, Amoura Z, et al; European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31. PubMed PMID: 22851469; PubMed Central PMCID: PMC3465859.
Definition, Etiology, PathogenesisTop
Membranoproliferative glomerulonephritis (MPGN) 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 classified on the basis of the underlying pathology into either immune complex–mediated MPGN or complement-mediated MPGN. In both cases complement ultimately causes damage to the glomerulus. However, in immune complex–mediated MPGN the initiating event is immune complex deposition, which activates complement, whereas with complement-mediated MPGN there is underlying inappropriate and continuous complement activation due to dysregulation of the complement system.
The majority of immune complex–mediated MPGN is caused by infections, with most of those being caused by hepatitis C with cryoglobulinemia. Less common causes of immune complex–mediated MPGN include monoclonal gammopathies and autoimmune conditions (most commonly lupus). Complement-mediated MPGN is less common than immune complex–mediated MPGN and is usually due to either an acquired (genetic) defect or autoimmune removal (antibodies) of complement or complement regulatory proteins. An older classification system separated MGPN into classes I, II, and III based on the appearance on electron microscopy and this classification can still be found in the literature.
MPGN that is acquired or autoimmune 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.
MPGN that is secondary to another condition is associated with signs and symptoms of the underlying condition. When MPGN is associated with hepatitis C–induced cryoglobulinemia, it is often accompanied by weakness, arthralgias, and purpura, which preferentially affects the lower extremities.
There is no universally accepted treatment regimen for MPGN, as the evidence is of generally low quality. For idiopathic immune complex–mediated MPGN, patients with proteinuria >3.5 g/d and/or a progressive decline of glomerular filtration rate (GFR), immunosuppressive treatment may be attempted, with the appropriate choice of medication being unclear.
Treatment for immune complex–mediated MPGN secondary to an underlying condition should be targeted towards the underlying condition. Evidence for complement-mediated MPGN is less clear given the rarity of the disease. Immunosuppression and complement inhibitors may be attempted in those with significant proteinuria or declining renal function.
Idiopathic MPGN is usually progressive. Approximately 50% of patients reach end-stage renal disease by 10 years. In secondary MPGN effective treatment of the underlying condition usually leads to at least partial remission.