What is membranoproliferative glomerulonephritis (MPGN)?

From the Guidelines

Membranoproliferative glomerulonephritis (MPGN) patients with severe forms of the disease, such as those with crescents, focal necrosis, and/or rapidly progressive glomerulonephritis (RPGN), should be treated with a regimen similar to that used to treat ANCA-associated vasculitis, including cyclophosphamide or rituximab along with pulse dose intravenous methylprednisolone followed by oral prednisone, as this approach has been recommended in the most recent guideline commentary 1.

Key Considerations

• The treatment of MPGN depends on the underlying cause and the severity of the disease, with immunosuppressive medications and supportive care playing important roles in management.
• Patients with normal eGFR and non-nephrotic range proteinuria may be treated conservatively, while those with advanced chronic kidney disease or severe tubulointerstitial fibrosis should not be treated with immunosuppression 1.
• A trial of steroids in children with MPGN and nephrotic syndrome and/or impaired renal function may be warranted as first-line treatment, with a reasonable approach being a trial of alternate-day steroids for a period of 6 to 12 months 1.

Treatment Approaches

• Immunosuppressive medications, such as corticosteroids, calcineurin inhibitors, or mycophenolate mofetil, may be used to treat MPGN, with the specific choice of medication depending on the underlying cause and severity of the disease.
• Supportive care, including blood pressure control with ACE inhibitors or ARBs and lipid-lowering agents if hyperlipidemia is present, is also important in managing MPGN.
• For complement-mediated MPGN, eculizumab may be considered as a treatment option.

Prognosis

• The prognosis for MPGN varies, with some patients progressing to end-stage kidney disease despite treatment, while others maintain stable kidney function for years with appropriate management.
• Significant poor prognostic variables, such as age, male gender, creatinine and proteinuria at the time of renal biopsy, number of clinical relapses, and poor blood pressure control, should be taken into account when managing MPGN 1.

From the Research

Definition and Classification of Membranoproliferative Glomerulonephritis

• Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury that may be primary or secondary to infections, autoimmune diseases, and hematological disorders 2.
• MPGN has been classified into complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated MPGN (IC-MPGN) based on immunofluorescence findings 2.
• However, this classification leaves a number of issues unresolved, and the finding of genetic and acquired complement abnormalities in both C3G and IC-MPGN indicates that they represent a heterogeneous spectrum rather than distinct diseases 2.

Treatment and Outcome of Membranoproliferative Glomerulonephritis

• An intensive immunosuppressive (IS) regimen combining steroids and alkylating agents in high doses and for a prolonged time is effective in inducing remission and halting progression to end-stage renal disease (ESRD) in patients with MPGN 3.
• The treatment of MPGN is considered by most authors as unrewarding, and the disease progresses to ESRD, but the use of corticosteroids and immunosuppressants may be effective in some cases 3, 4.
• Eculizumab, an anti-C5 monoclonal antibody, has been used occasionally in single cases or small series, but only a few patients have achieved remission, and the response may be related to the extent of terminal complement activation 2.
• Steroids and mycophenolate mofetil seem to be effective in treating MPGN, and for some patients, eculizumab might be a treatment option 5.

Prognosis and Recurrence of Membranoproliferative Glomerulonephritis

• MPGN often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II 4.
• The outcome of MPGN is heterogeneous, and precise differentiation between IC-MPGN and C3G is still pending 5.
• One patient progressed to end-stage renal disease (ESRD) 6 years after disease onset, highlighting the importance of long-term follow-up and monitoring 5.