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  • Characterized by granular deposits of immunoglobins (IgG) and complement (C3) on the capillary walls that accumulate, causing the glomerular basement membrane to abnormally thicken
  • Patients typically present with extremely high levels of proteinuria, edema, hypoalbuminemia, and hyperlipidemia1
  • Thickened walls become damaged and leak protein into the urine2
  • 75-80% of patients present with antibodies to M-type phospholipase A-2 receptors (PLA2R) located on podocytes
  • Production of the anti-PLA2R antibodies results in primary (idiopathic) MN1
    • Primary MN is the most common cause (20-40%) of non-diabetic related idiopathic nephrotic syndrome in Caucasian adults2
  • The remaining patients have secondary MN from an autoimmune disease, malignancy, drugs, infection, or non-identified autoantibodies1
  • Incidence rate estimated to be about 12 patients/million in the United States
  • Higher male dominance
    • 2:1 male-to-female ratio
    • Usually diagnosed in men 50-60 years of age
  • Most common in Caucasians, followed by people of Asian, African, or Hispanic ancestry
  • Prognosis among patients widely varies and typically follows a rule of thirds:
    • 1/3 will undergo spontaneous remission (among patients with absent or low anti-PLA2R antibodies)
    • 1/3 will experience end-stage renal disease (ESRD)
    • 1/3 will develop non-progressive chronic kidney disease (CKD)2
  • MN gradually progresses and can be identified into a four-stage classification:
    • Stage 1 — presence of scattered small immune complex-type deposits on the epithelial side without glomerular basement membrane thickening
    • Stage 2 — spiky projections of basement membrane extending between the subepithelial deposits and thickening of the glomerular basement membrane
    • Stage 3 — larger deposits surrounded by basement membrane
    • Stage 4 — irregular thickening and incorporation of deposits in the basement membrane3

Recommendations are based on the KDIGO Clinical
Practice Guideline for Glomerulonephritis

  • Treatment aimed towards remission of proteinuria to preserve kidney function and ensure patient survival
    • Prognosis goals: proteinuria reduction, complete or partial remission of nephrotic syndrome, and stable or improved renal function
  • Options are based on degree and persistence of nephrotic-range proteinuria
  • Initial therapy upon diagnosis should consist of alternating monthly cycles of corticosteroids and oral alkylating agents, also known as the Ponticelli Regimen
    • KDIGO recommends cyclophosphamide over chlorambucil for the alkylating agent
    • At least 6 months of treatment until remission
  • Calcineurin inhibitors (CNIs) are prescribed first line of defense if patients choose not to receive the corticosteroids/alkylating agents therapy or have contraindications
    • Options include cyclosporine and tacrolimus
  • If a patient is resistant to the corticosteroids/alkylating agents therapy, CNI therapy will be used as an alternative and vice versa
  • As of 2012, the KDIGO guidelines list the following therapies as potential treatment options, but they are not recommended:
    • Corticosteroid monotherapy
    • Mycophenolate mofetil (MMF)
    • Monoclonal antibodies (rituximab)
    • Adrenocorticotropic hormone (ACTH)10

Treatment Options
Immunosuppressive Therapy
Corticosteroids10
  • Methylprednisolone
    		• Cytotoxic Agents10
  • Chlorambucil (Leukeran®)
  • Cyclophosphamide (Cytoxan®)
    • Calcineurin Inhibitors10
  • Cyclosporine (Gengraf®)
  • Tacrolimus (Prograf®)
    		• Immunosuppressive Agents10
  • Mycophenolate mofetil (CellCept®)
    • Monoclonal Antibodies10
  • Rituximab (Rituxan®)
    		• Acthar® Gel10*

    *FDA approved, but not enough contemporaneous data for KDIGO to make a use recommendation