Membranous Nephropathy – Interesting Facts

Membranous Nephropathy

Membranous Nephropathy is a common immune-mediated glomerular disease that remains the leading cause of nephrotic syndrome in white adults.

It is a histologic diagnosis based on the presence of immunoglobulins (Ig; usually IgG and C3) deposition along the capillary walls on immunofluorescence microscopy and subepithelial deposits along the glomerular basement membrane (GBM) on electron microscopy (EM).

Membranous Nephropathy can be either a primary or secondary disease.

Secondary Membranous Nephropathy is caused by:

• • Autoimmune diseases
  • • Systemic lupus erythematosus
  • • Autoimmune thyroiditis
  • • Rheumatoid arthritis
  • • Sjögren syndrome
• • Infections
  • • Hepatitis B
  • • Hepatitis C
  • • Malaria
  • • Schistosomiasis
  • • Tuberculosis
  • • Leprosy
• • Drugs
  • • Penicillamine
  • • Gold
  • • Nonsteroidal antiinflammatory drugs
  • • Captopril
• • Malignancies
  • • Prostate cancer
  • • Lung cancer
  • • Colon cancer
  • • Stomach cancer
  • • Breast cancer
  • • Cervical cancer
  • • Lymphoma
  • • Leukemia

10 Interesting Facts of Membranous nephropathy

1. Membranous nephropathy (MN) remains the leading cause of nephrotic syndrome in white adults. Patients who remain nephrotic are likely to progress to ESKD and are also at an increased risk for thromboembolic and cardiovascular events.

2. Antibodies against podocyte proteins such as M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain containing 7A are responsible for approximately 80% of cases of primary MN.

3. Secondary causes of MN include autoimmune diseases, infection, and malignancies.

4. Up to 70% of patients with MN will have nephrotic syndrome at the time of presentation. MN is a chronic disease, with spontaneous remission and relapses clearly documented.

5. The standard model for the identification of patients at risk for progression to ESKD was developed by the Toronto Glomerulonephritis Registry. This model considers the initial creatinine clearance (CrCl), the slope of the CrCl, and the lowest level of proteinuria during a 6-month observation period, but new models incorporating PLA2R titers are being developed.

6. Conservative therapy consists of restricting dietary protein intake and controlling blood pressure, hyperlipidemia, and edema. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are effective antihypertensive medication. However, their antiproteinuric effect is poor (average proteinuria reduction approximately 30%), and they work best in patients with lower degrees of proteinuria.

7. The use of immunosuppression in the setting of primary MN should be reserved for those patients with deteriorating kidney function and/or heavy proteinuria that persist despite conservative therapy, and/or have high anti-PLA2R antibody levels.

8. Current data suggest that new therapeutic agents such as rituximab and synthetic adrenocorticotropic hormone are effective in reducing proteinuria while having few adverse effects.

9. Membranous nephropathy can recur after kidney transplantation in close to 50% of patients and can result in proteinuria, allograft dysfunction, and graft loss. Recurrence most often occurs during the first year.

10. The relationship between anti-PLA2R antibody levels in patients with MN and clinical response to different treatment modalities needs to be evaluated further.