From the Guidelines
Primary membranous nephropathy (MN) patients, especially those over 50 years old, should undergo age-appropriate cancer screening at diagnosis and periodically for at least 2 years after MN diagnosis, as there is a greater-than-expected frequency of cancer in these patients. When a patient is diagnosed with MN, it is essential to consider the possibility of an underlying malignancy, as the clinical presentation may be difficult to distinguish from that of idiopathic MN 1. The occurrence of malignancy in patients with MN may be causative in some cases and coincidental in others.
Key Considerations
- Age-appropriate cancer screening, such as colonoscopy, mammography, prostate-specific antigen testing, and chest imaging, should be performed at diagnosis and repeated periodically for at least 2 years after MN diagnosis.
- Additional targeted testing may be warranted based on risk factors or symptoms.
- The connection between MN and cancer involves tumor antigens triggering an immune response that cross-reacts with podocyte antigens in the kidney.
- Unlike idiopathic MN, which is often associated with anti-PLA2R antibodies, cancer-associated MN frequently lacks these antibodies.
Treatment Approach
- Treatment should focus on addressing the underlying malignancy, as successful cancer treatment often leads to remission of the nephropathy.
- Immunosuppressive therapy for MN should generally be avoided until cancer has been ruled out or treated, as it may worsen the malignancy, as suggested by the 2012 KDIGO clinical practice guideline for glomerulonephritis commentary 1.
- It is impractical to rule out all secondary causes, but limiting a malignancy workup in patients with MN to age-appropriate cancer screening unless specific risk factors or symptoms suggest the need for additional testing is a reasonable approach 1.
From the Research
Primary Membranous Nephropathy and Cancer
There is no direct evidence in the provided studies to suggest a link between primary membranous nephropathy (pMN) and cancer.
Treatment of Primary Membranous Nephropathy
- The treatment of pMN has evolved to include immunosuppressive drugs such as rituximab, which is now considered a first-line therapy for patients with pMN 2, 3, 4, 5, 6.
- Rituximab has been shown to be effective in achieving remission in 60-80% of patients with pMN 2.
- The use of rituximab in combination with other immunosuppressive agents, such as cyclophosphamide and prednisone, has also been shown to be effective in achieving complete remission in patients with pMN 5.
- The treatment of patients with rituximab-refractory pMN remains controversial and challenging, with several mechanisms proposed to explain rituximab resistance, including decreased rituximab bioavailability, immunization against rituximab, and chronic glomerular damage 2.
Efficacy and Safety of Rituximab
- Rituximab has been shown to be safe and effective in achieving remission in patients with pMN, with a low rate of serious adverse events 4, 5, 6.
- The efficacy of rituximab in achieving complete remission has been reported to be higher when used in combination with other immunosuppressive agents, such as cyclophosphamide and prednisone 5.
- The safety profile of rituximab has been reported to be superior to that of other immunosuppressive agents, such as steroids and calcineurin inhibitors 6.