From the Guidelines
The next best step in evaluating a patient with membranous nephropathy and significant proteinuria, especially with a smoking history, is to screen for underlying malignancy, and the most appropriate test to perform next would be a noncontrast CT of the chest, given the patient's history of smoking. This approach is based on the recommendations from the Kidney International study 1, which suggests that patients with membranous nephropathy, particularly those older than 60 years, should be considered for cancer screening following age-appropriate guidelines. Given the patient's significant smoking history, a noncontrast CT of the chest is a crucial initial step in evaluating for potential malignancies, especially lung cancer. Other evaluations, such as serologic testing for anti-phospholipase A2 receptor (anti-PLA2R) antibodies, testing for hepatitis B, hepatitis C, HIV, and autoimmune conditions like lupus, and proteinuria management with ACE inhibitors or ARBs, are also important but secondary to the initial screening for malignancy. The Canadian Society of Nephrology commentary 1 and the cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome workshop recommendations 1 provide additional context on the management of membranous nephropathy, but the most recent and highest quality study 1 prioritizes cancer screening in this patient population. Key points to consider in the management of this patient include:
- Screening for underlying malignancy with age-appropriate cancer screenings
- Serologic testing for anti-phospholipase A2 receptor (anti-PLA2R) antibodies to distinguish between primary and secondary membranous nephropathy
- Testing for hepatitis B, hepatitis C, HIV, and autoimmune conditions like lupus
- Proteinuria management with ACE inhibitors or ARBs
- Consideration of immunosuppressive therapy if proteinuria persists.
From the Research
Evaluation of Membranous Nephropathy
The patient presents with a 4-week history of lower extremity edema, significant proteinuria (6300 mg/24 h), and a diagnosis of membranous nephropathy with negative staining for the phospholipase A2 receptor antigen. Given the patient's history of smoking and the presence of membranous nephropathy, there is an increased risk of malignancy-associated membranous nephropathy 2, 3, 4.
Risk Factors for Malignancy-Associated Membranous Nephropathy
- Age: The patient is 69 years old, which increases the risk of malignancy-associated membranous nephropathy 2, 3, 4.
- Smoking history: The patient has a 45-pack-year history of smoking, which is a risk factor for malignancy-associated membranous nephropathy 2.
- Negative phospholipase A2 receptor staining: This suggests a higher likelihood of malignancy-associated membranous nephropathy 3.
Next Steps in Evaluation
Given the high risk of malignancy-associated membranous nephropathy, the next step in evaluation should be to investigate for potential malignancies.
- A non-contrast CT of the chest would be a reasonable initial test to evaluate for lung cancer, which is one of the most common types of cancer associated with membranous nephropathy 2, 3, 4.
- Other tests, such as a colonoscopy, have already been performed and were normal.
- The other options, such as kidney and renal vein Doppler ultrasonography, lower extremity Doppler ultrasonography, and random (spot) urine protein-creatinine ratio, are not directly relevant to evaluating for malignancy-associated membranous nephropathy.
Recommended Test
The most appropriate test to perform next would be a non-contrast CT of the chest (Option C) to evaluate for potential malignancies, particularly lung cancer 5.