Is this primary membranous nephropathy in an elderly female patient with diabetes (Diabetes Mellitus), nephrotic syndrome, positive Phospholipase A2 Receptor (PLA2R) antibody, severe proteinuria, and impaired renal function (GFR 27)?

Yes, this is primary membranous nephropathy despite the presence of diabetes.

A positive PLA2R antibody test in a patient with nephrotic syndrome is sufficient to diagnose primary membranous nephropathy, even when diabetes or other comorbidities are present. 1

Diagnostic Certainty with Positive PLA2R Antibody

• The high specificity (94%) of anti-PLA2R antibodies allows high-confidence diagnosis of primary MN without requiring kidney biopsy in most cases 1
• Approximately 70-80% of patients with primary MN test positive for anti-PLA2R antibodies, and your patient falls into this category 2, 1
• The 2023 KDOQI/KDIGO guidelines explicitly state that a positive anti-PLA2R antibody test indicates immunologically active primary MN, which is a renal-limited autoimmune disorder 2, 1

Why Diabetes Does Not Change the Diagnosis

• The presence of diabetes does not exclude primary membranous nephropathy. 2
• The KDIGO guidelines specifically note that "a few patients with anti-PLA2R antibodies may also have features of another disorder" and that these conditions may be coincidental rather than causal 2
• Your patient's positive PLA2R antibody indicates the membranous nephropathy is primary (autoimmune), not secondary to diabetes 2, 1
• Diabetic nephropathy typically presents with different histologic features than membranous nephropathy and would not produce PLA2R antibodies 2

When to Consider Kidney Biopsy Despite Positive PLA2R

While the diagnosis is clear, certain clinical features warrant consideration of confirmatory biopsy:

• Rapidly progressive eGFR decline out of proportion to the disease - Your patient's GFR of 27 represents advanced CKD, which may warrant biopsy to assess chronicity and guide treatment intensity 2, 1
• The degree of chronic interstitial fibrosis and tubular atrophy on biopsy is a major prognostic factor and helps determine whether aggressive immunosuppression is appropriate versus conservative management 2
• Biopsy allows assessment of whether the severe kidney dysfunction is reversible or represents irreversible chronic damage 2

Evaluation for Secondary Causes Still Required

• You must still evaluate for associated conditions regardless of positive PLA2R antibody status 2, 1
• Screen for malignancy (especially in elderly patients), lupus, hepatitis B/C, and nephrotoxic medications (NSAIDs) 2, 1
• The positive PLA2R antibody does not exclude these secondary causes; it confirms the MN is primary, but other conditions may coexist 2, 1

Prognostic Implications of PLA2R Antibody Levels

• If you have quantitative PLA2R antibody titers, high levels predict lower rates of spontaneous remission and longer duration of proteinuria 1, 3
• Serial antibody measurements showing trajectory are more informative than isolated values for guiding treatment decisions 1, 3
• Decreasing antibody titers predict subsequent clinical remission, while increasing levels indicate greater risk of prolonged disease 1, 3

Critical Management Considerations for This Patient

Given the severe proteinuria, advanced CKD (GFR 27), and positive PLA2R antibodies:

• This patient is at high risk for disease progression and likely requires immunosuppressive therapy 1, 4
• Rituximab is recommended as first-line treatment for primary MN with nephrotic syndrome and risk factors for progression 5, 4
• The advanced CKD stage makes assessment of chronicity via biopsy particularly important before committing to aggressive immunosuppression 2
• Optimal supportive care is mandatory: RAS blockade, blood pressure control to <130/80 mmHg, and prophylactic anticoagulation given severe proteinuria 5