What is the trend of Phospholipase A2 (PLA2) receptor antibodies in Membranous Nephropathy?

From the Guidelines

PLA2 receptor antibody levels should be monitored regularly in patients with membranous nephropathy, as they correlate with disease activity and treatment response. Specifically:

• Test PLA2R antibodies at diagnosis and every 3-6 months during treatment, as changes in anti-PLA2R antibody levels precede and predict changes in clinical parameters, such as proteinuria 1
• A decrease in antibody levels often precedes clinical remission, and disappearance of anti-PLA2R antibodies should lead to refraining from additional therapy 1
• Rising levels may indicate impending relapse, and the likelihood of spontaneous remission is inversely related to the degree of detectable antibody at the time of diagnosis 1
• Target complete disappearance of antibodies for optimal outcomes, as this is associated with improved long-term prognosis 1 Monitoring protocol:

1. Baseline test at diagnosis
2. Repeat every 3 months during initial treatment
3. If remission achieved, test every 6 months
4. With any clinical change (e.g. increasing proteinuria), test immediately PLA2R antibodies are pathogenic in membranous nephropathy, binding to podocyte antigens and causing proteinuria, and their levels reflect ongoing autoimmune activity 1. Tracking antibodies allows for earlier detection of treatment response or disease recurrence compared to clinical markers like proteinuria alone, enabling more timely adjustments to immunosuppressive therapy, potentially improving long-term outcomes 1. The most recent and highest quality study, 1, supports the use of anti-PLA2R antibody levels to guide treatment decisions, and this approach is also recommended in the 2021 KDIGO guideline for the management of glomerular diseases 1.

From the Research

Trend of Phospholipase A2 (PLA2) Receptor Antibodies in Membranous Nephropathy

• The level of PLA2R antibodies is associated with disease activity and clinical outcome in patients with primary membranous nephropathy 2.
• A decrease in PLA2R antibody level is associated with a decrease in proteinuria in patients with primary MN 2.
• Patients with high PLA2R antibody levels achieve remission of proteinuria significantly later than patients with low PLA2R antibody levels 2.
• PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria 2.

Association with Treatment Response

• The optimal method to evaluate risk factors for the probability of treatment response is to use anti-PLA2R antibody levels combined with albumin levels after 3 months of treatment 3.
• PLA2R antibody level is an independent predictive factor for complete remission and total remission 4.
• Patients with high PLA2R antibody levels (>150 RU/ml) have lower complete remission and total remission rates compared to those with non-high titer antibody 4.

Treatment Outcomes

• Rituximab seems effective and reasonably safe in PLA2R-associated membranous nephropathy with stage 4 or 5 chronic kidney disease 5.
• RTX therapy might be an effective and safe treatment in patients with PLA2R-associated MN and malignancy 6.
• Cyclophosphamide combined with corticosteroids is preferred compared to tacrolimus plus corticosteroids in patients with high PLA2R antibody levels, although serious adverse events are more frequent in the former 4.