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Anti-phospholipase A2 receptor positive membranous nephropathy: investigating the link between electron microscopy
Gabriel Stefan1,2, George Terinte Balcan1,3, Nicoleta Petre1,2
1Nephrology Department, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.
Abstract:
This retrospective, observational study sought to examine the relationship between Ehrenreich-Churg electron microscopy (EM) stages and long-term outcomes in anti-PLA2R membranous nephropathy (MN). Seventy-one patients with anti-PLA2R MN (median titer 185.7RU/mL) were followed for a median of 46 months, with end-stage kidney disease (ESKD) as the primary endpoint, and response to treatment as a secondary endpoint. Patients were grouped into stages I-II (41 patients) and stages III-IV (30 patients) for analytical purposes. Notably, the III-IV group demonstrated a lower eGFR, lower anti-PLA2R titer, but a higher chronicity score. Kaplan-Meier analysis showed shorter mean kidney survival time in stages III-IV compared to I-II (p 0.03). However, multivariate analysis using Cox regression indicated that Ehrenreich-Churg stages did not significantly influence kidney survival, but lower eGFR at diagnosis and higher histopathological chronicity score did. Remission was achieved by 64% of patients and no relationship between Ehrenreich-Churg stages and treatment response was found. The only identified risk factor for not achieving remission was the severity of hyposerinemia at diagnosis. In conclusion, while EM stages III-IV are associated with more chronic lesions and stages I-II with more active immunologic disease, the histological chronicity score seems to be a stronger predictor of long-term outcomes.
Insights
Electron microscopy stages in anti-PLA2R membranous nephropathy (MN) did not predict kidney survival. Histological chronicity score and lower eGFR at diagnosis were stronger predictors of long-term outcomes in MN patients.
Area of Science:
- Nephrology
- Pathology
- Immunology
Background:
- Anti-phospholipase A2 receptor (anti-PLA2R) membranous nephropathy (MN) is a leading cause of adult primary glomerulonephritis.
- Electron microscopy (EM) staging by Ehrenreich-Churg classifies MN based on subepithelial immune deposits.
- The prognostic value of EM stages in long-term anti-PLA2R MN outcomes requires further clarification.
Purpose of the Study:
- To investigate the association between Ehrenreich-Churg EM stages and long-term clinical outcomes in patients with anti-PLA2R MN.
- To identify predictors of kidney survival and treatment response in this cohort.
Main Methods:
- Retrospective, observational study of 71 patients with anti-PLA2R MN.
- Patients categorized into Ehrenreich-Churg EM stages I-II (n=41) and III-IV (n=30).
- Analysis included Kaplan-Meier survival, Cox regression, and assessment of remission rates.
Main Results:
- Stages III-IV showed lower eGFR and anti-PLA2R titers but higher chronicity scores compared to stages I-II.
- Kaplan-Meier analysis indicated shorter kidney survival in stages III-IV (p=0.03).
- Multivariate analysis revealed eGFR and chronicity score, not EM stage, as significant predictors of kidney survival. Remission (64%) was associated with hyponatremia severity, not EM stage.
Conclusions:
- Ehrenreich-Churg EM stages I-II correlate with more active immunologic disease, while stages III-IV suggest more chronic kidney lesions.
- Histological chronicity score and baseline eGFR are more robust predictors of long-term kidney outcomes in anti-PLA2R MN than EM stages.
- Hyponatremia severity is a key factor influencing treatment response in anti-PLA2R MN.
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