The Role of Renal PLA2R Staining Combined with Serum PLA2R Antibody in Membranous Nephropathy Risk Stratification

Background: This study aimed to examine the clinicopathological profiles and prognosis of membranous nephropathy in different subtypes classified by serum PLA2R antibody (SAb) and glomerular PLA2R antigen staining (GAg). Methods: A total of 372 biopsy-proven membranous nephropathy (MN) cases, unrelated to lupus, with urine protein > 2 g/24 h and eGFR > 25 mL/min/1.73 m(2) were included and categorized into four groups according to the presence or absence of PLA2R antibody and glomerular PLA2R antigen staining. Clinical profiles were compared among four subtypes. Treatment response and renal outcomes were compared among four groups with primary MN. Cox and logistic regression models were used to examine the association between time-to-renal progression and early remission within 6 months in the four subgroups with primary MN. Results: MN patients who were SAb-/GAg+ presented with a more severe disease onset, whereas those who were SAb-/GAg- had a mild clinical manifestation with a higher prevalence of MN-associated secondary causes. During a median follow-up of 79.2 months (IQR: 48.70-97.40), SAb+/GAg- was identified as an independent risk factor for renal progression [HR: 9.17, 95% CI: 2.26-37.16, p < 0.01] and early remission [OR: 0.06, 95% CI: 0.01-0.56, p = 0.01] in primary MN. Additionally, SAb-/GAg- with primary MN showed an independent association with spontaneous remission after adjusting for age, sex, baseline proteinuria, and eGFR (Before adjustment: OR: 8.33, 95% CI: 1.89-36.76, p = 0.0; after adjustment: OR: 12.25, 95% CI: 2.48-60.53, p < 0.01). Conclusion: Our findings indicated that SAb+/GAg-MN patients exhibited a more severe disease onset and had a poorer prognosis, necessitating an aggressive treatment approach. On the other hand, in the SAb-/GAg- group, the elimination of secondary causes should be considered, and a watchful waiting approach may be appropriate.