Association of anti-PLA₂R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy

Abstract

Background: The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate.

Design, setting, participants, & measurements: This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA.

Results: In total, 48 patients (37 men) were included. The median age was 55 years (range, 34-75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98-3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab-positive patients, treatment resulted in a rapid decrease of antibodies: median anti-PLA2R-ab, 428 U/ml (range, 41-16,260 U/ml) at baseline and 24 U/ml (range, 0-505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003).

Conclusions: These data suggest that in PLA2R-ab-positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course.

Keywords: anti-PLA2R antibodies; disease course; immunosuppressive; membranous nephropathy; therapy.

Figure 1.

Flow chart of phospholipase A₂ receptor (PLA₂R) antibody–positive patients with idiopathic membranous nephropathy and outcome through up to 5 years of follow-up.

Figure 2.

Kaplan–Meier plot for survival in remission, grouped by PLA₂R antibody status at end of therapy. Numbers of patients at each time point are given below the figure. Log-rank test chi-square=37.05; P<0.001.

Figure 3.

Clinical and immunological remission in time. Percentage remissions in patients in whom PLA₂R antibody had disappeared.