(1) Background: We sought to investigate the clinical outcome and to identify the independent predictors of clinical remission in a prospectively followed cohort of patients with primary membranous nephropathy (pMN). (2) Methods: We conducted a prospective, observational, non-interventional study that included 65 consecutive patients diagnosed with pMN between January 2015 and December 2019 at our department and followed for at least 24 months. The primary outcomes evaluated during the follow-up period were the occurrence of immunological and clinical remission (either complete or partial remission). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent predictors of clinical remission. (3) Results: In the study cohort, 13 patients had a PLA2R-negative pMN, while, of those with PLA2R-associated pMN, 27 patients had a low anti-PLA2R antibody titer (<200 RU/mL), and 25 patients had a high anti-PLA2R antibody titer at baseline (≥200 RU/mL). The clinical outcome was better in patients with PLA2R-negative pMN compared to patients with PLA2R-positive pMN. These patients had a higher percentage of complete remissions (46.2%, compared to 33.3% in those with low anti-PLA2R antibody titer or 24% in those with high anti-PLA2R antibody titer), a faster decline of 24 h proteinuria and lower time to complete remission. In multivariate Cox regression analysis, patients with PLA2R-negative pMN had a 3.1-fold and a 2.87-fold higher chance for achieving a complete or partial remission compared to patients with high anti-PLA2R antibody titer or to all PLA2R-positive patients, respectively. Additionally, patients with a baseline 24 h proteinuria of less than 8 g/day and with an immunological remission at 24 months had a 2.4-fold (HR, 2.4; 95%CI, 1.19-4.8) and a 2.2-fold (HR, 2.26; 95%CI, 1.05-4.87), respectively, higher chance of achieving a clinical response. By contrary, renal function at diagnosis, type of therapeutic intervention or anti-PLA2R antibody titer did not predict the occurrence of clinical remission. (4) Conclusions: We identified a different clinical phenotype between PLA2R-positive and PLA2R-negative pMN. Additionally, we have shown that baseline proteinuria seems to be a more important predictor of clinical outcome than anti-PLA2R-ab titer.
Keywords: anti-PLA2R antibodies; clinical remission; immunosuppressive treatment; primary membranous nephropathy; proteinuria; spontaneous remission.