Abstract

BACKGROUND: The 2021 KDIGO guidelines recommend following anti-PLA2R antibody levels as a marker of treatment response in membranous nephropathy, however the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown.METHODS: We used a cohort of 85 patients from the MENTOR trial with anti-PLA2R antibodies =14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab. Three landmark times were considered: at baseline, and after 3 and 6 months of treatment. Logistic regression model performance was evaluated using C-statistics and model fit (Akaike Information Criterion (AIC), R2).RESULTS: The model at baseline that best predicted no remission included anti-PLA2R antibodies >323 RU/ml and creatinine clearance; the best model after 3 months included the change from baseline in both antibody and albumin levels; and the best model after 6 months included antibody levels >14 RU/ml, creatinine clearance, and the change from baseline in albumin. Compared to the model at baseline, the model at 3 months had better model fit (AIC 70.9 vs 96.4, R2 51.8% vs 30.1%) and higher C-statistic (0.93 vs 0.83, p=0.008). The model at 6 months had no difference in performance compared to the model at 3 months (AIC 68.6, R2 53.0%, C-statistic 0.94 p=0.67).CONCLUSIONS: Using the MENTOR clinical trial cohort of patients with membranous nephropathy treated with standardized cyclosporine or rituximab, we found that the optimal method to evaluate risk factors for the probability of treatment response was to use anti-PLA2R antibody levels combined with albumin levels after 3 months of treatment, which was significantly better than using antibody levels alone or risk factor evaluation at baseline, with no added benefit of waiting until 6 months of treatment.

View details for DOI 10.2215/CJN.0000000000000237

View details for PubMedID 37471101