Anti-PLA2R Antibody Levels and Clinical Risk Factors for Treatment Nonresponse in Membranous Nephropathy

MENTOR Trial investigators, Sean J Barbour, Fernando C Fervenza, Dilshani Induruwage, Paul E Brenchley, Brad Rovin, Michelle Hladunewich, Heather N Reich, Richard Lafayette, Nabeel Aslam, Gerald B Appel, Ladan Zand, Krzysztof Kiryluk, Lili Liu, Daniel C Cattran

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BACKGROUND: The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (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 Membranous Nephropathy Trial Of Rituximab (MENTOR) 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], R 2 ). 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 with the model at baseline, the model at 3 months had better model fit (AIC 70.9 versus 96.4, R 2 51.8% versus 30.1%) and higher C-statistic (0.93 versus 0.83, P = 0.008). The model at 6 months had no difference in performance compared with the model at 3 months (AIC 68.6, R 2 53.0%, C-statistic 0.94, P = 0.67). CONCLUSIONS: In patients with membranous nephropathy treated with cyclosporine or rituximab in the MENTOR trial, 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. PODCAST: This article contains a podcast at

Original languageEnglish
Pages (from-to)1283-1293
Number of pages11
JournalClinical journal of the American Society of Nephrology : CJASN
Issue number10
Early online date20 Jul 2023
Publication statusPublished - 1 Oct 2023


  • Albumins
  • Autoantibodies
  • Creatinine
  • Cyclosporine/therapeutic use
  • Glomerulonephritis, Membranous/drug therapy
  • Humans
  • Receptors, Phospholipase A2
  • Risk Factors
  • Rituximab/therapeutic use


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