Monitoring anti-PLA2R antibody titres to predict the likelihood of spontaneous remission of membranous nephropathy

Abstract

Rationale & Objective In antiPLA2R membranous nephropathy (MN), there is controversy whether spontaneous remission (SR) can be predicted using a single titer, or assessing the dynamic changes anti-PLA2Rab titers. The study objective was to identify the optimal dynamics of anti-PLA2Rab titer to predict SR in MN Patients and Method 127 nephrotic patients with antiPLA2R-MN were prospectively followed-up for 6 months under conservative treatment. Anti-PLA2Rab and proteinuria were assessed at diagnosis and monthly thereafter. The primary end-point (PEP) was the reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive antiPLA2Rab titers were developed to predict the PEP. Results 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titers. An anti-PLA2R titer ≤ 97.5 RU/mL at diagnosis, had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rab and a reduction ≥ 15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an AUC significantly higher than that obtained with relative changes of proteinuria at the same period of time [0.95 (95%CI: 0.91-0.98) vs 0.79 (95%CI: 0.70-0.88) respectively p: 0.0013]. Conclusions combining the baseline antiPLA2Rab titers with their relative changes at 3 months after diagnosis, gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy.

PLA2R-IgG4 antibody as a predictive biomarker of treatment effectiveness and prognostic evaluation in patients with idiopathic membranous nephropathy: a retrospective study

“…Patients with high PLA2R-IgG titer is associated with bad renal function and not easily remission. Jatem-Escalante et al (2021) found the model including baseline anti-PLA2Rabs and a reduction ≥15% at three months for predicting spontaneous remission with a sensitivity of 93% and a specificity of 80%, which was better than changes of proteinuria in the same period of time. Our study indicated the higher the PLA2R-IgG4 titer and the decline ratio of PLA2R-IgG4 as well as the lower the eGFR, the more likely the inefficacy.…”

“…But with the discovery of PLA2R and the knowledge advancement on pathogenic mechanism, the PLA2R antibody is regarded as a potential clinical indicator to assess and predict the remission of PLA2R associated IMN, regardless of spontaneous remission or response to immunosuppressive therapy. Although many studies currently are underway or have been published to determine the cut-off value of the PLA2R antibody to predict the remission, no consensus has been reached ( Dahan et al, 2017 ; Jatem-Escalante et al, 2021 ). A recent study indicated that when setting a threshold value for PLA2R antibody detected by ELISA at baseline to 97.5 RU/mL had a sensitivity of 71% and a specificity of 81% to predict the spontaneous remission at the 12th month ( Jatem-Escalante et al, 2021 ).…”

“…Although many studies currently are underway or have been published to determine the cut-off value of the PLA2R antibody to predict the remission, no consensus has been reached ( Dahan et al, 2017 ; Jatem-Escalante et al, 2021 ). A recent study indicated that when setting a threshold value for PLA2R antibody detected by ELISA at baseline to 97.5 RU/mL had a sensitivity of 71% and a specificity of 81% to predict the spontaneous remission at the 12th month ( Jatem-Escalante et al, 2021 ). GEMRITUX trial discovered that anti-PLA2R depletion achieved at 6th month in patients treated with rituximab or supportive treatment was 50% and 12%, respectively.…”

“…With the serum anti- PLA2R antibody becoming negative, it takes a long time to return the glomerular basement membrane (GBM) architecture to normal. Therefore, the PLA2R antibody level precedes the clinical remission and predicts clinical response in the course of spontaneous or treatment-induced remission ( Dahan et al, 2017 ; Jatem-Escalante et al, 2021 ). According to KDIGO guidelines, longitudinal monitoring of PLA2R antibody levels during treatment can guide therapeutic adjustments ( Medrano et al, 2015 ; Wei et al, 2016 ).…”

Prediction Models of Primary Membranous Nephropathy: A Systematic Review and Meta-Analysis

“…Among these eight studies involving 1237 patients, six studies reported prognostic prediction models on renal function deterioration [ 5 , 6 , 7 , 8 , 9 , 17 ], while the other two reported prediction models on proteinuria remission [ 18 , 19 ]. Five and three of the eight studies were retrospective and prospective, respectively.…”