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Abstract: TH-PO998

Anti-PLA2R Antibodies and Outcome in Patients with Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • van de Logt, Anne-Els, Radboud University Medical Center, Nijmegen, Netherlands
  • Justino, Joana, Institut de Pharmacologie Moleculaire et Celluleire, Sophia Abtipolis, France
  • Vink- van Setten, Coralien, Radboud University Medical Center, Nijmegen, Netherlands
  • van den Brand, Jan A.J.G., Radboud University Medical Center, Nijmegen, Netherlands
  • Lambeau, Gerard J., Institute of Molecular and Cellular Pharmacology, CNRS and University of Nice, Valbonne, France
  • Wetzels, Jack F., Radboud University Medical Center, Nijmegen, Netherlands
Background

Personalized treatment for patients with membranous nephropathy (MN) requires accurate prediction of disease course at an early stage. We evaluated the added value of including level of anti-PLA2R antibodies (PLA2Rab) and epitope spreading at baseline in prediction models.

Methods

We included untreated patients with PLA2R-related MN who were referred to our clinic between 1995 and 2016. Patients with nephrotic range proteinuria (UPCR ≥ 3 gram/10 mmol in 24-hours urine) and a creatinine level of ≤ 135 umol/l were included. Outcomes were progression, defined as the need for immunosuppressive therapy because of an increase of serum creatinine level of >30 % from baseline or severe persistent nephrotic syndrome, and spontaneous remission as a competing event. We fitted a Fine and Gray survival model to simultaneously predict the probabilities of progression and spontaneous remission. We included serum creatinine, UPCR and the urinary excretion of α1microglobulin as known prognostic markers, and added sequentially baseline PLA2Rab titers (ELISA) and epitope spreading. We estimated bootstrapped C-statistics and obtained calibration plots at twelve-month intervals during follow-up.

Results

We included 142 patients. Univariate comparison of progressors vs non-progressors is presented in Table 1. Neither PLA2Rab titer nor epitope spreading improved prognostic predictions when combined with known prognostic markers. The C-statistics for respectively progression and remission were between 0.71 and 0.70 at 12 and 60 months follow-up, respectively. The model was well calibrated for both progression and remission.

Conclusion

Whereas baseline PLA2Rab titer and epitope spreading predicted response to treatment in patients with MN, our data from this cohort suggest that their added value over and beyond traditional risk biomarkers for predicting spontaneous remission may be limited.

 Progressors
n=92
Non-progressors
n=50
P value
Age (years)53 ± 1352 ± 130.67
Gender (males %)64 %72 %0.36
Screatinine (µmol/l)95 [81-109]88 [81-94]0.07
UPCR (g/10 mmol)8.2 [6.0-11.17]5.8 [4.6-7.9]0.008
Uα1microglobulin (µg/min)63 [33-96]30 [20-43]<0.001
aPLA2R titer (RU/ml)126 [69-248]54 [33-147]0.03
Spreading (%)71 (77 %)33 (66 %)0.17
CR
CR and 1 epitope
CR and 2 epitopes
21 (23 %)
41 (45 %)
30 (33 %)
17 (34 %)
25 (50 %)
8 (16 %)
0.08