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Abstract: PO1541

Urine Biomarkers Predict Treatment Response in the MENTOR Study

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Pattrapornpisut, Prapa, University Health Network, Toronto, Ontario, Canada
  • Moran, Sarah Margaret, Queen's University, Kingston, Ontario, Canada
  • Bader, Gary, University of Toronto, Toronto, Ontario, Canada
  • Xu, Changjiang, University of Toronto, Toronto, Ontario, Canada
  • Boutros, Paul C., University of California Los Angeles, Los Angeles, California, United States
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada
  • Cattran, Daniel C., University Health Network, Toronto, Ontario, Canada
  • Reich, Heather N., University Health Network, Toronto, Ontario, Canada

Group or Team Name

  • for the MENTOR investigators
Background

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. The outcome of patients with MN is highly variable and clinical parameters do not reliably identify which patients will respond to immunosuppressive therapy (IS). In the MENTOR trial >40% of subjects did not achieve complete or partial remission (CR/PR) of proteinuria by 12 months despite IS with rituximab or cyclosporine, exposing them to unnecessary IS and portending potentially poor prognosis. We evaluated whether a panel of urinary molecular markers of kidney inflammation and fibrosis improves the ability to identify treatment responders in the MENTOR trial beyond clinical data alone.

Methods

We measured the abundance of 55 urinary cytokines, metalloproteases and their inhibitors at the time of randomization in 104 subjects using a Luminex-based multiplex assay. The primary outcome of interest was achievement of CR/PR at 12 months.

Results

Patients achieving CR/PR had significantly higher CrCl (94.25 +31.42 vs 75.17 + 28.52 mL/min/1.73m2, p=0.002) and lower anti-PLA2R titre (168.5 IQR 20.5,341 vs 549 IQR 115.5,1345 U/mL, p= 0.0002) at baseline. Stepwise selection identified 3 clinical variables (CrCl, PLA2R, treatment) and 8 urinary proteins (IL9, IL10, GM-CSF, VEGF-A, TGFα, MMP2, MMP3, MMP10) associated with CR/PR. A model including the clinical and molecular variables improved discrimination of patients who are predicted to achieve CR/PR compared to a model containing clinical variables alone (ANOVA test p-value = 1.30x10-5, AUC 0.81 ± 0.096 vs. 0.70 ± 0.109).

Conclusion

In summary, measurement of a panel urinary molecular markers improves the ability to predict remission at 12 months in patients with MN. Improved prediction of patients resistant to standard therapy using non-invasive markers has potential to offer more individualized treatment, to spare unnecessary treatment toxicity and to identify patients who may benefit from trials of novel therapeutic agents.