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Abstract: PO1542

Use of Urinary Proteins as Predictors of Response to Immunosuppressive Treatment in Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Androga, Lagu A., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Viehman, Jason K., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Bobart, Shane A., Cleveland Clinic Florida, Weston, Florida, United States
  • Vaughan, Lisa E., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Zand, Ladan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Greene, Eddie L., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Cattran, Daniel C., Toronto General Hospital, Toronto, Ontario, Canada
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Prognosis is defined by remission in proteinuria. Response to immunosuppression agents such as calcineurin inhibitors and rituximab vary. While the presence of anti-PLA2R antibodies may help to guide prognosis and treatment strategies, further identifying biomarkers that could refine treatment decision would be useful. Using data from the MENTOR trial (NEJM 2019), we evaluated whether 24-hour total urinary protein, urinary albumin, immunoglobulin M (uIgM), immunoglobulin G (uIgG), and urinary alpha 1 microglobulin (uα1m) at baseline could be used to predict response to immunosuppressive therapy at 12 months in patients with MN.

Methods

Logistic regression models were used to study the relationship between baseline urinary proteins with patients’ treatment outcomes by treatment drug (rituximab or cyclosporine). The treatment outcome was defined as patients achieving either complete (CR; <0.3g/24 hours) or partial remission (PR; >0.3-<3.5g/24 hours) of proteinuria at 12 months.

Results

In both cyclosporine and rituximab arm, all urinary proteins exhibited a decline from baseline to 12 months post treatment. However, none of the baseline urinary proteins were found to be significantly associated with treatment response at 12 months (p>0.05 for all). Results were similar when restricted to patients with positive anti-PLA2R at baseline.

Conclusion

Baseline measures of the urinary albumin, uIgM, uIgG, and uα1m are not predictors of patients going into CR or PR at 12 months after treatment with rituximab or cyclosporine.

Table 1: Odds ratio of urinary protein predicting CR or PR at 12 months in patients treated with Rituximab or Cyclosporine (Fully Adjusted model)
Urinary ProteinTreatment GroupAll PatientsAnti-PLA2R Antibody Positive Patients
Odds Ratio (95% CI)p-valueOdds Ratio (95% CI)p-value
α1M, per 10 mg / 24hrRituximab1.018 (0.946, 1.096)0.6311.024 (0.939, 1.117)0.591
Cyclosporine1.009 (0.950, 1.072)0.7671.006 (0.935, 1.082)0.873
Albumin, per 100 mg / 24hrRituximab0.996 (0.982, 1.011)0.5960.995 (0.978, 1.013)0.577
Cyclosporine0.992 (0.978, 1.006)0.2700.990 (0.973, 1.007)0.257
IgM, per 10 µg / 24hrRituximab1.014 (0.984, 1.045)0.3691.015 (0.983, 1.047)0.365
Cyclosporine1.012 (0.988, 1.036)0.3341.011 (0.986, 1.037)0.388
IgG, per 100 mg / 24hrRituximab0.988 (0.923, 1.057)0.7180.972 (0.901, 1.050)0.472
Cyclosporine0.958 (0.909, 1.009)0.1010.941 (0.881, 1.004)0.067

*Adjusted for adjust for age, sex, eGFR, and creatinine clearance