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Abstract: TH-PO997

Phospholipase A2 Receptor 1 Antibody Levels at the Time of Diagnosis Determine Renal Outcome in Patients with Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Mahmud, Maida, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Pinnschmidt, Hans O., University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Reinhard, Linda, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Harendza, Sigrid, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Wiech, Thorsten, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Stahl, Rolf A., III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Hoxha, Elion, III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Background

Membranous nephropathy (MN) is an autoimmune disease caused by circulating antibodies against the podocyte protein phospholipase A2 receptor 1 (PLA2R1-ab) in 80% of cases. PLA2R1-ab levels correlate with disease activity and treatment response. However, their significance on long-term renal outcome is not clear.

Methods

In this prospective observational multicenter study we investigated the predictive role of PLA2R1-ab levels for long-term renal outcome in 243 patients with newly diagnosed, biopsy-proven PLA2R1-associated MN, who had received no immunosuppressive treatment prior to study enrollment. The median follow-up time was 48 months. The primary endpoint was defined as doubling of serum creatinine or development of end-stage renal disease. PLA2R1-ab levels, proteinuria and serum creatinine were prospectively measured every three months.

Results

243 patients (171, 70% males; median age 55 years, IQR: 43–66 years) were included in the study. Thirty-six (15%) of the 243 patients reached the study endpoint. Multivariate Cox regression analyses adjusting for all clinical relevant parameters revealed that the following independent predictors significantly increased the risk for reaching the study endpoint: PLA2R1-ab levels (HR=1.36, 95%CI 1.11–1.66, p=0.003), percentage of tubular atrophy and interstitial fibrosis in the biopsy (HR=1.32, 95%CI 1.03–1.68, p=0.030), relapse of PLA2R1-ab during follow-up (HR=3.22, 95%CI 1.36–7.60, p=0.008), and relapse of proteinuria (HR=2.60, 95%CI 1.17–5.79, p=0.019). Fifty-four (22%) patients received no immunosuppressive treatment during the study. In 41 (76%) of these patients PLA2R1-ab spontaneously disappeared during the follow-up, 29 (54%) of them had a complete remission of proteinuria, and 19 (35%) a partial remission. Patients who were not treated with immunosuppressives were more often female and had lower PLA2R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression.

Conclusion

PLA2R1-ab levels are, in addition to pre-existing renal damage, a predictive factor for long-term outcome in patients with MN and should be considered when deciding on treatment of these patients.

Funding

  • Government Support - Non-U.S.