Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy

Maida Mahmud; Hans O Pinnschmidt; Linda Reinhard; Sigrid Harendza; Thorsten Wiech; Rolf A K Stahl; Elion Hoxha

doi:10.1371/journal.pone.0221293

Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy

PLoS One. 2019 Sep 9;14(9):e0221293. doi: 10.1371/journal.pone.0221293. eCollection 2019.

Authors

Maida Mahmud¹, Hans O Pinnschmidt², Linda Reinhard¹, Sigrid Harendza¹, Thorsten Wiech³, Rolf A K Stahl¹, Elion Hoxha¹

Affiliations

¹ III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
² Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³ Division of Nephropathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

Background: Membranous nephropathy (MN) is an autoimmune disease induced by circulating antibodies against the podocyte protein phospholipase A2 receptor 1 (PLA2R1-ab) in 80% of patients and represents the leading cause of nephrotic syndrome in adults. PLA2R1-ab levels correlate with disease activity and treatment response. However, their predictive role for long-term renal outcome is not clear.

Methods: The aim of this prospective observational multicenter study was to investigate the predictive role of PLA2R1-ab levels at the time of diagnosis for long-term outcome in a cohort of 243 patients with newly diagnosed biopsy-proven PLA2R1-associated MN. Statistical analyses included Cox proportional hazard models. The primary study endpoint was defined prior to data collection as doubling of serum creatinine or development of end-stage renal disease.

Results: During the median follow-up time of 48 months, 36 (15%) patients reached the study endpoint. Independent predictors for reaching the study endpoint were baseline PLA2R1-ab levels (HR = 1.36, 95%CI 1.11-1.66, p = 0.01), percentage of tubular atrophy and interstitial fibrosis (HR = 1.32, 95%CI 1.03-1.68, p = 0.03), PLA2R1-ab relapse during follow-up (HR = 3.22, 95%CI 1.36-7.60, p = 0.01), and relapse of proteinuria (HR = 2.60, 95%CI 1.17-5.79, p = 0.02). Fifty-four (22%) patients received no immunosuppressive treatment during the study, in 41 (76%) of them PLA2R1-ab spontaneously disappeared during follow-up, 29 (54%) patients had a complete remission of proteinuria, and 19 (35%) had a partial remission. Patients not treated with immunosuppression were more often females and had lower PLA2R1-ab levels, proteinuria, and serum creatinine at baseline compared to patients receiving immunosuppression. However, no conclusion on the efficacy of immunosuppressive therapies can be made, since this was not a randomized controlled study and treatment decisions were not made per-protocol.

Conclusions: PLA2R1-ab levels are, in addition to pre-existing renal damage, predictive factors for long-term outcome and should therefore be considered when deciding the treatment of patients with MN.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies / blood*
Antibodies / immunology*
Female
Glomerulonephritis, Membranous / blood
Glomerulonephritis, Membranous / diagnosis*
Glomerulonephritis, Membranous / drug therapy
Glomerulonephritis, Membranous / immunology*
Humans
Immunosuppressive Agents / therapeutic use
Male
Middle Aged
Prognosis
Receptors, Phospholipase A2 / immunology*

Substances

Antibodies
Immunosuppressive Agents
PLA2R1 protein, human
Receptors, Phospholipase A2

Grants and funding

This study was supported by a grant from the Deutsche Forschungsgemeinschaft as part of the Sonderforschungsbereich 1192 (project B1 to EH and RAKS, Project C1 to RAKS, projects B6 and CI to TW). EH is supported by the Else Kröner-Fresenius Stiftung (2016_EKES.08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.