PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system

PLoS One. 2014 Oct 14;9(10):e110681. doi: 10.1371/journal.pone.0110681. eCollection 2014.


Patients with primary membranous nephropathy (MN) who experience spontaneous remission of proteinuria generally have an excellent outcome without need of immunosuppressive therapy. It is, however, unclear whether non-nephrotic proteinuria at the time of diagnosis is also associated with good prognosis since a reasonable number of these patients develop nephrotic syndrome despite blockade of the renin-angiotensin system. No clinical or laboratory parameters are available, which allow the assessment of risk for development of nephrotic proteinuria. Phospholipase A2 Receptor antibodies (PLA2R-Ab) play a prominent role in the pathogenesis of primary MN and are associated with persistence of nephrotic proteinuria. In this study we analysed whether PLA2R-Ab levels might predict development of nephrotic syndrome and the clinical outcome in 33 patients with biopsy-proven primary MN and non-nephrotic proteinuria under treatment with blockers of the renin-angiotensin system. PLA2R-Ab levels, proteinuria and serum creatinine were measured every three months. Nephrotic-range proteinuria developed in 18 (55%) patients. At study start (1.2±1.5 months after renal biopsy and time of diagnosis), 16 (48%) patients were positive for PLA2R-Ab. A multivariate analysis showed that PLA2R-Ab levels were associated with an increased risk for development of nephrotic proteinuria (HR = 3.66; 95%CI: 1.39-9.64; p = 0.009). Immunosuppressive therapy was initiated more frequently in PLA2R-Ab positive patients (13 of 16 patients, 81%) compared to PLA2R-Ab negative patients (2 of 17 patients, 12%). PLA2R-Ab levels are associated with higher risk for development of nephrotic-range proteinuria in this cohort of non-nephrotic patients at the time of diagnosis and should be closely monitored in the clinical management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Autoantibodies / immunology*
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology*
  • Glomerulonephritis, Membranous / mortality
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Proteinuria / diagnosis
  • Proteinuria / drug therapy*
  • Proteinuria / immunology*
  • Proteinuria / mortality
  • Receptors, Phospholipase A2 / immunology*
  • Renin-Angiotensin System / drug effects
  • Risk Factors
  • Treatment Outcome


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Autoantibodies
  • Immunosuppressive Agents
  • Receptors, Phospholipase A2

Grant support

This work is supported by a grant from the Else-Kroener-Fresenius Stiftung to R.S. and the “Deutsche Forschungsgemeinschaft” KFO 228 (Z project (E.H.) and STA193/9-1 and STA193/9-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.