title: 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.
abstract: 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.
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Elion
authors.initials: E
authors.lastname: Hoxha
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Harendza
authors.affiliation: Institut für Medizinische Biometrie & Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Pinnschmidt
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Panzer
authors.affiliation: III. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D054507:Receptors, Phospholipase A2