title: Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study.
abstract: BACKGROUND
  Tumour necrosis alpha has been implicated in the pathogenesis of autoimmune disorders was to evaluate the safety, tolerability and potential efficacy of the tumour necrosis factor alpha (TNF-alpha) inhibitor, etanercept (ET), in patients with idiopathic membranous nephropathy (MN).
  
  
  METHODS
  Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy.
  
  
  RESULTS
  Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-alpha, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 +/- 527 pg/ml, P = 0.028).
  
  
  CONCLUSIONS
  Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.
authors.affiliation: Department of Nephrology & Transplantation Center, Laiko Hospital, Athens, Greece. Sofia.Lionaki@gmail.com
authors.forename: Sofia
authors.initials: S
authors.lastname: Lionaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Siamopoulos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Theodorou
authors.forename: Eva
authors.initials: E
authors.lastname: Papadimitraki
authors.forename: George
authors.initials: G
authors.lastname: Bertsias
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Boumpas
authors.forename: John
authors.initials: J
authors.lastname: Boletis
mesh_terms: D000328:Adult; D000368:Aged; D000068800:Etanercept; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept