title: Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis.
abstract: BACKGROUND
  Treatment of rheumatoid arthritis with anti-tumour necrosis factor alpha (TNFalpha) agents may lead to autoantibody formation and flares of vasculitis, but renal complications are rare.
  
  
  METHODS
  We report the clinical and pathologic findings in five patients with longstanding rheumatoid arthritis (duration of rheumatoid arthritis, 10-30 years; mean, 23 years) who developed new onset of glomerular disease after commencing therapy with anti-TNFalpha agents (duration of therapy, 3-30 months; median, 6 months).
  
  
  RESULTS
  At presentation, three patients were receiving etanercept, one adalimumab and one infliximab. Two subjects presented with acute renal insufficiency, haematuria, nephrotic-range proteinuria, positive lupus serologies, and hypocomplementemia, and renal biopsies showed proliferative lupus nephritis. Two individuals presented with new onset renal insufficiency, haematuria and proteinuria, and renal biopsies showed pauci-immune necrotizing and crescentic glomerulonephritis. One of these subjects, who had anti-myeloperoxidase autoantibodies, also developed pulmonary vasculitis. The fifth patient presented with nephrotic syndrome and renal biopsy findings of membranous glomerulonephritis, associated with immune complex renal vasculitis. A pathogenic role for anti-TNFalpha therapy is suggested by the close temporal relationship with development of glomerular disease, and by the improvement in clinical and laboratory abnormalities after drug withdrawal and initiation of immunosuppressive therapy in most cases.
  
  
  CONCLUSIONS
  Rheumatoid arthritis patients receiving anti-TNFalpha agents may develop glomerulonephritis via the induction of rheumatoid arthritis-related nephropathy or de novo autoimmune disorders.
authors.affiliation: Department of Pathology, Renal Pathology Laboratory, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. mbs2101@columbia.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Stokes
authors.forename: Kirk
authors.initials: K
authors.lastname: Foster
authors.forename: Glen S
authors.initials: GS
authors.lastname: Markowitz
authors.forename: Farhang
authors.initials: F
authors.lastname: Ebrahimi
authors.forename: William
authors.initials: W
authors.lastname: Hines
authors.forename: Darren
authors.initials: D
authors.lastname: Kaufman
authors.forename: Brooke
authors.initials: B
authors.lastname: Moore
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolde
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000068800:Etanercept; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept