Development of glomerulonephritis during anti-TNF-α therapy for rheumatoid arthritis

• Published in: Nephrology, dialysis, transplantation Vol. 20; no. 7; pp. 1400 - 1406
• Main Authors: Stokes, Michael B., Foster, Kirk, Markowitz, Glen S., Ebrahimi, Farhang, Hines, William, Kaufman, Darren, Moore, Brooke, Wolde, Daniel, D'Agati, Vivette D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2005; Oxford Publishing Limited (England)
• Subjects: Adalimumab; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Emergency and intensive care: renal failure. Dialysis management; Etanercept; Female; Glomerulonephritis; Glomerulonephritis - chemically induced; Glomerulonephritis - genetics; Glomerulonephritis - pathology; Humans; Immunoglobulin G - adverse effects; Infliximab; Intensive care medicine; lupus; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pharmacology. Drug treatments; Receptors, Tumor Necrosis Factor; TNFα; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Glomerulonephritis; Skin disease; Hemodialysis; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Monoclonal antibody; Extrarenal dialysis; Etanercept; Infliximab; Anticytokine; Antagonist; Recombinant protein; Fusion protein; Tumor necrosis factor α; Kidney disease; Lupus; Urinary system disease; Immunomodulator; Chronic; TNFa; Treatment; Rheumatoid arthritis; Renal failure; Immunosuppressive agent; Adalimumab
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh832

Background. Treatment of rheumatoid arthritis with anti-tumour necrosis factor alpha (TNFα) 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-TNFα 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-TNFα 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-TNFα agents may develop glomerulonephritis via the induction of rheumatoid arthritis-related nephropathy or de novo autoimmune disorders.