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Abstract: TH-PO436

Smoldering Pauci-Immune Glomerulonephritis Associated With Recent Tofacitinib Induction in a Patient With Rheumatoid Arthritis

Session Information

Category: Glomerular Diseases

  • 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Neinast, Michael B., Southern Illinois University School of Medicine, Springfield, Illinois, United States
  • Chen, Xueguang (Gary), Southern Illinois University School of Medicine, Springfield, Illinois, United States
Introduction

Pauci-immune glomerulonephritis is typically associated with rapidly progressive glomerulonephritis. Roughly 90% of cases involve circulating levels of ANCA antibodies associated with systemic vasculitis. We present a case of smoldering glomerulonephritis diagnosed after recent initiation of tofacitinib, a Janus kinase (JAK) inhibitor, for rheumatoid arthritis.

Case Description

35-year-old female with seronegative rheumatoid arthritis (RA) was started on tofacitinib for increased flares associated with methotrexate discontinuation for pregnancy planning. Labs obtained prior to initiation included ANA, dsDNA antibodies, and anti-Smith antibodies, were negative.
Her symptoms improved however kidney function began to decline. After eight months of treatment, her creatinine increased from 1.1 g/dL with eGFR 60 to 1.22 with eGFR of 50, prompting referral to nephrology. A broad workup was thus obtained. ANA and dsDNA were both positive at 1:320 in homogenous pattern and 50 IU (low positive), respectively. UA showed microscopic hematuria with 3-5 RBCs/hpf with dysmorphia. Anti-MPO was equivocal at 20 AU/mL. Anti-PR3 was negative at 3 AU/mL (normal <19; positive >26). Anti-GBM antibodies were negative. On follow up two weeks later, her creatinine had increased to 1.31 with eGFR 46. Renal biopsy was pursued to rule out lupus nephritis.
Renal biopsy revealed sclerosing glomerulonephritis with 60% glomeruli affected, most consistent with pauci-immune type with accompanying mild interstitial fibrosis and tubular atrophy. The patient was started on high dose prednisone and weekly rituximab infusions for four weeks. Prednisone was tapered over three months until discontinued. Her renal function improved over the treatment course and stabilized at her pre-treatment level of creatinine 1.1 g/dL with eGFR 67. Rituximab infusions were continued every six months for maintenance suppression of vasculitis.

Discussion

This case raises the concern of a novel adverse event of tofacitinib given new auto-Abs and worsening renal function. There have not been any GN associations with this drug class in the literature though interestingly, tofacitinib has been trialed in treatment of giant cell arteritis with some success. More research is required for further clarification.