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FRI0295 Urinary tweak predicts renal disease activity in patients with systemic lupus erythematosus over a 1 year period
  1. N. Wisniacki1,
  2. C. Stebbins2,
  3. J. Bienkowska3,
  4. S. Gawlak2,
  5. D. Bennett4,
  6. Y. Xiang2,
  7. A. Dearth2,
  8. A. Ranger2,
  9. L. Burkly5,
  10. M. Petri6
  1. 1Immunology Clinical Development, BIOGEN IDEC, London, United Kingdom
  2. 2Translational Medicine
  3. 3Biomedical Informatics
  4. 4Biostatistics
  5. 5Immunology Research, BIOGEN IDEC, Cambridge, MA
  6. 6Rheumatology, John Hopkins University, Baltimore, MD, United States

Abstract

Background TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily that signals through its distinct, highly inducible receptor, FGF-inducible molecule 14 (Fn14) on renal epithelial and mesenchymal cell types. The TWEAK/Fn14 pathway mediates key pathologic processes involved in renal disease in Systemic Lupus Erythematosus (SLE) patients. Previous studies have demonstrated that lupus patients with active renal disease have higher levels of urinary TWEAK (uTWEAK) compared to lupus patients with non-active renal disease.

Objectives The aim of this study was to explore the ability of uTWEAK levels to predict SLE renal and non-renal disease activity in the subsequent year after measurement

Methods The SPARE study is a prospective, longitudinal, observational study conducted at the Hopkins Lupus Center. Consecutive adult patients attending the SLE clinic were eligible if they were aged 18–75 years and met the ACR Criteria for SLE. Patients were treated according to standard clinical practice and underwent clinical laboratory and biomarker assessments for 2 years. The current analysis includes data from the first 12 months of follow up. uTWEAK levels were normalised by urinary creatinine and patients were divided into quartiles (q) according to their uTWEAK levels at baseline.

Results A total of 292 patients were included in the analysis: 92% were female; 59% were Caucasian and 34% were African American. The mean age was 46.0 (±12) years at baseline. Patients in the highest quartile of uTWEAK were more likely to have Renal SLEDAI ≥4, uPCR >0.5, Physician Global Assessment (PGA) >1 and Complement C3 <79 mg/dl at baseline (p=0.05, 0.06, 0.05 and 0.06 respectively). There was no difference in the non-renal SLEDAI score, levels of ds-DNA and C4. Patients in the highest quartile of uTWEAK at baseline were more likely to suffer a renal flare within 12 months follow up (q1 4% / q2=11% / q3= 11%/ q4=16% p=0.12). Conversely, there was no difference in the incidence of non-renal flares between the groups (q1=26% /q2=26% /q3=21%/q4=31% p=0.54). In addition, patients in the medium-high and high quartiles of uTWEAK at baseline were associated with higher renal disease activity but not non-renal SLE disease activity over the subsequent year (Table 1). Table 1. Number of patients and percentage of total visits with disease activity by uTWEAK over the subsequent year

Conclusions uTWEAK levels are associated with the same-day renal disease activity and with renal disease activity over a year of follow up in patients with SLE

Disclosure of Interest: N. Wisniacki Shareholder of: Biogen Idec, Employee of: Biogen Idec, C. Stebbins Shareholder of: Biogen Idec, Employee of: Biogen Idec, J. Bienkowska Shareholder of: Biogen Idec, Employee of: Biogen Idec, S. Gawlak Shareholder of: Biogen Idec, Employee of: Biogen Idec, D. Bennett Shareholder of: Biogen Idec, Employee of: Biogen Idec, Y. Xiang Shareholder of: Biogen Idec, Employee of: Biogen Idec, A. Dearth Shareholder of: Biogen Idec, Employee of: Biogen Idec, A. Ranger Shareholder of: Biogen Idec, Employee of: Biogen Idec, L. Burkly Shareholder of: Biogen Idec, Employee of: Biogen Idec, M. Petri Grant/research support from: Biogen Idec, Consultant for: Biogen Idec

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