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FRI0310 Serum Insulin-like Growth Factor-Binding Protein 2 (IGFBP2) as A Biomarker of Clinical and Histopathological Treatment Response in Lupus Nephritis
  1. I. Parodis1,
  2. H. Ding2,
  3. A. Zickert1,
  4. L. Arnaud1,
  5. C. Mohan2,
  6. I. Gunnarsson1
  1. 1Department of Medicine, Rheumatology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  2. 2Department of Bioengineering, University of Houston, Houston, United States


Background Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). Renal biopsy is the gold standard for evaluation of renal activity and damage in LN. Evaluation of new biomarkers for non-invasive assessment of renal pathology is warranted. Insulin-like growth factor-binding protein 2 (IGFBP2) has been found to be a robust diagnostic and prognostic biomarker in malignancies. In animal models, IGFBP2 expression was increased in anti-glomerular basement membrane (anti-GBM) glomerulonephritis and MRL/lpr lupus mice.

Objectives We aimed to investigate the role of IGFBP2 in LN.

Methods Serum levels of IGFBP2 were assessed by ELISA (R&D Systems) in 64 patients with biopsy-proven active LN (52 proliferative, 12 membranous), before and after completion of induction treatment. Post-treatment renal biopsies were performed after a median time of 7.7 months. Clinical responders (CR) were defined by ≥50% reduced proteinuria, normal or ≥25% improved estimated glomerular filtration rate (eGFR), and inactive urinary sediment. Histopathological responders (HR) were defined by ≥50% improvement of renal Activity Index (AI) in post-treatment biopsies. Long-term renal outcome after a median time of 11.3 years (range: 3.3–18.8) was determined by the last eGFR.

Results Serum IGFBP2 levels decreased following induction therapy (p<0.001). Serum IGFBP2 levels decreased in both CR (p<0.001) and HR (p<0.001), but remained unchanged in clinical non-responders (CNR; p=0.44) and histopathological non-responders (HNR; p=0.16). Post-treatment, but not baseline, IGFBP2 levels were higher in CNR compared to CR (p=0.004). Serum IGFBP2 levels correlated with proteinuria, both at baseline (r=0.34, p=0.006) and post-treatment (r=0.48, p<0.001). Post-treatment, but not baseline, IGFBP2 levels correlated with Activity Index (r=0.31, p=0.015) and Chronicity Index (CI) scores (r=0.35, p=0.006) in post-treatment renal biopsies, as well as with post-treatment SLE disease activity index 2000 (SLEDAI-2K) scores (r=0.32, p=0.009). Baseline IGFBP2 levels were associated with decreases in eGFR following treatment (p=0.028); no other association was found between baseline IGFBP2 and changes in proteinuria (p=0.14), SLEDAI-2K (p=0.97), AI scores (p=0.54) or CI scores (p=0.07). Following induction treatment, patients showed improvements in eGFR (p<0.001). No correlation was found between IGFBP2 and eGFR at either baseline or post-treatment, and there was no association between baseline (p=0.48) or post-treatment (p=0.91) serum IGFBP2 levels and changes in eGFR during long-term follow-up.

Conclusions The decreases in serum IGFBP2 levels following induction therapy in responding, but not in non-responding, patients suggest serum IGFBP2 as a marker of disease activity and response to treatment in LN. Interestingly, baseline IGFBP2 levels were associated with renal function deterioration following treatment, despite an overall improvement in eGFR. Post-treatment, but not baseline, levels mirrored both global SLE activity and histopathological findings, which together with the observed correlation with proteinuria levels suggests IGFBP2 as a marker of activity in patients with history of LN and no or low-grade proteinuria.

Disclosure of Interest None declared

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