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Abstract: FR-PO854

Serum Biomarkers of Histologic Activity in Lupus Nephritis Kidney Biopsies

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Zhang, Xiaolan, The Ohio State University, Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University, Columbus, Ohio, United States
  • Sinclair, John, The Ohio State University, Columbus, Ohio, United States
  • Nadasdy, Tibor, Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

The kidney biopsy is the gold standard for diagnosing and managing lupus nephritis (LN) but it is not practical to repeat biopsies frequently to follow disease status. Because LN is part of a systemic disease we interrogated the serum of LN patients for biopsies that could non-invasively reflect biopsy findings.

Methods

Serum was collected at the time of biopsy from 50 LN patients and from 9 healthy controls. Fifteen pro-inflammatory cytokines and immune mediators were measured using the Luminex multiplexing platform. Data were analyzed by Milliplex Analyst Version 5.1. NIH activity (AI) and chronicity (CI) indices of the LN biopsies were scored by a renal pathologist. Mild, moderate and severe acute injury were defined as AI scores of 1-4, 5-9, and >10, respectively.

Results

IL-2R, CXCL16, M-CSF, TNFR1 and VCAM-1 were increased 2.7, 1.9, 2.6, 3.4 and 2.1-fold respectively in LN compared to healthy controls (all p < 0.01). Adiponectin, NGAL and M-CSF were significantly elevated in Class IV LN compared to other classes (all p < 0.01). M-CSF and pentraxin 3 (PTX) positively correlated with AI (R2=0.46, p<0.0001; R2=0.27, p=0.0006, respectively), but none correlated with CI. With respect to the individual elements of the AI, M-CSF was elevated significantly in endocapillary proliferation (R2=0.43, p< 0.0001), wireloop formation (R2=0.29, p 0.0045), PMN infiltration (R2=0.37, p 0.0002), fibrinoid necrosis (R2=0.28, p 0.0022), and cellular crescents (R2=0.2883, p 0.0052). PTX only correlated with the fibrinoid necrosis component of AI (R2=0.22, p 0.008). The area under the receiver operating characteristic curve (AUC) for M-CSF to differentiate between mild and moderate-severe crescentic injury was 0.89 (p=0.003) and for M-CSF to differentiate mild from moderate-severe AI was 0.87 (p<0.0001). PTX differentiated between mild and moderate-severe necrosis with an AUC of 0.90 (p=0.01).

Conclusion

Serum M-CSF and PTX appear to reflect severe intra-renal injury in LN. These biomarkers may be useful in managing LN if they can be shown to decrease as crescents and necrosis resolve.

Funding

  • Other NIH Support