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Abstract: TH-PO1010

Plasma CXCL16: A Biomarker Predicts Renal Inflammation and Progression of IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Luo, Ran, Tongji Hospital, Tongji Medical College, Huazhong Univ of Science and Technology, Wuhan, China
  • Ge, Shuwang, Tongji Hospital, Tongji Medical College, Huazhong Univ of Science and Technology, Wuhan, China
  • Xu, Gang, Tongji Hospital, Tongji Medical College, Huazhong Univ of Science and Technology, Wuhan, China
Background

Noninvasive biomarkers associated with IGAN prognosis are urgently needed for clinical practice. This study was to investigate whether CXCL16 was associated with pathology and renal outcome in IGAN.

Methods

230 patients with IGAN diagnosed by renal biopsy between 2012 and 2014 at Huazhong University of Science and Technology Tongji hospital, were included in the study. Follow-up time was up to 42.5 months. The renal outcome was defined as composite endpoints, including ESRD and doubling of plasma creatinine. Plasma CXCL16 level was measured by ELISA. Inflammatory cells including CD4+, CD8+, CD20+ and CD68+ cells in renal biopsy tissues and renal CXCL16 expression were detected by immunohistochemistry.

Results

Plasma CXCL16 levels correlated with serum creatinine (p< 0.0001, r=0.362), estimated glomerular filtration rate (p< 0.0001, r=-0.411), albumin (p=0.0019, r=-0.2068). In renal biopsy specimens, the density of CD8+, CD4+, and CD20+ cells were significantly associated with plasma CXCL16 levels. Mesangial hypercellularity and tubular atrophy/interstitial fibrosis according to the Oxford classification were associated with the plasma levels of CXCL16. ROC curve showed that plasma CXCL16 levels had a predictive value for composite endpoints (cut-off CXCL16=2.968ng/ml, AUC=0.593, sensitivity=0.611, specificity=0.618). Higher plasma CXCL16 levels predicted worse renal outcome during follow-up (Log-rank, p=0.006) by Kaplan-Meier analysis. In multivariate Cox proportional hazard analysis, plasma CXCL16 levels at the time of renal biopsy were found to be an independent predictor of composite endpoints after adjustment for age, gender, mean arterial blood pressure and serum albumin (p= 0.012). Immunofluorescence results showed that the receptor CXCR6 was expressed in renal CD8+ T cells, not in CD4+ T cells. plasma CXCL16 levels were positively associated with renal CXCL16 expression in tissues (r = 0.316, p=0.018). In vitro, IFN-γ promoted CXCL16 expression in HK2 cells through NF-κB pathway. CXCL16 had a chemotactic effect on Jurkat T cells and directly acted on NRK-49F cells to promote fibrosis.

Conclusion

Plasma CXCL16 levels correlate with IGAN pathology and prognosis. CXCL16 may be a risk factor for progression of IGAN.