Abstract: SA-PO118

Plasma CX3CL1: A Biomarker Predicts Renal Inflammation and Progression of IgA Nephropathy

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

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

Plasma biomakers of IgA nephropathy (IGAN) are still relatively unknown to date. This study was to investigate whether CX3CL1 was associated with pathology and renal outcome in IGAN.

Methods

229 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. Renal outcome was defined as composite endpoints, including ESRD and doubling of plasma creatinine. Plasma CX3CL1 level was measured by ELISA. Inflammatory cells including CD4+, CD8+, CD20+ and CD68+ cells in renal biopsy tissues were detected by immunohistochemistry. The two single nucleotide polymorphisms (SNPs) of CX3CR1, rs3732378 and rs3732379, were assessed with IGAN leukocyte.

Results

Plasma CX3CL1 levels correlated with serum creatinine (p<0.0001, r=0.344), estimated glomerular filtration rate (eGFR) (p<0.0001, r=-0.370), albumin (p=0.0002, r=-0.249). In renal biopsy specimens, the density of CD68+ (p<0.0270, r=0.461) and CD20+ (p<0.0014, r=0.363) cells was significantly associated with plasma CX3CL1. The study showed that mesangial hypercellularity (M1), endocapillary hypercellularity (E1), tubular atrophy/interstitial fibrosis (T2) according to the Oxford classification were associated with the levels of CX3CL1. ROC curve showed that plasma CX3CL1 had a predictive value for composite endpoints (cut-off CX3CL1=0.511ng/ml, AUC=0.780, sensitivity=0.818, specificity=0.693). Higher CX3CL1 predicted worse renal outcome during follow-up (Log rank, p=0.0016) by Kaplan-Meier analysis. In multivariate Cox proportional hazard analysis, CX3CL1 levels at the time of renal biopsy was found to be an independent predictor of composite endpoints after adjustment for age, gender, mean arterial blood pressure, prior tonsillectomy (per 1% increase, hazard ratio=27.94, 95% confidence interval=2.06-374.74, p=0.012). The haplotype frequency of rs3732378 and rs3732379 was 5.43% and 5.88%. There was no association of plasma CX3CL1 with these genotypes. Neither of the SNPs was associated with composite endpoints.

Conclusion

Plasma CX3CL1 correlates with IGAN pathology and prognosis. CX3CL1 may be a risk factor for progression of IGAN.