Abstract: SA-PO579
DCR2, a Cellular Senescent Molecule, Is a Novel Marker for Assessing Tubulointerstitial Fibrosis in Patients with Immunoglobulin A Nephropathy
Session Information
- Glomerular Diseases: Fibrosis, Extracellular Matrix
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Chen, Jia, Daping hospital, Chongqing, Chongqing, China
- He, Yani, Daping hospital, Chongqing, Chongqing, China
Background
DcR2 is a senescent marker expressed exclusively in senescent tubular epithelia. We calculated the ratio of urinary levels of Dcr2 to creatinine (uDcr2/Cr) and renal tissue DcR2 levels, in order to analyze the relationship between DcR2 levels and the severity of tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN).
Methods
This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with senescent (interleukin-6 [IL-6], tissue inhibitors of metalloproteinase [TIMP]-2) and fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) were analyzed by confocal microscopy. We examined the relationship among uDcR2/Cr levels, renal function, and pathological findings, using the area under the curve (AUC) approach to predict tubulointerstitial fibrosis.
Results
Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stage 1-2 chronic kidney disease (CKD) and T0 was highest among those with uDcR2/Cr < 130 ng/g. In contrast, the majority of those with uDcR2/Cr > 201 ng/g had stage 4-5 CKD and T2. Levels of uDcR2 were positively associated with urinary albumin/creatinine ratio (ACR), N-acetyl-β-D-glucosaminidase (uNAG)/Cr, and TIF scores. Levels of uDcR2 were negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0% and 80.5%, respectively. Renal DcR2 co-expressed with IL-6 and TIMP-2 in tubules and co-localized with α-SMA and collagen III in the kidneys of IgAN patients.
Conclusion
Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting chronic TIF in IgAN patients.
Funding
- Government Support - Non-U.S.