title: Urinary DcR2 is a novel biomarker for tubulointerstitial injury in patients with diabetic nephropathy.
abstract: Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients who were diagnosed by renal biopsy. uDcR2 levels were measured by ELISA, and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2 and renal functional parameters were evaluated. Receiver operating characteristics (ROC) curve analyzed area under the curve (AUC) of uDcR2 for assessing TII. Double staining was undertaken for renal DcR2 with proximal and distal tubular markers; senescent markers p16, p21, and senescence-associated β-galactosidase (SA-β-gal); and fibrotic markers collagen I and IV. We found DcR2 was primarily expressed in renal proximal tubules; uDcR2 levels were elevated per albuminuria stratum and correlated with renal functional parameters in diabetics and were associated with percentage of tubular DcR2 and TII score in DN. The uDcR2 had an AUC of 0.909 for assessing TII in DN by ROC analysis. Almost all tubular DcR2 was coexpressed with p16 and p21, and nearly more than one-half of tubular DcR2 was positive for SA-β-gal, primarily in collagen I- and IV-positive regions of DN. Our results indicate uDcR2 could potentially serve as a novel biomarker for TII and may reflect senescence of renal proximal tubular cells in DN pathogenesis.
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ke-Hong
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Lin
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Huan-Zi
authors.initials: HZ
authors.lastname: Dai
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Kai-Long
authors.initials: KL
authors.lastname: Li
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lu-Quan
authors.initials: LQ
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Bi-Qiong
authors.initials: BQ
authors.lastname: Fu
authors.affiliation: Department of Nephrology, Daping Hospital, Third Military Medical University, Chongqing, China heynmail@163.com.
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: He
mesh_terms: D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D016922:Cellular Senescence; D024042:Collagen Type I / Q000032:analysis; D024141:Collagen Type IV / Q000032:analysis; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D053319:Tumor Necrosis Factor Decoy Receptors / Q000652:urine*; D015854:Up-Regulation; D016482:Urinalysis; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D015415:Biomarkers; C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D024042:Collagen Type I; D024141:Collagen Type IV; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D001616:beta-Galactosidase
keywords: biomarker; decoy receptor 2; diabetic nephropathy; tubulointerstitial injury