title: Increased urinary levels of CXCL5, CXCL8 and CXCL9 in patients with Type 2 diabetic nephropathy.
abstract: CXC chemokines are particularly significant for leukocyte infiltration in inflammatory diseases. Recent reports have shown that inflammation is one of potential pathogenic mechanisms for diabetic nephropathy. However, information on inflammation related with CXC chemokines in human Type 2 diabetic nephropathy still remains scarce. We measured urinary and serum levels of three CXC chemokines, CXCL5, CXCL8 and CXCL9, in 45 Type 2 diabetic patients (DM), 42 primary renal disease (PRD) patients and 22 healthy controls by enzyme-linked immunosorbent assay. Urinary levels of CXCL5, CXCL8 and CXCL9 in DM were significantly elevated compared to those in controls (P<.0001, P<.01, P<.001; respectively). They increased consistent with urinary albumin excretion rate (UAER) and correlated with UAER in partial correlation analyses (r=0.41, P<.01; r=0.40, P<.01; r=0.45, P<.01; respectively). Urinary levels of CXCL5 in DM were significantly interrelated to HbA(1c) (r=0.42, P<.01). On the other hand, PRD showed significant increased levels of urinary CXCL8 and CXCL9 compared to controls (P<.001, P<.01; respectively), and so did PRD as UAER increased. However, there were no significant elevations of urinary levels of CXCL5 in PRD in spite of the increased UAER. We found significant associations of UAER in DM with diabetes duration, 1/serum creatinine, urinary CXCL5 (adjusted R(2)=0.67, P<.0001) or CXCL9 (adjusted R(2)=0.69, P<.0001) in a stepwise multiple regression analysis. These results suggest that these three CXC chemokines may be involved in the progression of human Type 2 diabetic nephropathy and that CXCL5 may be of use for telling diabetic nephropathy from primary renal diseases.
authors.affiliation: Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan. waka7723@yahoo.co.jp
authors.forename: Mayumi
authors.initials: M
authors.lastname: Higurashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ohya
authors.forename: Kensuke
authors.initials: K
authors.lastname: Joh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Muraguchi
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nishimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Terawaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yagui
authors.forename: Naotake
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D054365:Chemokine CXCL5 / Q000652:urine*; D054370:Chemokine CXCL9 / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000652:urine*; D008297:Male; D008875:Middle Aged
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D054370:Chemokine CXCL9; D016209:Interleukin-8