title: CD248+ stromal cells are associated with progressive chronic kidney disease.
abstract: Stromal fibroblasts are the primary cells of the kidney that produce fibrotic matrix. CD248 is a stromal marker expressed on fibroblasts and pericytes within the human kidney. Here, we tested whether CD248 expression in the kidney colocalizes with fibrosis and if it is associated with known determinants of chronic kidney disease (CKD). CD248 expression was located and quantified in situ by immunohistochemistry in kidney biopsies from 93 patients with IgA nephropathy and compared with 22 archived biopsies encompassing normal kidney tissue as control. In normal kidney tissue, CD248 was expressed by resident pericytes, stromal fibroblasts, and was upregulated in human CKD. The expression was linked to known determinants of renal progression. This relationship was maintained in a multivariate analysis with CD248 expression linked to renal survival. CD248 was expressed by a population of α-smooth muscle actin (SMA)(+) myofibroblasts and α-SMA(-) stromal cells but not expressed on CD45(+) leukocytes. Thus, CD248 defines a subset of stromal cells, including but not limited to some myofibroblasts, linked to albuminuria and tubulointerstitial damage during tissue remodeling in CKD.
authors.affiliation: Institute of Biomedical Research, University of Birmingham, Birmingham, UK. s.w.smith.1@bham.ac.uk
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Smith
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Eardley
authors.forename: Adam P
authors.initials: AP
authors.lastname: Croft
authors.forename: Joel
authors.initials: J
authors.lastname: Nwosu
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Howie
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Caroline O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000951:Antigens, Neoplasm / Q000032:analysis*; D015415:Biomarkers; D016022:Case-Control Studies; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D051379:Mice; D058628:Myofibroblasts / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology*; D017154:Stromal Cells / Q000737:chemistry* / Q000473:pathology*; D014018:Tissue Distribution
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015415:Biomarkers; C078203:CD248 protein, human