title: Glomerular Pathology in Dent Disease and Its Association with Kidney Function.
abstract: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed.
  
  
  
  Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014.
  
  
  
  Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%±19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline.
  
  
  
  These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
authors.forename: Xiangling
authors.initials: X
authors.lastname: Wang
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.forename: Lada
authors.initials: L
authors.lastname: Beara-Lasic
authors.forename: Anila J
authors.initials: AJ
authors.lastname: Mehta
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Vaughan
authors.forename: Loren
authors.initials: L
authors.lastname: Herrera Hernandez
authors.forename: Andrea
authors.initials: A
authors.lastname: Cogal
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Scheinman
authors.forename: Gema
authors.initials: G
authors.lastname: Ariceta
authors.forename: Robert
authors.initials: R
authors.lastname: Isom
authors.forename: Lawrence
authors.initials: L
authors.lastname: Copelovitch
authors.forename: Felicity T
authors.initials: FT
authors.lastname: Enders
authors.forename: Dorella
authors.initials: D
authors.lastname: Del Prete
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vezzoli
authors.forename: Fabio
authors.initials: F
authors.lastname: Paglialonga
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D057973:Dent Disease / Q000473:pathology* / Q000503:physiopathology*; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007678:Kidney Glomerulus / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: Dent disease; Disease Progression; Glomerulosclerosis, Focal Segmental; Humans; Inflammation; Kidney Glomerulus; Male; Molecular Weight; Podocytes; biopsy; glomerular filtration rate; glomerulosclerosis; interstitial fibrosis; kidney; podocyte; proteinuria