title: Posterior urethral valve in fetuses: evidence for the role of inflammatory molecules.
abstract: BACKGROUND
  The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group).
  
  
  METHODS
  Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (β2)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test).
  
  
  RESULTS
  An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-β. In the correlation analysis, β2-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine.
  
  
  CONCLUSIONS
  This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.
authors.affiliation: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2° andar, sala 281, 30.130-100, Belo Horizonte, MG, Brazil.
authors.forename: Érica Leandro Marciano
authors.initials: ÉLM
authors.lastname: Vieira
authors.affiliation: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2° andar, sala 281, 30.130-100, Belo Horizonte, MG, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pessoa Rocha
authors.affiliation: Fetal Medicine Unit, Department of Gynecology and Obstetrics, UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Macedo Bastos
authors.affiliation: National Institute of Science and Technology in Molecular Medicine (INCT-MM), Faculty of Medicine, UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Kátia Daniela
authors.initials: KD
authors.lastname: da Silveira
authors.affiliation: Fetal Medicine Unit, Department of Gynecology and Obstetrics, UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Alamanda K
authors.initials: AK
authors.lastname: Pereira
authors.affiliation: Fetal Medicine Unit, Department of Gynecology and Obstetrics, UFMG, Belo Horizonte, MG, Brazil.|Pediatric Nephrology Unit, Department of Pediatrics, UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Araújo Oliveira
authors.affiliation: National Institute of Science and Technology in Molecular Medicine (INCT-MM), Faculty of Medicine, UFMG, Belo Horizonte, MG, Brazil.|Pediatric Nephrology Unit, Department of Pediatrics, UFMG, Belo Horizonte, MG, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Marques de Miranda
authors.affiliation: Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2° andar, sala 281, 30.130-100, Belo Horizonte, MG, Brazil. acssilva@hotmail.com.|Fetal Medicine Unit, Department of Gynecology and Obstetrics, UFMG, Belo Horizonte, MG, Brazil. acssilva@hotmail.com.|Pediatric Nephrology Unit, Department of Pediatrics, UFMG, Belo Horizonte, MG, Brazil. acssilva@hotmail.com.
authors.forename: Ana Cristina
authors.identifier: http://orcid.org/0000-0001-9222-3882
authors.initials: AC
authors.lastname: Simões E Silva
mesh_terms: D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D006801:Humans; D062071:Infant, Extremely Premature / Q000652:urine*; D007677:Kidney Function Tests; D008297:Male; D011247:Pregnancy; D014463:Ultrasonography; D014521:Urethra / Q000002:abnormalities* / Q000000981:diagnostic imaging; D014522:Urethral Diseases / Q000000981:diagnostic imaging / Q000652:urine*
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Biomarkers; Chronic kidney disease; Immunomodulation; Posterior urethral valve; Preterm fetus