title: Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis.
abstract: BACKGROUND
  The pathogenesis of progressive renal insufficiency in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Evidence from experimental models of ADPKD suggests that elevated endothelin-1 (ET-1) drives cyst growth, renal fibrosis and loss of renal function, but whether ET-1 is elevated in humans with ADPKD is uncertain.
  
  
  METHODS
  In a cross-sectional study of ADPKD we measured urinary ET-1, a surrogate for ET-1 in kidney cortex, in spot collections corrected for creatinine. The volume of each kidney was measured using MRI-based stereology. The relationship of urine ET-1 with MDRD eGFR and kidney volume was modeled by multiple linear regression with adjustment for clinical covariates.
  
  
  RESULTS
  Patients with ADPKD were ages 18 to 53 with eGFRs (median, interquartile range) of 63.2 (43.5-80.2) ml/min/1.73 m(2) and albumin/creatinine ratios (ACR) of 115.0 (7.5-58.5) μg/mg. Urine ET-1 was inversely associated with eGFR (r = -0.480, P < 0.05) and positively (r = 0.407, P = 0.066) with ACR independent of age and female sex (P < 0.01). ET-1 appeared to be positively associated with total kidney volume (r = 0.426, P = 0.100), with a test for trend across urine ET-1 quartiles yielding z = 1.83, P = 0.068. ET-1 strongly correlated with NAGase (r = 0. 687, P = 0.001), a marker of tubular damage and a surrogate marker of renal disease progression in ADPKD. Of note, ET-1 levels in urine were not correlated with hypertension.
  
  
  CONCLUSIONS
  In a translational study of patients with ADPKD, urinary ET-1 was inversely associated with eGFR and positively correlated with total kidney volume. Taken together with results from experimental models, these findings suggest that the role of ET-1 in ADPKD warrants further investigation.
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Rainbow Babies and Children's Hospital, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Raina
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Rainbow Babies and Children's Hospital, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Lou
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Berger
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Rainbow Babies and Children's Hospital, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Vogt
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Angelique Sao-Mai
authors.initials: AS
authors.lastname: Do
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Rainbow Babies and Children's Hospital, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Cunningham
authors.affiliation: Department of Radiology, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Pauravi
authors.initials: P
authors.lastname: Vasavada
authors.affiliation: Department of Radiology, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: University Hospitals Case Medical Center, Center for Pediatric Nephrology, Cleveland Clinic Foundation, Cleveland, USA.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Dell
authors.affiliation: Department of Medicine, Division of Nephrology and Hypertension, Cleveland, USA. mss5@case.edu.|Case Western Reserve University School of Medicine, 2109 Adelbert Road, Biomedical Research Bldg. #322, Cleveland, OH, 44106, USA. mss5@case.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Simonson
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D018450:Disease Progression; D019332:Endothelin-1 / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000652:urine; D007668:Kidney / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010865:Pilot Projects; D016891:Polycystic Kidney, Autosomal Dominant / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D051437:Renal Insufficiency / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D000118:Acetylglucosaminidase