title: Pravastatin Therapy and Biomarker Changes in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease.
abstract: OBJECTIVE
  Disease-specific treatment options for autosomal dominant polycystic kidney disease are limited. Clinical intervention early in life is likely to have the greatest effect. In a 3-year randomized double-blind placebo-controlled phase 3 clinical trial, the authors recently showed that pravastatin decreased height-corrected total kidney volume (HtTKV) progression of structural kidney disease over a 3-year period. However, the underlying mechanisms have not been elucidated.
  
  
  METHODS
  Participants were recruited nationally from July 2007 through October 2009. Plasma and urine samples collected at baseline, 18 months, and 36 months from 91 pediatric patients enrolled in the above-mentioned clinical trial were subjected to mass spectrometry-based biomarker analysis. Changes in biomarkers over 3 years were compared between placebo and pravastatin-treated groups. Linear regression was used to evaluate the changes in biomarkers with the percent change in HtTKV over 3 years.
  
  
  RESULTS
  Changes in plasma concentrations of proinflammatory and oxidative stress markers (9- hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, and 15-hydroxyeicosatetraenoic acid [HETE]) over 3 years were significantly different between the placebo and pravastatin-treated groups, with the pravastatin group showing a lower rate of biomarker increase. Urinary 8-HETE, 9-HETE, and 11-HETE were positively associated with the changes in HtTKV in the pravastatin group.
  
  
  CONCLUSIONS
  Pravastatin therapy diminished the increase of cyclooxygenase- and lipoxygenase-derived plasma lipid mediators. The identified biomarkers and related molecular pathways of inflammation and endothelial dysfunction may present potential targets for monitoring of disease severity and therapeutic intervention of autosomal dominant polycystic kidney disease.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Anesthesiology, and jelena.klawitter@ucdenver.edu.
authors.forename: Jelena
authors.initials: J
authors.lastname: Klawitter
authors.affiliation: Division of Renal Diseases and Hypertension.
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.affiliation: Department of Anesthesiology, and.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Pennington
authors.affiliation: Division of Renal Diseases and Hypertension.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, and.
authors.forename: Jost
authors.initials: J
authors.lastname: Klawitter
authors.affiliation: Department of Anesthesiology, and.
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.affiliation: Division of Renal Diseases and Hypertension.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schrier
authors.affiliation: Division of Renal Diseases and Hypertension.
authors.forename: Berenice
authors.initials: B
authors.lastname: Gitomer
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Pediatrics, University of Colorado, Aurora, Colorado.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cadnapaphornchai
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000293:Adolescent; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood / Q000652:urine; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008041:Linoleic Acids / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood* / Q000188:drug therapy / Q000652:urine*; D017035:Pravastatin / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006893:Hydroxyeicosatetraenoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008041:Linoleic Acids; C024348:13-hydroxy-9,11-octadecadienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; C047628:8-hydroxyeicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D017035:Pravastatin
keywords: angiotensin-converting enzyme inhibitors; autosomal dominant polycystic kidney disease; oxidative stress; pediatric nephrology; statins