title: Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis.
abstract: BACKGROUND
  Disease monitoring of autosomal dominant polycystic kidney disease (ADPKD) will become more important with potential upcoming therapeutic interventions. Because serum creatinine level is considered of limited use and measurement of effective renal blood flow (ERBF) and total renal volume are time consuming and expensive, there is a need for other biomarkers. We aimed to investigate which urinary markers have increased levels in patients with ADPKD; whether these urinary markers are associated with measured glomerular filtration rate (mGFR), ERBF, and total renal volume; and whether these associations are independent of albuminuria (urine albumin excretion [UAE]).
  
  
  METHODS
  Diagnostic test study.
  
  
  METHODS
  102 patients with ADPKD (Ravine criteria) and 102 age- and sex-matched healthy controls.
  
  
  METHODS
  24-hour urinary excretion of glomerular (immunoglobulin G), proximal tubular (kidney injury molecule 1 [KIM-1], N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin [NGAL], and β(2)-microglobulin), and distal tubular (heart-type fatty acid binding protein [H-FABP]) damage markers and inflammatory markers (monocyte chemotactic protein 1 [MCP-1] and macrophage migration inhibitory factor).
  
  
  METHODS
  Disease severity assessed using measures of kidney function (mGFR and ERBF, measured using clearance of iothalamate labeled with iodine 125 and hippuran labeled with iodine 131 during continuous infusion, respectively) and structure (total renal volume, measured using magnetic resonance imaging).
  
  
  METHODS
  24-hour UAE.
  
  
  RESULTS
  In 102 patients with ADPKD (aged 40 ± 11 years; 58% men), levels of all measured urinary biomarkers were increased compared with healthy controls. Excretion of immunoglobulin G and albumin relatively were most increased. ERBF and mGFR values were associated with urinary excretion of β(2)-microglobulin, NGAL, and H-FABP independent of UAE, whereas total renal volume was associated with KIM-1, NGAL, and MCP-1 independent of UAE.
  
  
  CONCLUSIONS
  Cross-sectional, single center.
  
  
  CONCLUSIONS
  Levels of markers for multiple parts of the nephron are increased in patients with ADPKD. In addition to measurement of UAE, measurement of urinary β(2)-microglobulin, KIM-1, H-FABP, MCP-1, and especially NGAL could be of value for determination of disease severity in patients with ADPKD.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Boertien
authors.forename: Ferdau L
authors.initials: FL
authors.lastname: Nauta
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Mieneke
authors.initials: M
authors.lastname: Rook
authors.forename: Eric J
authors.initials: EJ
authors.lastname: van der Jagt
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Paul E
authors.initials: PE
authors.lastname: de Jong
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000209:Acute-Phase Proteins; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007074:Immunoglobulin G / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine*; D015995:Prevalence; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D012720:Severity of Illness Index; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D007074:Immunoglobulin G; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D001613:beta 2-Microglobulin; D000118:Acetylglucosaminidase