title: Urinary biomarkers at early ADPKD disease stage.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.
  
  
  METHODS
  ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.
  
  
  RESULTS
  In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.
  
  
  CONCLUSIONS
  UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage.
authors: Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland.
authors: Katja
authors: K
authors: Petzold
authors: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Diane
authors: D
authors: Poster
authors: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Fabienne
authors: F
authors: Krauer
authors: Institute of Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland.
authors: Katharina
authors: K
authors: Spanaus
authors: Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.
authors: Gustav
authors: G
authors: Andreisek
authors: Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.
authors: Thi Dan Linh
authors: TD
authors: Nguyen-Kim
authors: Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland.
authors: Ivana
authors: I
authors: Pavik
authors: Division of Nephrology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium.
authors: Thien Anh
authors: TA
authors: Ho
authors: Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; Division of Nephrology, University Hospital Zurich, Zurich, Switzerland; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland; Trancyst FP7-PEOPLE-MCA-ITN no. 317246, University of Zurich, Zurich, Switzerland.
authors: Andreas L
authors: AL
authors: Serra
authors: Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland; Trancyst FP7-PEOPLE-MCA-ITN no. 317246, University of Zurich, Zurich, Switzerland.
authors: Laura
authors: L
authors: Rotar
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D015331:Cohort Studies; D003710:Demography; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D009929:Organ Size; D016891:Polycystic Kidney, Autosomal Dominant / Q000473:pathology* / Q000503:physiopathology / Q000652:urine*; D012044:Regression Analysis
chemical_list: D015415:Biomarkers