title: The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin with Progression from CKD to ESRD.
abstract: Elevated levels of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are associated with negative outcomes in CKD. Our study aimed to explore the prognostic accuracy of blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for progression to ESRD, major adverse cardiovascular events, and death in a large cohort of adult patients with all-cause nondialysis-dependent CKD stages 3-5. We considered whether these factors improve prediction in relation to traditional biomarkers and clinical parameters.
  
  
  
  Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were measured on baseline plasma samples from 1982 patients who were recruited to the Chronic Renal Insufficiency Standards Implementation Study between the start of June of 2002 and the start of June of 2013. Associations with study end points were assessed using Cox regression models, receiver operator characteristic curve analyses, and reclassification statistics.
  
  
  
  Over a median follow-up of 29.5 months (interquartile range, 14.9-53.5), 21.6% of patients progressed to ESRD, 27% died, and 6.6% suffered a major adverse cardiovascular event. Higher blood levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were independently associated with a greater risk for ESRD (hazard ratio, 1.25; 95% confidence interval, 1.10 to 1.43; P<0.001 and hazard ratio, 1.35; 95% confidence interval, 1.14 to 1.59; P≤0.001, respectively, per 1 SD higher biomarker concentration). There was no association with risk for cardiovascular events or death. The addition of biomarkers to our baseline risk model of traditional clinical characteristics and laboratory parameters did not significantly improve model discrimination or risk reclassification.
  
  
  
  In patients with moderate to severe CKD, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin blood levels are independent risk factors for progression to ESRD. Additional studies are needed to establish the utility and cost-effectiveness of these novel biomarkers in the clinical setting.
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors.forename: Helen V
authors.initials: HV
authors.lastname: Alderson
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Ritchie
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland; and.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pagano
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Middleton
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Menno
authors.initials: M
authors.lastname: Pruijm
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland; and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal National Health Service Foundation Trust, Salford, United Kingdom.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kalra
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000090063:Proto-Oncogene Mas; D012372:ROC Curve; D051436:Renal Insufficiency, Chronic / Q000097:blood; D012307:Risk Factors; D020521:Stroke / Q000097:blood
chemical_list: D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas
keywords: Acute-Phase Proteins; Adult; Biomarkers; KIM-1; Kidney Failure, Chronic; LCN2 protein, human; Lipocalins; NGAL; Proto-Oncogene Proteins; ROC Curve; biomarkers; clinical outcomes; follow-up studies; humans; renal dialysis; renal insufficiency, chronic; risk factors; risk prediction