title: Association of Perioperative Plasma Neutrophil Gelatinase-Associated Lipocalin Levels with 3-Year Mortality after Cardiac Surgery: A Prospective Observational Cohort Study.
abstract: BACKGROUND
  Higher levels of plasma neutrophil gelatinase-associated lipocalin (pNGAL) are an early marker of acute kidney injury and are associated with increased risk of short-term adverse outcomes. The independent association between pNGAL and long-term mortality is unknown.
  
  
  METHODS
  In this prospective observational cohort study, we studied 1191 adults who underwent cardiac surgery between 2007 and 2009 at 6 centers in the TRIBE-AKI cohort. We measured the pNGAL on the pre-operative and first 3 post-operative days and assessed the relationship of peri-operative pNGAL concentrations with all-cause mortality.
  
  
  RESULTS
  During a median follow-up of 3.0 years, 139 participants died (50/1000 person-years). Pre-operative levels of pNGAL were associated with 3-year mortality (unadjusted HR 1.96, 95% CI 1.34,2.85) and the association persisted after adjustment for pre-operative variables including estimated glomerular filtration rate (adjusted HR 1.48, 95% CI 1.04-2.12). After adjustment for pre- and intra-operative variables, including pre-operative NGAL levels, the highest tertiles of first post-operative and peak post-operative pNGAL were also independently associated with 3-year mortality risk (adjusted HR 1.31, 95% CI 1.0-1.7 and adjusted HR 1.78, 95% CI 1.2-2.7, respectively). However, after adjustment for peri-operative changes in serum creatinine, there was no longer an independent association between the first post-operative and peak post-operative pNGAL and long-term mortality (adjusted HR 0.98,95% CI 0.79-1.2 for first pNGAL and adjusted HR 1.19, 95% CI 0.87-1.61 for peak pNGAL).
  
  
  CONCLUSIONS
  Pre-operative pNGAL levels were independently associated with 3-year mortality after cardiac surgery. While post-operative pNGAL levels were also associated with 3-year mortality, this relationship was not independent of changes in serum creatinine. These findings suggest that while pre-operative pNGAL adds prognostic value for mortality beyond routinely available serum creatinine, post-operative pNGAL measurements may not be as useful for this purpose.
authors.affiliation: Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; VA CT Healthcare System, West Haven, Connecticut, United States of America; Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Moledina
authors.affiliation: Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; VA CT Healthcare System, West Haven, Connecticut, United States of America; Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.affiliation: Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.affiliation: Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Thiessen-Philbrook
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.affiliation: Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Division of General Internal Medicine, San Francisco VA Medical Center, University of California, San Francisco, California, United States of America.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; VA CT Healthcare System, West Haven, Connecticut, United States of America; Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Coca
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D000209:Acute-Phase Proteins; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002423:Cause of Death; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D059035:Perioperative Period; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine