title: Metabolite Profiles Predict Acute Kidney Injury and Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement.
abstract: BACKGROUND
  Acute kidney injury (AKI) occurs commonly after transcatheter aortic valve replacement (TAVR) and is associated with markedly increased postoperative mortality. We previously identified plasma metabolites predictive of incident chronic kidney disease, but whether metabolite profiles can identify those at risk of AKI is unknown.
  
  
  RESULTS
  We performed liquid chromatography-mass spectrometry-based metabolite profiling on plasma from patients undergoing TAVR and subjects from the community-based Framingham Heart Study (N=2164). AKI was defined by using the Valve Academic Research Consortium-2 criteria. Of 44 patients (mean age 82±9 years, 52% female) undergoing TAVR, 22 (50%) had chronic kidney disease and 9 (20%) developed AKI. Of 85 metabolites profiled, we detected markedly concordant cross-sectional metabolic changes associated with chronic kidney disease in the hospital-based TAVR and Framingham Heart Study cohorts. Baseline levels of 5-adenosylhomocysteine predicted AKI after TAVR, despite adjustment for baseline glomerular filtration rate (odds ratio per 1-SD increase 5.97, 95% CI 1.62-22.0; P=0.007). Of the patients who had AKI, 6 (66.7%) subsequently died, compared with 3 (8.6%) deaths among those patients who did not develop AKI (P=0.0008) over a median follow-up of 7.8 months. 5-adenosylhomocysteine was predictive of all-cause mortality after TAVR (hazard ratio per 1-SD increase 2.96, 95% CI 1.33-6.58; P=0.008), independent of baseline glomerular filtration rate.
  
  
  CONCLUSIONS
  In an elderly population with severe aortic stenosis undergoing TAVR, metabolite profiling improves the prediction of AKI. Given the multifactorial nature of AKI after TAVR, metabolite profiles may identify those patients with reduced renal reserve.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA Harvard Clinical Research Institute, Boston, MA.
authors.forename: Sammy
authors.initials: S
authors.lastname: Elmariah
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Farrell
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Daher
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Xu
authors.initials: X
authors.lastname: Shi
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Keyes
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: Cain
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Pomerantsev
authors.affiliation: Department of Cardiac Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Gus J
authors.initials: GJ
authors.lastname: Vlahakes
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Inglessis
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Passeri
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Igor F
authors.initials: IF
authors.lastname: Palacios
authors.affiliation: Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA Endocrinology Division, Brigham & Women's Hospital, Boston, MA Division of Intra-mural Research, National Heart, Lung, and Blood Institute, Bethesda, MD.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Rhee
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA gerszten.robert@mgh.harvard.edu.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000401:mortality*; D002853:Chromatography, Liquid; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D013058:Mass Spectrometry; D008404:Massachusetts / Q000453:epidemiology; D055432:Metabolomics / Q000379:methods; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D012435:S-Adenosylhomocysteine
keywords: aortic stenosis; kidney; metabolomics; mortality; transcatheter aortic valve implantation