title: Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury.
abstract: BACKGROUND
  Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating gene expression. Intriguingly, these RNA transcripts are detectable and stable in the blood of patients with cancer and cardiovascular disease. We tested whether circulating lncRNAs in plasma of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy were deregulated and might predict survival.
  
  
  METHODS
  We performed a global lncRNA expression analysis using RNA isolated from plasma of patients with AKI, healthy controls, and ischemic disease controls. This global screen revealed several deregulated lncRNAs in plasma samples of patients with AKI. lncRNA-array-based alterations were confirmed in kidney biopsies of patients as well as in plasma of 109 patients with AKI, 30 age-matched healthy controls, and 30 disease controls by quantitative real-time PCR.
  
  
  RESULTS
  Circulating concentrations of the novel intronic antisense lncRNA TrAnscript Predicting Survival in AKI (TapSAKI) (P < 0.0001) were detectable in kidney biopsies and upregulated in plasma of patients with AKI. Cox regression and Kaplan-Meier curve analysis revealed TapSAKI as an independent predictor of 28-day survival (P < 0.01). TapSAKI was enriched in tubular epithelial cells subjected to ATP depletion (P = 0.03).
  
  
  CONCLUSIONS
  The alteration of circulating concentrations of lncRNAs in patients with AKI supports TapSAKI as a predictor of mortality in this patient cohort.
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany; lorenzen.johan@mh-hannover.de thum.thomas@mh-hannover.de.
authors.forename: Johan M
authors.initials: JM
authors.lastname: Lorenzen
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Celina
authors.initials: C
authors.lastname: Schauerte
authors.affiliation: Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Anika
authors.initials: A
authors.lastname: Hübner
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martino
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Jan
authors.initials: J
authors.lastname: Fiedler
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Shashi K
authors.initials: SK
authors.lastname: Gupta
authors.affiliation: Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;
authors.forename: Robert
authors.initials: R
authors.lastname: Faulhaber-Walter
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and.
authors.forename: Regalla
authors.initials: R
authors.lastname: Kumarswamy
authors.affiliation: Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;
authors.forename: Carsten
authors.initials: C
authors.lastname: Hafer
authors.affiliation: Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.affiliation: Saarland University Medical Centre, Homburg/Saar, Germany;
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and National Heart and Lung Institute, Imperial College London, London, UK. lorenzen.johan@mh-hannover.de thum.thomas@mh-hannover.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000235:genetics* / Q000401:mortality; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D062085:RNA, Long Noncoding / Q000097:blood* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D062085:RNA, Long Noncoding