title: MicroRNAs relate to early worsening of renal function in patients with acute heart failure.
abstract: BACKGROUND
  Deregulation of microRNAs (miRNAs) may be involved in the pathogenesis of heart failure (HF) and renal disease. Our aim is to describe miRNA levels related to early worsening renal function in acute HF patients.
  
  
  RESULTS
  We studied the association between 12 circulating miRNAs and Worsening Renal Function (WRF; defined as an increase in the serum creatinine level of 0.3mg per deciliter or more from admission to day 3), absolute change in creatinine and Neutrophil Gelatinase Associated Lipocalin (NGAL) from admission to day 3 in 98 patients hospitalized for acute HF. At baseline, circulating levels of all miRNAs were lower in patients with WRF, with statistically significant decreased levels of miR-199a-3p, miR-423-3p, and miR-let-7i-5p (p-value<0.05). The increase in creatinine during the first 3 days of hospitalization was significantly associated with lower levels of miR-199a-3p, miR-27a-3p, miR-652-3p, miR-423-5p, and miR-let-7i-5p, while the increase in NGAL was significantly associated with lower levels of miR-18a-5p, miR-106a-5p, miR-223-3p, miR-199a-3p and miR-423-3p. MiR-199a-3p was the strongest predictor of WRF, with an Odds Ratio of 1.48 (1.061-2.065; p-value=0.021) and a C-index of 0.701.
  
  
  CONCLUSIONS
  Our results show that the levels of circulating miRNAs at hospital admission for acute HF were consistently lower in patients who developed worsening of renal function. MiR-199a-3p was the best predictor of WRF in these patients.
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Noemi
authors.initials: N
authors.lastname: Bruno
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jozine M
authors.initials: JM
authors.lastname: ter Maaten
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Ovchinnikova
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Eline L
authors.initials: EL
authors.lastname: Vegter
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Mattia A E
authors.initials: MA
authors.lastname: Valente
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Momentum Research, Inc., Allschwil, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schmitter
authors.affiliation: Department of Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Medical University, Clinical Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: University of California at San Francisco, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Cotter
authors.affiliation: Momentum Research, Durham, NC, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Davison
authors.affiliation: National Heart & Lung Institute, Royal Brompton & Harefield Hospitals, Imperial College, London, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Merck Research Laboratories, Rahway, NJ, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bloomfield
authors.affiliation: University of Iowa Carver College of Medicine Cardiovascular Research Center, Iowa City, IA, USA.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Dittrich
authors.affiliation: University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Eugene
authors.initials: E
authors.lastname: Berezikov
authors.affiliation: University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: a.a.voors@umcg.nl.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000378:metabolism*; D018450:Disease Progression; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D051437:Renal Insufficiency / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D012189:Retrospective Studies; D014970:Xanthines / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D004232:Diuretics; D035683:MicroRNAs; D014970:Xanthines; C073525:rolofylline; D003404:Creatinine
keywords: Acute heart failure; Circulating microRNA; Worsening renal function