title: Human miRNome profiling identifies microRNAs differentially present in the urine after kidney injury.
abstract: BACKGROUND
  Extracellular microRNAs (miRNAs) have been proposed as potentially robust and stable biomarkers of various disease conditions. The primary objective of this study was to identify miRNAs differentially occurring in the urine that could serve as potential biomarkers of acute kidney injury (AKI), because traditional AKI markers have limitations with respect to sensitivity, specificity, and timeliness of diagnosis.
  
  
  METHODS
  We profiled 1809 miRNAs in pooled urine samples from 6 patients with AKI and from 6 healthy controls. We measured the 378 stably detectable miRNAs in the 12 samples individually and selected the top 7 miRNAs that were most different in the urine of patients with AKI compared with the non-AKI control individuals. These miRNAs were assessed in a larger cohort of patients with AKI (n = 98: 71 AKI patients in the intensive care unit (ICU) and 27 kidney transplantation patients with biopsy-proven tubular injury) and patients without AKI (n = 97: 74 healthy volunteers and 23 ICU patients without AKI).
  
  
  RESULTS
  We identified 4 miRNAs capable of significantly differentiating patients with AKI from individuals without AKI: miR-21 (P = 0.0005), miR-200c (P < 0.0001), miR-423 (P = 0.001), and miR-4640 (P = 0.0355). The combined cross-validated area under the ROC curve for these 4 miRNAs was 0.91. The imprecision with respect to miRNA isolation and reverse transcription efficiency was <9% across 224 samples.
  
  
  CONCLUSIONS
  In this study we determined the entire miRNome of human urine and identified a panel of miRNAs that are both detectable noninvasively and diagnostically sensitive indicators of kidney damage.
authors.affiliation: Renal Division, Department of Medicine, and.
authors.forename: Krithika
authors.initials: K
authors.lastname: Ramachandran
authors.forename: Janani
authors.initials: J
authors.lastname: Saikumar
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bijol
authors.forename: Jay L
authors.initials: JL
authors.lastname: Koyner
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Vishal S
authors.initials: VS
authors.lastname: Vaidya
mesh_terms: D058186:Acute Kidney Injury / Q000652:urine*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*
chemical_list: D035683:MicroRNAs