Circulating long noncoding RNATapSaki is a predictor of mortality in critically ill patients with acute kidney injury.

Autor: Lorenzen JM; 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., Schauerte C; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Kielstein JT; Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;, Hübner A; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Martino F; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Fiedler J; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Gupta SK; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Faulhaber-Walter R; Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;, Kumarswamy R; Institute of Molecular and Translational Therapeutic Strategies (IMTTS) and., Hafer C; Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;, Haller H; Department of Medicine/Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany;, Fliser D; Saarland University Medical Centre, Homburg/Saar, Germany;, Thum T; 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.
Jazyk: angličtina
Zdroj: Clinical chemistry [Clin Chem] 2015 Jan; Vol. 61 (1), pp. 191-201. Date of Electronic Publication: 2014 Oct 07.
DOI: 10.1373/clinchem.2014.230359
Abstrakt: 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.
(© 2014 American Association for Clinical Chemistry.)
Databáze: MEDLINE