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The Circular RNA Predicts Survival in Critically Ill Patients With Acute Kidney Injury


Kölling, Malte; Seeger, Harald; Haddad, George; Kistler, Andreas; Nowak, Albina; Faulhaber-Walter, Robert; Kielstein, Jan; Haller, Hermann; Fliser, Danilo; Mueller, Thomas; Wüthrich, Rudolf P; Lorenzen, Johan M (2018). The Circular RNA Predicts Survival in Critically Ill Patients With Acute Kidney Injury. Kidney International Reports, 3(5):1144-1152.

Abstract

Introduction Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They might have an impact on microRNA expression by their sponging activity. The detectability in blood of these RNA transcripts has been demonstrated in patients with cancer and cardiovascular disease. We tested the hypothesis that circulating circRNAs in blood of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy may also be dysregulated and associated with patient survival. Methods We performed a global circRNA expression analysis using RNA isolated from blood of patients with AKI as well as controls. This global screen revealed several dysregulated circRNAs in patients with AKI. Most highly increased circRNA-array-based transcripts as well as expression of the circRNA target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age-matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on maintenance hemodialysis by quantitative real-time polymerase chain reaction. Results Circulating concentrations of 3 novel circRNAs were amplified in blood of patients with AKI and in controls. (or ) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). was shown to bioinformatically sponge miR-126-5p, which was found to be highly suppressed in AKI patients and hypoxic endothelial cells. Cox regression and Kaplan-Meier curve analysis revealed as an independent predictor of 28-day survival ( < 0.01). Conclusion Circulating concentrations of circRNAs in patients with AKI are detectable. may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.

Abstract

Introduction Circular RNAs (circRNAs) have recently been described as novel noncoding regulators of gene expression. They might have an impact on microRNA expression by their sponging activity. The detectability in blood of these RNA transcripts has been demonstrated in patients with cancer and cardiovascular disease. We tested the hypothesis that circulating circRNAs in blood of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy may also be dysregulated and associated with patient survival. Methods We performed a global circRNA expression analysis using RNA isolated from blood of patients with AKI as well as controls. This global screen revealed several dysregulated circRNAs in patients with AKI. Most highly increased circRNA-array-based transcripts as well as expression of the circRNA target miR-126-5p were confirmed in blood of 109 patients with AKI, 30 age-matched healthy controls, 25 critically ill non-AKI patients, and 20 patients on maintenance hemodialysis by quantitative real-time polymerase chain reaction. Results Circulating concentrations of 3 novel circRNAs were amplified in blood of patients with AKI and in controls. (or ) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). was shown to bioinformatically sponge miR-126-5p, which was found to be highly suppressed in AKI patients and hypoxic endothelial cells. Cox regression and Kaplan-Meier curve analysis revealed as an independent predictor of 28-day survival ( < 0.01). Conclusion Circulating concentrations of circRNAs in patients with AKI are detectable. may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:September 2018
Deposited On:31 Jan 2019 10:50
Last Modified:25 Sep 2019 00:04
Publisher:Elsevier
ISSN:2468-0249
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ekir.2018.05.012
PubMed ID:30197981

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