Dataset Information

The Circular RNA ciRs-126 Predicts Survival in Critically Ill Patients With Acute Kidney Injury.

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. Circular RNA sponge of miR-126 (or ciRs-126) was most highly altered compared to healthy controls and disease controls (fold change of 52.1). ciRs-126 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 ciRs-126 as an independent predictor of 28-day survival (P < 0.01).

Conclusion

Circulating concentrations of circRNAs in patients with AKI are detectable. ciRs-126 may potentially sponge miR-126-5p and acts as a predictor of mortality in this patient cohort.

SUBMITTER: Kolling M

PROVIDER: S-EPMC6127441 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Circular RNA <i>ciRs-126</i> Predicts Survival in Critically Ill Patients With Acute Kidney Injury.

Kölling Malte M Seeger Harald H Haddad George G Kistler Andreas A Nowak Albina A Faulhaber-Walter Robert R Kielstein Jan J Haller Hermann H Fliser Danilo D Mueller Thomas T Wüthrich Rudolf P RP Lorenzen Johan M JM

Kidney international reports 20180602 5

<h4>Introduction</h4>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 ...[more]

PMID: 30197981

Similar Datasets

Project description:BackgroundThe progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children.ObjectivesWe aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge.DesignRetrospective cohort study using chart collection and administrative data.SettingTwo-center study in Montreal, Canada.PatientsChildren (?18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease.MeasurementsAcute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ?1 CKD diagnostic code or ?1 CKD-specific medication prescription.MethodsChart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association.ResultsA total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (P < .001).LimitationsResults may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further.ConclusionsAcute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.