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An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury
Nikol Sullo1, Silvia Mariani1, Maria JnTala1
1Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, United Kingdom.
Objectives:
Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 microm known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population.
Design:
Single center prospective cohort feasibility study.
Setting:
PICU.
Patients:
Twenty-four children (≤ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support.
Interventions:
None.
Measurements And Main Results:
Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6-12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling.
Conclusions:
Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury.
Insights
Microvesicles and micro-RNAs show promise as biomarkers for acute kidney injury in children undergoing cardiac surgery. These measurable signals can help identify patients at higher risk for this condition.
Area of Science:
- Biomarkers and diagnostics
- Pediatric critical care
- Renal medicine
Background:
- Acute kidney injury (AKI) is a significant concern in pediatric cardiac surgery.
- Micro-RNAs and microvesicles are emerging as potential disease-specific biomarkers.
- Feasibility of measuring these novel biomarkers alongside traditional ones in this population is unexplored.
Purpose of the Study:
- To evaluate the feasibility of measuring micro-RNAs and microvesicles as biomarkers for AKI.
- To assess other known AKI biomarkers in pediatric cardiac surgery patients.
- To explore potential correlations between these biomarkers and AKI development.
Main Methods:
- Prospective cohort feasibility study in a pediatric intensive care unit.
- Included 24 children undergoing cardiac surgery with cardiopulmonary bypass.
- Collected blood and urine samples preoperatively and postoperatively for analysis of microvesicles (flow cytometry, NanoSight) and micro-RNAs (microarray, qPCR).
Main Results:
- 14 out of 24 patients developed AKI.
- AKI patients were younger, had longer cardiopulmonary bypass times, and required more inotropic support.
- Distinct patterns of platelet and endothelial-derived microvesicles were observed preoperatively in AKI patients, with higher levels postoperatively.
- Differential expression of several micro-RNA species was noted in AKI patients.
Conclusions:
- Microvesicles and micro-RNAs expression patterns are measurable in pediatric cardiac surgery patients.
- These novel biomarkers show potential for stratifying patients at risk of developing acute kidney injury.
- Further research is warranted to validate their clinical utility.
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