Exosomal miRNAs in Urine Associated with Children’s Cardiorenal Parameters: a Cross-Sectional Study

Abstract

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4–6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children’s cardiorenal health.

Keywords::

• adolescence
• blood pressure
• childhood
• exosome
• extracellular vesicle
• kidney
• potassium
• sodium

Author contributions

Data analysis, data interpretation and drafting of the work: Y Levin-Schwartz. Data interpretation and critical revision of the work for important intellectual content: P Curtin. Data acquisition, data interpretation and drafting of the work: D Flores. Data acquisition, data analysis, drafting of the work and critical revision of the work for important intellectual content: V N Aushev. Data acquisition and critical revision of the work for important intellectual content: M Tamayo-Ortiz. Data interpretation and critical revision of the work for important intellectual content: K Svensson. Data acquisition, data interpretation and critical revision of the work for important intellectual content: I Pantic. Data acquisition and critical revision of the work for important intellectual content: G Estrada-Gutierrez. Data acquisition and critical revision of the work for important intellectual content: M L Pizano-Zárate. Data interpretation and critical revision of the work for important intellectual content: C Gennings. Data interpretation, drafting of the work and critical revision of the work for important intellectual content: L M Satlin. Data interpretation and critical revision of the work for important intellectual content: A A Baccarelli. Data interpretation and critical revision of the work for important intellectual content: M M Tellez-Rojo. Data interpretation and critical revision of the work for important intellectual content: R O Wright. Conception of the work, data acquisition, data interpretation, drafting of the work and critical revision of the work for important intellectual content: A P Sanders.

Acknowledgments

The authors thank J Ashton and K Schooping at the University of Rochester Genomics Core for their assistance with OpenArray quantitative PCR and D Benson, W Janssen and A Sowa at the Microscopy Core at the Icahn School of Medicine at Mount Sinai for visualization and morphological characterization of extracellular vesicles. The authors also thank the ABC Medical Center in Mexico City, Mexico, for providing the research facilities necessary to complete this work. Finally, the authors thank N McRae for assistance with data curation and G M Hair for preliminary data analyses and drafting of the work.

Financial & competing interests disclosure

This work was supported in part by funding from the Mount Sinai Children’s Center Foundation and the NIH (T32HD049311, K99ES027508, R00ES027508, P30ES023515, R01ES013744, R01ES020268, P30DK079307, R24ES028522 and R01ES021357). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. Institutional review boards of the participating institutions (Icahn School of Medicine at Mount Sinai and Instituto Nacional de Salud Pública) approved this study. The women who were eligible for the PROGRESS cohort and agreed to participate signed a letter of informed consent.

Data sharing statement

Access to the data is limited because of a data sharing agreement approved by the institutional review board at Mount Sinai. However, the data from this study are accessible to qualified researchers upon reasonable request pursuant to the following restrictions to ensure the privacy of human subjects. Researchers interested in accessing PROGRESS data must send their resume or curriculum vitae and Collaborative Institutional Training Initiative training certificate to the institutional review board chair, I Wilets ([email protected]). They must also send a data analysis plan to the principal investigators for PROGRESS, RO Wright ([email protected]), M Tellez-Rojo ([email protected]) and AA Baccarelli ([email protected]). When this process is completed and the request is approved, the PROGRESS data analyst, N McRae ([email protected]), will send a de-identified dataset via the secure data sharing platform box.

Additional information

Funding

This work was supported in part by funding from the Mount Sinai Children’s Center Foundation and the NIH (T32HD049311, K99ES027508, R00ES027508, P30ES023515, R01ES013744, R01ES020268, P30DK079307, R24ES028522 and R01ES021357). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.