Kidney Week

Abstract: TH-PO044

Exosomal MicroRNAs in Urine Are Associated with Children’s Blood Pressure and Renal Biomarkers: An Exploratory Cross-Sectional Study

Session Information

• AKI: Biomarkers, Drugs, Onco-Nephrology
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Sanders, Alison P., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Alison P. Sanders,

• Flores, Daniel, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Daniel Flores,

• Aushev, Vasily, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Vasily Aushev,

• Hair, Gleicy M., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Gleicy M. Hair,

• Pantic, Ivan, National Institute of Perinatology, Mexico City, Ciudad de mexico , Mexico

Ivan Pantic,

• Baccarelli, Andrea A., Columbia University, New York, New York, United States

Andrea A. Baccarelli,

• Satlin, Lisa M., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Lisa M. Satlin,

• Tellez-Rojo, Martha M., National Institute of Public Health, Cuernavaca, Mexico

Martha M. Tellez-Rojo,

• Wright, Robert O., Icahn School of Medicine at Mount Sinai, New York, New York, United States

Robert O. Wright,

• Curtin, Paul, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Paul Curtin,

Background

Urinary extracellular microRNAs are potential biomarkers of renal health and disease that may originate from epithelial cells in the renal or urogenital tract. Traditional analytical methods examine individual miRNA biomarkers; here we employ a mixtures approach to identify combinations of miRNAs associated with renal health.

Methods

We assessed the association between a mixture of exosomal miRNAs and systolic blood pressure (SBP), as well as 8 protein biomarkers measured in spot urine samples collected from 103 healthy children aged 4-5 years. We performed differential centrifugation and visualized exosomes using electron microscopy. miRNA were extracted and analyzed for 754 miRNAs using OpenArray qPCR. Expression data were normalized using the global mean. A miRNA was considered ‘detectable’ if it produced reliable qPCR signal in ≥70% of participant samples. We applied weighted quantile sum (WQS) regression to create a composite renal biomarker index of 252 ‘detectable’ miRNAs, and tested for association between the miRNA mixture with either SBP or the 8 protein biomarkers, adjusting for age, BMI, sex, and parental report of indoor smoking. We analyzed the levels of 8 proteins (albumin, cystatin C, clusterin, osteopontin (OPN), α-1-microglobulin (A1M), kidney injury molecule-1 (KIM-1), TFF (trefoil factor 3), β2-microglobulin (β2M)). We considered substantive contributors to the mixture index as those with ≥ 2% weight.

Results

Increased SBP was associated with the miRNA index (β: 0.08, 95%CI: 0.1, 1.5; p=0.02), driven by miR-590 and miR-885 (out of 13 total miRNA with weights ≥2%). Seven proteins (albumin, A1M, KIM1, TFF3, B2M and clusterin were positively associated with the miRNA mixture. Levels of cystatin C were not associated with the miRNA index. Notably, the associations of A1M, clusterin, and KIM-1 with the miRNA mixture were consistently driven by miR-574; the associations of TFF and OPN were consistently driven by miR-146b. The mRNA targets of miR-146b and miR-574 are enriched for nephrotoxic functions including renal inflammation, nephritis, tubule damage, and necrosis.

Conclusion

These findings highlight combinations of exosomal miRNAs as potential sensitive and non-invasive early life biomarkers of renal health.

Funding

• Other NIH Support