Childrens’ Urinary MicroRNAs Predict Future Development of Heart or Kidney Diseases

MicroRNAs (miRNAs) are short, non-coding RNAs of approximately 20 nucleotides that act as post-transcriptional regulators by modifying target gene expression. Urinary miRNAs are promising biomarkers of subclinical kidney damage or dysfunction because they reflect kidney signaling and histological changes at the molecular level, enabling early detection of chronic kidney disease or progression of acute kidney injury. Urinary miRNAs are also readily obtained and are stable in stored samples.

Exosomes contain the major fraction of miRNA in urine and consequently are an ideal target to probe for molecular biomarkers of kidney diseases. Exosomes are lipid-enclosed extracellular vesicles measuring 30–150 nanometers in diameter that are released by most cells in the body and play an important role in intercellular communication by carrying bioactive molecules (soluble proteins and nucleic acids such as miRNAs) to a target cell. Exosomes in urine are primarily released from renal epithelial cells derived from renal tubular structures and hold promise as one component of a noninvasive liquid biopsy for detecting molecular changes in distinct nephron regions even in the absence of disease. Thus, the study of miRNA expression in exosomes (exo-miR) presents an opportunity in biomarker discovery for blood pressure (BP) regulation and altered renal signaling by identifying new diagnostic biomarkers and therapeutic targets.

In this light, investigators at the Mount Sinai School of Medicine (New York, NY, USA) sought to understand the relationship between urinary exo-miR expression and children's BP and estimated glomerular filtration rate (eGFR) as well as urinary sodium and potassium levels as correlates of heart and kidney health.

For this study, the investigators extracted exo-miRs from urine samples obtained from 88 healthy Mexican children aged four to six years. The study was conducted in Mexico, since children there are considered to be at much higher risk than American children for many heart and kidney problems. Differential centrifugation of spot urines enabled isolation and detection of 193 exo-miRs. Linear regression was then used to analyze the relationship between the extracted exo-miRs and children's BP, eGFR, and urine electrolyte levels.

Results revealed that three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio, and one with decreased estimated glomerular filtration rate.

"Our findings are encouraging for future studies of noninvasive indicators of kidney and heart health, especially for individuals at an increased risk of kidney dysfunction," said senior author Dr. Alison Sanders, assistant professor of environmental medicine, public health, and pediatrics at Mount Sinai School of Medicine. "Further research may discover different combinations of miRNAs that could inform early diagnosis of a wide range of kidney and cardiac diseases. So many children around the world are at risk of developing cardiorenal problems which can impact their health throughout their lives. Assessment of microRNA expression on a targeted scale could present valuable opportunities to detect and intervene with kidney disease before it can progress. That is why we are so encouraged by our team's work in this vital field."

The urinary microRNA study was published in the February 26, 2021, online edition of the journal Epigenomics.

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