Less invasive test may help monitor kidney inflammation in AAV
Study measures circulating microRNAs, molecules that suppress gene activity
Measuring circulating microRNAs — short RNA molecules that ultimately suppress gene activity — could offer doctors a less invasive way to monitor glomerulonephritis, a type of kidney inflammation, in ANCA-associated vasculitis (AAV), a study found.
However, the study included a small number of patients, and testing microRNAs, or miRNAs, in the blood is still technically challenging, especially when they are present at very low levels. Larger studies are needed to confirm how useful circulating miRNAs could be as biomarkers of AAV-related glomerulonephritis (AAV-GN), researchers noted.
The study, “Circulating miRNAs correlate with clinical evaluation of activity in ANCA-associated glomerulonephritis,” was published in the European Journal of Medical Research.
Monitoring AAV activity in kidneys is especially difficult
In most cases of AAV, the immune system produces self-reactive antibodies, called ANCAs, that ultimately drive abnormal attacks against the body’s small blood vessels, causing inflammation and damage.
In the kidneys, this can cause glomerulonephritis, or inflammation of their filtering units, known as glomeruli. Over time, the kidneys may fail to remove waste and excess fluid from the blood.
It can be difficult to monitor how active the disease is, especially in the kidneys. This requires a biopsy, an invasive procedure that involves removing a small piece of tissue from the kidneys for examination under a microscope.
In this study, a team of researchers at the University of Ljubljana in Slovenia set out to look at miRNAs in the blood as less-invasive biomarkers of disease activity in people with AAV-related glomerulonephritis.
These miRNAs are tissue-specific small molecules of RNA that negatively regulate the protein production of its target genes. They do this by binding to the gene’s messenger RNA, the molecule generated from DNA that is the template for protein production.
These molecules are known to play vital roles in many important cellular processes, and the same team of researchers previously identified three circulating miRNAs as biomarkers of AAV-GN.
In this prospective study, they analyzed whether the levels of these and six other miRNAs could be used as markers of disease activity in AAV-GN.
“Accurate determination of active disease remains a significant clinical challenge,” the researchers wrote. “We sought to evaluate the utility of a circulating miRNA signature as a noninvasive biomarker for monitoring disease activity in AAV-GN.”
Lower levels of one miRNA associated with more active disease
The current study included 38 patients with a median age of 70 and a diagnosis of AAV and glomerulonephritis confirmed by a kidney biopsy. They were followed for a median of 38 months, or slightly more than three years.
Blood samples were collected at the time of the biopsy and after three, six, 12, and 24 months. Disease activity was assessed based on clinical symptoms or the standard Birmingham Vasculitis Activity Score (BVAS).
Results showed that lower blood levels of one miRNA, let-7a-5p, were significantly associated with more active disease, as assessed clinically and through the BVAS.
When comparing patients with active disease and those in complete remission, or no signs or symptoms of disease, the researchers found significant differences in the levels of let-7a-5p, miR-30b-5p, and miR-30e-5p.
Higher miR-30d-5p levels were significantly associated with higher estimated glomerular filtration rate (eGFR), a measure of kidney function, while higher miR-30d-5p levels were significantly linked to higher levels of ANCAs.
To validate the monitoring utility of the identified miRNAs and to explore their integration into decision-making algorithms, future studies in larger [patient groups] should be performed.
The levels of two miRNAs, miR-30b-5p and miR-30d-5p, showed significant changes at all time points tested relative to the initial blood sample taken at the time of the kidney biopsy. Two others, miR-181a-5p and miR-142-5p, showed significant changes in all but one time point.
“Interestingly, we detected … miR-181b-5p exclusively in follow-up, but not initial [blood] samples,” the team wrote.
There was no clear link between miRNAs levels and the amount of time that had passed since the first blood sample.
“We identified differential … patterns of miR-30 family and let-7a-5p that correlate with the presence of active disease, despite the inherent patient [variability] within the active disease category,” the researchers wrote.
In addition, patients considered to be in partial remission — with no signs or symptoms, but persistent excess protein in urine that was gradually reducing — had a miRNA signature similar to those in complete remission. This suggests their disease may no longer be active, even if their BVAS indicates otherwise.
These findings suggest that measuring circulating miRNAs alongside standard tests could help doctors get a clearer picture of how active a patient’s disease is. Using miRNAs as biomarkers could reduce the need for repeated biopsy procedures, which can be risky and uncomfortable.
Still, “to validate the monitoring utility of the identified miRNAs and to explore their integration into decision-making algorithms, future studies in larger [patient groups] should be performed,” the researchers wrote.
At the same time, “although clinical application remains distant, functional annotations of the studied miRNAs to biological pathways and target genes relevant to AAV [disease mechanisms] also support attractive therapeutic avenues,” the researchers wrote.
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