A novel methodology for assessing urine extracellular vesicles (uEVs) in urine samples reveals abnormalities in the kidneys sooner than traditional methods and can also predict renal function deterioration.
A group of researchers from the University of Tokyo examined eurine samples from children with and without chronic kidney disease (CKD). They discovered that when kidney function declines, the size and composition of uEVs vary. This proof of concept might aid in the development of new urine tests that detect the disease early, as well as analogous testing for other disorders. The kidneys are the body’s primary filtration mechanism.
These bean-shaped, fist-sized organs are made up of millions of microscopic filtration units known as nephrons that work tirelessly to keep our blood clean. Unfortunately, chronic kidney disease (CKD) affects 9% of the worldwide population, and the number of cases is increasing.
When nephrons are destroyed, whether by lifestyle, genetic and congenital disorders, or injury, CKD occurs. Many patients may not experience significant symptoms and, as a result, do not seek treatment until the problem has progressed. Because it is difficult to replace injured nephrons entirely, the sooner the diagnosis, the better the prognosis.
Typically, a urine or blood test may inform doctors if a patient has kidney impairment.
These tests, however, can still miss the very early phases of nephron loss that herald the onset of CKD. Researchers at the University of Tokyo sought to see whether there were any additional early indicators of kidney disease, particularly in youngsters.
“We discovered that alterations in microscopic structures called extracellular vesicles in urine are useful in the detection of renal illness,” said Graduate School of Medicine Associate Professor Yutaka Harita. “With reduced renal function, the fraction of bigger vesicles rose. We were also astonished to discover that changes in the chemicals contained in the vesicles may be used to diagnose and predict renal function decrease.”
Extracellular vesicles are particles that are released by nearly all types of cells in our body and perform a variety of tasks. Because urinary extracellular vesicles (uEVs) include proteins from nephrons, they may be exploited as a source of biomarkers (molecules that indicate normal or aberrant processes) for a variety of disorders.
The researchers examined uEVs in urine samples from 26 children with healthy kidneys and 94 children with various kinds of CKD, including those born with smaller-than-average kidneys with fewer nephrons. The causes of CKD in children are less likely to be acquired factors and more likely to be structural abnormalities.
This made it easy for the researchers to identify and understand the alterations in uEVs that are linked to aberrant kidney anatomy.
“We employed nanoscale magnetic microbeads (made of iron oxide particles) coated with a chemical that attaches to EVs to collect extracellular vesicles in urine,” Harita added. “This approach allowed for the effective collection of uEVs even from renal disease patients who could only generate diluted urine. The size and quantity of protein present in the purified extracellular vesicles were measured. We discovered numerous distinct alterations in uEVs from children with CKD. Children with CKD, for example, have reduced amounts of a protein called MUC1 in their uEVs, which is critical for renal function.”