Chronic kidney disease, also known as chronic renal disease or CKD, is a condition characterized by a gradual loss of kidney function over time. Children with chronic kidney failure may not have any symptoms until about 80% of their kidney function is lost. Now researchers at the University of Tokyo report a novel approach analyzing urine extracellular vesicles (uEVs) in urine samples identifies changes in the kidneys earlier than conventional methods and can also predict renal function decline. The researchers studied urine samples from children with and without CKD. Their findings revealed the size and content of uEVs change with decreasing kidney function. This proof of concept may help with developing new tests that can help detect the disease earlier and may lead to the development of similar tests for other diseases.

The new study, “Urinary extracellular vesicles signature for diagnosis of kidney disease,” is published in iScience.

“Congenital disorders characterized by the quantitative and qualitative reduction in the number of functional nephrons are the primary cause of CKD in children,” wrote the researchers. “We aimed to describe the alteration of uEVs associated with decreased renal function during childhood. By nanoparticle tracking analysis and quantitative proteomics, we identified differentially expressed proteins in uEVs in bilateral renal hypoplasia, which is characterized by a congenitally reduced number of nephrons.”

“We found that changes in tiny structures called extracellular vesicles in urine are valuable in the diagnosis of kidney disease,” explained associate professor Yutaka Harita from the Graduate School of Medicine. “The percentage of larger vesicles increased with decreased kidney function. We were also surprised to learn that we can use changes in the molecules contained in the vesicles to diagnose and predict renal function decline.”

The team looked at uEVs in urine samples from 26 children with healthy kidneys and 94 children who have various types of CKD. In children, the causes of CKD are less likely to be due to acquired factors and more likely to be due to structural abnormalities. This made it easier for the researchers to identify the changes in uEVs.

“To collect extracellular vesicles in urine, we used nanoscale magnetic microbeads (made up of iron oxide particles) coated with a molecule that binds to EVs,” explained Harita. “This method enabled efficient collection of uEVs even from patients with kidney disease who could only produce diluted urine. The size of the purified extracellular vesicles and the amount of protein contained in them were analyzed. We found several unique changes in uEVs from children with CKD. For example, children with CKD had lower levels of a protein called MUC1, important for kidney function, in their uEVs.”

These findings pave a path towards using uEVs for early identification of CKD and to complement existing methods.

“We want to conduct studies on a larger scale to establish a new urine test using extracellular vesicles. We would also like to examine the utility of combining the new methods with existing tests for various diseases and age groups,” concluded Harita.