Forecast for exosomes
A urine test will help assess the risk of kidney rejection after transplantation
Kidney transplantation is always accompanied by a potential risk of rejection of the transplanted organ. Such a situation is not uncommon, it is observed in about 20% of cases, despite the therapy carried out in the postoperative period. The reason for transplant rejection is the reaction of the immune system, in which the recipient's immune cells recognize the transplanted organ as foreign.
Modern methods of diagnosing rejection of a transplanted kidney include a biopsy, which requires hospitalization and creates a risk of complications from the procedure. At the same time, about 70% of the results of morphological examination demonstrate the absence of pathology. Due to these limitations, researchers continue to look for alternative and simpler ways to assess the condition of the transplanted organ.
A study conducted in the USA suggests a new, non-invasive way to determine graft rejection. It is based on the determination of exosomes in a urine sample – tiny bubbles containing mRNA. The results of the work are presented in the Journal of the American Society of Nephrology (Fekih et al., Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection).
"Our goal is to develop better tools for monitoring patients without performing a biopsy. We try to detect rejection at an early stage in order to cure it before fibrosis appears," said one of the researchers, Dr. Jamil Azzi. "If rejection is not treated, it can lead to kidney failure."
The researchers obtained urine samples from 175 patients who had already had a kidney biopsy on the recommendation of doctors. Exosomes of cells were isolated from these samples. In turn, protein and mRNA were obtained from exosomes, which allowed us to obtain data on the signs of kidney rejection. The researchers identified a group of 15 genes, the activity of which can be judged on the violation of kidney function and their rejection. Additionally, five genes were identified that help distinguish between two types of rejection: cellular and antibody-mediated.
Based on the results obtained, Azzi and colleagues concluded that exosomes isolated from urine samples could be used as a marker of kidney transplant rejection. This work differs from previous attempts to characterize the role of mRNA in urine, since exosomes, rather than ordinary urine cells, were isolated. The shell of the exosome protects the mRNA from destruction. In a previous study, mRNA was isolated from cells that got into the urine from the kidneys. However, without extracellular vesicles, the genetic material was rapidly destroyed, which made it difficult to conduct this test in a clinical setting.
One of the limitations of the conducted study is that it involved patients who had previously had an assumption about the probable rejection of the transplant. In the future, Azzi and colleagues plan to apply the developed test on kidney transplant recipients with normal renal function to detect subclinical rejection.
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