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For patients who need a kidney transplant, the waiting time can take up to six years.
Even if they receive a transplant, up to 20% of patients will experience rejection.
Transplant rejection occurs when the recipient's immune cells recognize the newly received kidney as a foreign body and refuse to accept the donor's antigen.
Current methods of testing for renal rejection include invasive biopsy procedures, which result in patients requiring hospitalization for several days.
A study conducted by researchers at Brigham and Women’s Hospital and Exosome Diagnostics proposes a new non-invasive method that uses exosomes (microvesicles containing mRNA) in urine to test for transplant rejection.
Their findings were published in the Journal of the American Society of Nephrology.
"Our goal is to develop better tools to monitor patients without the need for unnecessary biopsies.
We try to detect rejection as early as possible so that it can be treated before scars form," said Jamil, associate physician at the Brigham Kidney Transplant Department.
Azzi said: "If rejection is not treated, it can lead to scarring and complete kidney failure.
Because of these problems, recipients may face lifelong side effects.
Before this study, when doctors suspected that the transplant recipient had rejected the donor organ, they ordered a biopsy or blood test.
The biopsy procedure carries a risk of complications, and 70-80% of biopsy results are normal.
In addition, blood tests for creatinine do not always give definitive results.
Due to the limitations of current tests, researchers are looking for alternative and simpler methods to evaluate the effect of transplantation.
In this study, researchers collected urine samples from 175 patients who had undergone a kidney biopsy recommended by a doctor.
From these samples, the researchers isolated urine exosomes from the immune cells of the newly transplanted kidney.
The researchers isolated proteins and mRNA from these vesicles, and determined the rejection signal (a set of 15 genes), which can distinguish whether rejection has occurred.
It is worth noting that the researchers also identified five genes that can distinguish two types of rejection: cellular rejection and antibody-mediated rejection.
"These findings suggest that exosomes isolated from urine samples may be viable biomarkers of kidney transplant rejection," Azzi said.
This study is different from previous attempts to characterize urine mRNA because clinicians isolated exosomes instead of ordinary urine cells.
Exosomal vesicles can protect mRNA from degradation, so that it is possible to check whether genes in mRNA have matching rejection characteristics.
In previous studies, mRNA was isolated from cells shed into the urine from the kidneys.
However, if there are no extracellular vesicles to protect the mRNA, the mRNA will be quickly degraded, which makes the test difficult to perform in a clinical setting.
Azzi said: "Our research shows that if urine is obtained from patients at different time points and mRNA is measured from microvesicles, it shows that it will not disappear over time, so that it can accurately assess whether the transplant has been rejected.
Information source: Novel urine test developed to diagnose human kidney transplant rejection
Original source: Rania El Fekih et al, Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection, Journal of the American Society of Nephrology (2021).