Researchers are pursuing a new approach to screening and identifying patients who may have renal failure.
A team, led by Rania El Fekih, MD, Renal Department, Transplantation Research Center, Brigham and Women’s Hospital and Children’s Hospital, Harvard Medical School, used urine samples with matched biopsy samples to detect urinary exosomal mRNAs and developed names- written rejection on the basis of a different gene expression.
Traditional Biomarkers
The conventional biomarkers used to monitor a renal allograft for rejection are often the late signs of injury and lack the required sensitivity and specificity. However, invasive, but costly, allograft biopsies indicate the need for a noninvasive clinical trial that can properly diagnose renal allograft rejection to improve allograft results.
In the urinary exosome, tiny vesicles are released into the urine that carry parent cell proteins and nucleic acid, reflecting the biological function of the parent cells within the kidney, causing its -integration of immune cells. Urine is stable enough to make them a useful tool for liquid biopsies and a noninvasive diagnostic biomarker for renal transplant rejection.
The researchers used 192 of 220 urine samples with identical biopsy samples from 175 patients who underwent clinically identified renal transplant biopsy.
To assess the performance of the signatures on multiple subsets of data, the auditors used cross-validation.
Results
The researchers found that exosomal mRNA signature distinguished biopsy samples from patients with all-cause rejection and those without rejection. This resulted in an under-loop range (AUC) of 0.93 (95% CI, 0.87–0.98), which was significantly better than the standard of care (increase in AUC eGFR, 0.57; 95% CI, 0.49–0.65 ).
Moreover, the negative predictive value of the exosome-based signature was 93.3% and the positive prediction value was 86.2%.
While using the same approach, the researchers identified an additional gene signature that discriminated patients with T-cell mediated rejection from those with median rejection (with an AUC of 0.87 ; 95% CI, 0.76-0.97), with a negative prediction value. of 90.6% and a positive forecast value of 77.8%.
“Our findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool for screening for renal allograft rejection,” the authors wrote. “This discovery has the potential to help clinicians make therapeutic decisions. ”
Need for improvement
Despite effort and recognition, new research shows that renal transplantation has not improved significantly in the last 2 decades for patients with end-stage renal failure (EKSD).
In recent decades researchers have studied and promoted many policies to improve access to renal transplants for patients with end-stage renal disease. However, there is still a wide variation in transmission rates between different dialysis facilities.
The study included 1.3 million adult patients in whom the four-year cumulative WLT accounted for 29.7%. This had not changed over 5 periods. The preemptive WLT before dialysis increased by age from 5.2% in 1997-2000 to 9.8% in 2013-2016.
The study, “Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection,” was published online in the Journal of the American Nephrology Society.