Test for Acute Renal Transplant Rejection

A study shows that a new diagnostic test employing measurements of cytotoxic genes in the RNA of urinary cells can predict those renal transplant patients who will develop acute rejection in about 80% of cases. The noninvasive test could substantially improve transplant treatment and outcome, say researchers from Weill Cornell Medical Center (New York, NY, USA), who developed the new genetic methodology. The study was published in the March 29 issue of The New England Journal of Medicine.

The researchers obtained urine samples from 22 renal-allograft recipients with a biopsy-confirmed episode of acute rejection and from 63 recipients with no evidence of rejection. They used a quantitative polymerase chain reaction (PCR) assay to measure messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B and a cyclophilin B gene, and correlated the level of expression with allograft status. Levels of perforin mRNA and granzyme B mRNA were higher in the urinary cells of the 22 patients with a confirmed rejection episode than in the patients with no evidence of rejection. They concluded that the test predicts acute rejection with a sensitivity and specificity of 83%.

The researchers then measured the levels of mRNA that encoded cytotoxic proteins in the urine samples of 37 transplant patients during the first nine days following transplantation and found the levels accurately identified those patients in whom acute rejection developed. Thus, the test could eliminate the need for repetitive needle biopsies. According to the researchers, the test may also have the potential to predict the development of acute rejection, while the methodology may lead to the molecular classification of rejection and to the development of therapeutic targets.