Joseph Schwartz, PhD and Colleagues Identify Non-Invasive Method for Predicting Acute Cellular Rejection in Kidney Transplant Patients

November 11, 2013 - Kidney transplants save the lives of tens of thousands of people each year, but acute kidney rejection remains a major risk factor for losing the kidney after transplant. The current procedure for diagnosing acute rejection, which can be treated effectively with immunosuppressant drugs, requires a needle biopsy of the kidney. Dr. Schwartz and his colleagues used advanced statistical techniques to identify a genetic biomarker for acute rejection obtainable from urine specimens, potentially eliminating the need for invasive and expensive biopsies. The results of their study were published in the New England Journal of Medicine.

In a prospective study at five sites funded by the National Institutes of Health, the researchers compared histological data obtained from biopsy specimens with gene expression data obtained from concurrent urine specimens from the same patients. They identified a set of three messenger RNA molecules whose levels in urine predicted, with a high degree of sensitivity and specificity, which biopsy specimens would be diagnosed as acute cellular rejection.

By obtaining repeated urine specimens over the course of a year from patients in the study they were also able to demonstrate that the levels of the three-gene signature increased over time in patients who would later be diagnosed as suffering from acute cellular rejection while they remained flat in patients with normal biopsies and clinically stable graft function. 

The availability of a direct non-invasive measure for predicting acute cellular rejection in kidney grafts presents researchers and clinicians with an opportunity to adjust levels of immunosuppressant therapy before clinical signs of rejection appear, potentially staving off rejection.

The article, titled “Urinary-Cell mRNA Profile and Acute Cellular Rejection in Kidney Allografts,” was published in the July 4, 2013 edition of the New England Journal of Medicine.