Urinary RNA Assay May Replace Needle Biopsy for Detection of Kidney Transplant Rejection

Determination of mRNA signatures in urine samples may replace needle biopsy for diagnosing kidney dysfunction following transplant surgery.

Investigators at Weill Cornell Medical College (New York, NY, USA) measured absolute levels of 26 pre-specified mRNAs in urine samples collected from kidney graft recipients at the time of needle biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction would be feasible using urinary cell mRNA profiles. They profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell–mediated rejections and 26 acute antibody-mediated rejections) and 32 urine samples from 32 patients with acute tubular injury without acute rejection.

Results of stepwise discriminant mRNA analysis identified a linear combination of mRNAs for CD3epsilon, CD105, TLR4, CD14, complement factor B, and vimentin that distinguished acute rejection from acute tubular injury. Among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3epsilon, CD105, CD14, CD46, and 18S rRNA that distinguished T cell–mediated rejection from antibody-mediated rejection.

“Using statistical methods we have combined the mRNAs to yield a diagnostic signature,” said senior author Dr. Thangamani Muthukumar, assistant professor of medicine at Weill Cornell Medical College. “Our study shows that when the creatinine level is elevated in the blood of a kidney transplant recipient, use of our urine test would differentiate the common causes of kidney dysfunction that led to the elevation in creatinine, hence benefiting many patients by allowing them to avoid the need for an invasive needle biopsy.”

The study showing the correspondence between mRNA signatures and needle biopsy results was published in the March 7, 2014, online edition of the Journal of the American Society of Nephrology.

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