A Urine Test for Acute Kidney Rejection?

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A new test based on a “three-gene signature” can detect acute rejection of kidney allografts well before diagnosis by biopsy, according to a report in the New England Journal of Medicine.

In prospective, blinded fashion, the researchers developed the test using 4300 urine samples from 485 kidney allograft recipients, collected from 3 days through 12 months after transplantation. The goal was to identify messenger RNA (mRNA) levels in urinary cells that were correlated with the presence of acute graft rejection.

Normalized for 18S ribosomal RNA (rRNA) level, the combination of CD3ε mRNA, IFN-inducible protein 10 (IP-10) mRNA, and 18S rRNA provided a three-gene signature capable of differentiating between the presence and absence of rejection on allograft biopsy specimens. On receiver operating characteristic curve analysis, the area under the curve was 0.85 in the development set and 0.74 in an independent validation set.

The three-gene signature distinguished acute cellular rejection from acute antibody-mediated and borderline rejection. It also permitted diagnosis of acute cellular rejection in patients receiving anti–IL-2 antibodies versus T cell–depleting antibodies. Test performance was unaffected by the presence of urinary tract infection.

The average trajectory of the three-gene signature increased significantly in the weeks before the diagnosis of acute rejection could be made in biopsy specimens. By contrast, in patients without rejection, the level remained below the diagnostic threshold.

A molecular signature consisting of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels detected in urinary cells provides a promising, noninvasive test for acute rejection after kidney allograft transplantation. The three-gene signature “may provide a direct measure of risk…and a means of assessing immune status with repeated assessments,” the investigators said. With further evaluation, the test could be useful in the earlier identification of acute rejection, permitting individualized immunosuppressive therapy [Suthanthiran M, et al. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med 2013; 369:20–31].