Test could possibly replace invasive biopsies to help guide treatment

A new noninvasive urine test can distinguish among different causes of acute kidney dysfunction after transplantation. The test, which is described in a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN), may allow patients to avoid invasive kidney biopsies when their transplanted organ is not functioning properly.

When creatinine levels are elevated in the blood of a kidney transplant recipient, it is an indication that the transplanted kidney is not functioning well. There are several reasons for transplant kidney dysfunction, and none of the blood or urine tests can reliably differentiate them. Because it is important to establish the exact reason for kidney dysfunction in order to determine the appropriate treatment, physicians typically perform a needle biopsy of the transplanted kidney.

Now, however, Thangamani Muthukumar, MD (Weill Medical College of Cornell University) and his colleagues have developed a urine test that measures the levels of several messenger RNAs (mRNAs) that are directly related to the disease processes that cause kidney dysfunction. The researchers measured absolute levels of mRNAs in 84 urine samples from 84 kidney transplant recipients who had undergone needle biopsy of the transplanted kidney to determine the cause of their acute kidney dysfunction.

“Using statistical methods we have combined the mRNAs to yield a diagnostic signature,” explained Dr. Muthukumar. The researchers developed two such signatures from cells found in the urine that could differentiate, in a two-step approach, the common causes of acute kidney dysfunction with high accuracy.

“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,” said Dr. Muthukumar.

The first author of the study is Dr. Marie Matignon, MD. Study co-authors include Ruchuang Ding, MD, Darshana M. Dadhania, MD, Franco B. Mueller, MD, Choli Hartono, MD, Catherine Snopkowski, Carol Li, John R. Lee, MD, Daniel Sjoberg MA, Surya V. Seshan, MD, Vijay K. Sharma, PhD, Hua Yang, MD, Bakr Nour, MD, Andrew J. Vickers, PhD, and Manikkam Suthanthiran, MD.

Disclosures: The authors reported no financial disclosures.

This work was supported, in part, by an award from the Assistance Publique-Hôpitaux de Paris and Institut Fédératif de Recherche en Néphrologie et Transplantation (IFRNT), France (to Marie Matignon), Qatar National Research Foundation Award NPRP 08-503-3-111 (to Bakr Nour and Manikkam Suthanthiran), National Institutes of Health Grants 2R37-AI051652 (to Manikkam Suthanthiran) and K08-DK087824 (to Thangamani Muthukumar), and Weill Cornell Medical College Clinical and Translational Science Center Award UL1TR000457.