Kidney Transplant Outcomes Predicted by Urine Test

Levels of a certain protein in the urine of kidney transplant patients can distinguish between those at high risk of kidney injury from those at low risk, according to an organ transplantation study.

In the multicenter Clinical Trials in Organ Transplantation study, doctors periodically collected urine samples from 280 adult and child kidney transplant recipients for two years after transplantation. Investigators led by Peter Heeger, MD, of the Icahn School of Medicine at Mount Sinai (New York, NY, USA) and Donald Hricik, MD, of Case Western Reserve University (Cleveland, OH, USA) measured the urinary levels of molecules that had previously been associated with rejection. These included two proteins and nine messenger RNAs (mRNAs). They identified CXCL9 protein and CXCL9 mRNA as potential biomarkers for the prediction of rejection.

Low levels of the protein biomarker also could identify patients likely to have stable long-term kidney function. Transplant recipients with low urinary CXCL9 protein six months after transplantation were unlikely to experience rejection or loss of kidney function over the next 18 months. In addition, detection of the protein in the urine of transplant recipients was more straightforward than measuring mRNA levels. While proteins can be measured directly in urine, mRNAs must first be extracted from urine samples.

The results of the study also suggest that low levels of the protein CXCL9, can rule out rejection as a cause of kidney injury.

Kidney transplant recipients have to take immunosuppressive drugs every day to prevent rejection. But these drugs themselves can cause kidney damage and lead to other serious side effects such as cancer, infection, and infertility. Even with immunosuppressive therapy, 10% to 15 % of kidney recipients experience rejection during the first year after transplantation.

Today, the only definitive way to distinguish rejection from other causes of kidney injury is by performing a kidney biopsy to look for rejection-associated damage. This procedure is generally considered safe but it carries some minor risks for the patient and does not always provide an accurate impression of the overall state of the kidney.

"A noninvasive urine test to accurately monitor the risk of kidney rejection could dramatically reduce the need for biopsies and possibly enable doctors to safely reduce immunosuppressive therapy in some patients," said NIAID director Anthony S. Fauci, MD. "The results of this study support the further development of noninvasive tests for the detection and management of transplant rejection."

The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD, USA), part of the US National Institutes of Health. It appears online in the August 22, 2013, American Journal of Transplantation.

Related Links:
Icahn School of Medicine at Mount Sinai
Case Western Reserve University
National Institute of Allergy and Infectious Diseases