Levels of a protein in the urine of kidney transplant recipients can distinguish those at low risk of developing kidney injury from those at high risk, a study suggests.
The results also suggest that low levels of this protein, called CXCL9, can rule out rejection as a cause of kidney injury. The multicenter study appeared online Aug. 22 in the American Journal of Transplantation.
To prevent rejection, kidney transplant recipients typically take immunosuppressive drugs daily. However, these drugs 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.
The only definitive way to distinguish rejection from other causes of kidney injury is by performing a biopsy, in which physicians remove a small piece of kidney tissue to look for rejection-associated damage. Although this procedure generally is considered safe, it presents minor risks for patients and does not always provide an accurate impression of the kidneys overall condition.
“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,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which funded the study, said in a news release. “The results of this study support the further development of noninvasive tests for the detection and management of transplant rejection.”
In the study, physicians 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 in New York City, and Donald Hricik, MD, of Case Western Reserve University in Cleveland, measured the urinary levels of molecules previously associated with rejection. These included two proteins and nine messenger RNAs — intermediary molecules in the construction of proteins from genes. They identified CXCL9 protein and CXCL9 mRNA as potential biomarkers for the diagnosis of rejection.
After further testing, the researchers found CXCL9 protein was better at ruling out rejection than any of the mRNAs tested. Low levels of the protein biomarker also could identify patients likely to have stable long-term kidney function, according to their findings. Transplant recipients with low urinary CXCL9 protein six months after transplantation were unlikely to experience rejection or loss of kidney function during the next 18 months.
Detection of the protein also was more straightforward than measuring mRNA levels. Proteins can be measured directly in urine, but mRNAs first must be extracted from urine samples, which is challenging. The researchers obtained sufficient mRNA from only 76% of samples.
CXCL9 protein levels also may be useful for predicting and monitoring transplant rejection. The investigators discovered urinary CXCL9 levels began to increase as many as 30 days before clinical signs of kidney injury, which could give physicians a chance to intervene. The protein levels began to drop after treatment for rejection, suggesting the urine test also could be used to monitor treatment progress.
Study abstract: http://onlinelibrary.wiley.com/doi/10.1111/ajt.12426/abstract.