Urine test can diagnose, predict kidney transplant rejection

NIH-funded study describes noninvasive alternative to kidney biopsy

2013-07-04

(Press-News.org) Analysis of three biomarkers in the urine of kidney transplant recipients can diagnose -- and even predict -- transplant rejection, according to results from a clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. This test for biomarkers -- molecules that indicate the effect or progress of a disease -- offers an accurate, noninvasive alternative to the standard kidney biopsy, in which doctors remove a small piece of kidney tissue to look for rejection-associated damage. The findings appear in the July 4 issue of the New England Journal of Medicine.

"The development of a noninvasive test to monitor kidney transplant rejection status is an important advance that will allow doctors to intervene early to prevent rejection and the kidney injury it causes, which should improve long-term outcomes for transplant recipients," said NIAID Director Anthony S. Fauci, M.D.

Following a kidney transplant, patients receive therapy to prevent their immune systems from rejecting the organ. Even with this immunosuppressive therapy, approximately 10 to 15 percent of kidney recipients experience rejection within one year after transplantation.

Typically, a biopsy is performed only after a transplant recipient shows signs of kidney injury. Although the procedure seldom causes serious complications, it carries some risks, such as bleeding and pain. In addition, biopsy samples sometimes do not give doctors an accurate impression of the overall state of the kidney because the samples are small and may not contain any injured tissue.

"Potentially, a noninvasive test for rejection would allow physicians to more accurately and routinely monitor kidney transplant recipients," said Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology and Transplantation. "By tracking a transplant recipient's rejection status over time, doctors may be able to modulate doses of immunosuppressive drugs to extend the survival of the transplanted kidney." In the study, part of the NIH-funded Clinical Trials in Organ Transplantation (CTOT), investigators at five clinical sites collected urine samples from 485 kidney transplant recipients from three days to approximately one year after transplantation. Researchers led by Manikkam Suthanthiran, M.D., of Weill Cornell Medical College in New York and Abraham Shaked, M.D., Ph.D., of the University of Pennsylvania School of Medicine, Philadelphia, assessed the urinary cell levels of several biomarkers that previously have been associated with rejection.

Statistical analysis revealed that a group of three urinary biomarkers formed a diagnostic signature that could distinguish kidney recipients with biopsy-confirmed rejection from those whose biopsies did not show signs of rejection or who did not undergo a biopsy. The biomarkers include two messenger RNA molecules that encode immune system proteins implicated in transplant rejection and one noncoding RNA molecule that participates in protein production. The researchers used the signature to assign values to each urine sample and identify a threshold value indicative of rejection. With this test, they could detect transplant rejection with a high level of accuracy. The investigators obtained similar results when they tested a set of urine samples collected in a separate CTOT clinical trial, thereby validating the diagnostic signature.

To determine whether the urine test also could predict future rejection, the scientists analyzed trends in the diagnostic signature in urine samples taken in the weeks before an episode of rejection. The values for patients who experienced rejection increased slowly but steadily leading up to the event, with a characteristic sharp rise occurring approximately 20 days before biopsy confirmed rejection had occurred. In contrast, the values for patients who did not show any clinical signs of rejection remained relatively constant and under the threshold for rejection. These findings suggest that it might be possible to treat impending rejection before substantial kidney damage occurs.

"The test described in this study may lead to better, more personalized care for kidney transplant recipients by reducing the need for biopsies and enabling physicians to tailor immunosuppressive therapy to individual patients," said NIAID Transplantation Branch Chief Nancy Bridges, M.D., a co-author of the paper. The CTOT cooperative research consortium provided the infrastructure and collaborative environment needed to conduct the large, rigorous, multicenter study that established the efficacy of this biomarker-based test, Dr. Bridges noted.

###

This work was funded by NIAID, NIH, under grant numbers U01AI63589 and R37AI051652, and the National Center for Advancing Translational Sciences, NIH, under grant number UL1RR024996. The Qatar National Research Fund also provided financial support. The ClinicalTrials.gov identifier for the study Urine Testing to Detect Kidney Transplant Rejection is NCT00337220.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH...Turning Discovery Into Health®

Reference:

M Suthanthiran et al. Urinary cell mRNA profile and acute cellular rejection in kidney allografts. New England Journal of Medicine DOI: 10.1056/NEJMoa1215555 (2013).

ELSE PRESS RELEASES FROM THIS DATE:

Violent video games don't always reduce subsequent helpfulness

2013-07-04

Violent or antisocial video games like Call of Duty or Grand Theft Auto do not reliably reduce helpful behaviors in players shortly after playing, according to research published July 3 in the open access journal PLOS ONE by Morgan Tear and Mark Nielsen from the University of Queensland, Australia. Participants in the research played one of four video games for 20 minutes. At the end of the test, a researcher pretended to drop some pens and assessed how many players helped pick them up. Regardless of the game played, only about 40-60% of participants helped pick up pens ...

Tweet timing tells bots, people and companies apart

2013-07-04

Tweet timing can differentiate individual, corporate and bot-controlled Twitter accounts independent of the language or content of a tweet, according to research published July 3 in the open access journal PLOS ONE by Aldo Faisal and Gabriela Tavares from Imperial College London, UK. The researchers studied over 160,000 tweets from personal accounts held by individuals, 'managed' accounts belonging to large, well-known corporations and 'bot-controlled' accounts chosen from online lists of Twitter bots. Periods of high or low Twitter activity and the time between successive ...

Genetic factors shaping salamander tails determine regeneration pace

2013-07-04

Salamanders' capacity to regrow lost limbs may seem infinite when compared with that of humans, but even amongst salamanders, some species regenerate body parts very slowly, while others lose this capacity as they age. Now, researchers have found that salamanders' capacity to regrow a cut tail depends on several small regions of DNA in their genome that impact how wide the tail grows. The results are published July 3 in the open access journal PLOS ONE by Randal Voss and colleagues from the University of Kentucky. In the study, approximately 66-68% of the differences ...

Biomarker predicts heart attack risk based on response to aspirin therapy

2013-07-04

DURHAM, N.C. -- Aspirin has been widely used for more than 50 years as a common, inexpensive blood thinner for patients with heart disease and stroke, but doctors have little understanding of how it works and why some people benefit and others don't. Now researchers at Duke Medicine have solved some of the mysteries related to the use of this century-old drug, and developed a blood-based test of gene activity that has been shown to accurately identify who will respond to the therapy. The new gene expression profile not only measures the effectiveness of aspirin, but ...

Archaeologists unearth carved head of Roman god in ancient rubbish dump

2013-07-04

An 1,800-year-old carved stone head of what is believed to be a Roman god has been unearthed in an ancient rubbish dump. Archaeologists made the discovery at Binchester Roman Fort, near Bishop Auckland in County Durham, England. First year Durham University archaeology student Alex Kirton found the artefact, which measures about 20cm by 10cm, in buried late Roman rubbish within what was probably a bath house. The sandstone head, which dates from the 2nd or 3rd century AD, has been likened to the Celtic deity Antenociticus, thought to have been worshipped as a source ...

Clues about autism may come from the gut

2013-07-04

Bacterial flora inhabiting the human gut have become one of the hottest topics in biological research. Implicated in a range of important activities including digestion, fine-tuning body weight, regulating immune response, and producing neurotransmitters affect that brain and behavior, these tiny workers form diverse communities. Hundreds of species inhabit the gut, and although most are beneficial, some can be very dangerous. In new research appearing in the journal PLOS ONE, a team led by Rosa Krajmalnik-Brown, a researcher at Arizona State University's Biodesign Institute, ...

Homicide by mentally ill falls, but patient suicide rises in England

2013-07-04

The number of people killed by mental health patients has fallen to its lowest level in a decade -- figures released today show. Experts suggest the fall in homicide reflects safer patient care and point to the possible effect of better treatment of drug and alcohol problems as well as new legal powers in the community. But suicides among mental health patients increased with the current economic difficulties a likely factor. The findings, reported in the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI) produced by The ...

Improved outlook for immune-based therapies

2013-07-04

The idea of fighting infections and even cancers by inducing protective immune responses may now be a step closer to clinical practice. Researchers have removed a major obstacle to widespread use of so-called adoptive transfer therapy, in which a patient receives "killer" immune cells targeting a disease agent. Existing technologies can easily provide T cells that will recognize a specific antigen, but it has been challenging to identify individual cells most likely to succeed in fighting the disease – until now. Scientists at the Technische Universitaet Muenchen (TUM) ...

Genetic signals reflect the evolutionary impact of cholera

2013-07-04

An international research team has used a novel approach to identify genetic factors that appear to influence susceptibility to cholera. The findings by investigators from Massachusetts General Hospital (MGH), the Broad Institute and the International Center for Diarrhœal Disease Research, Bangladesh (ICDDR,B) indicate the importance of pathways involved in regulating water loss in intestinal cells and of the innate immune system in the body's response to the bacteria that causes cholera, which affects from 3 to 5 million people each year and causes more than 100,000 deaths. ...

First comprehensive regulatory map is a blueprint for how to defeat tuberculosis

2013-07-04

Despite decades of research on the bacterium that causes tuberculosis (TB), scientists have not had a comprehensive understanding of how the bacterium is wired to adapt to changing conditions in the host. Now, researchers at Stanford University, Seattle BioMed, Boston University and the Broad Institute, Max Planck Institute of Biology in Berlin, Germany, Caprion Proteomics Inc. in Montreal, Canada, Brigham and Woman's Hospital (Harvard University), and Colorado State University have taken the first steps toward a complete representation of the regulatory network for Mycobacterium ...

Urine test can diagnose, predict kidney transplant rejection

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: