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Study Expands Use of Biomarker for Early Diagnosis of Acute Kidney Injury

A biomarker test developed initially to identify early acute kidney injury (AKI) after surgery has been shown to successfully detect AKI in emergency room patients with a variety of urgent health issues.

In a study published online Sept. 5 in the Clinical Journal of the American Society of Nephrology, the findings expand the overall utility and potential medical settings for using the test, according to researchers.

The test measures the protein neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of early AKI. It was invented by researchers at Cincinnati Children’s Hospital Medical Center to detect AKI earlier than existing methods, and to more promptly begin treatment.

“The majority of our studies on NGAL have been performed in well controlled settings of hospital-acquired AKI, such as cardiac surgery, contrast administration or other critically ill patients,” said Prasad Devarajan, MD, senior author and director of Nephrology and Hypertension at Cincinnati Children’s. “The purpose of this study was to determine the biomarker’s accuracy in a diverse group of patients admitted from the emergency department, where patients with early signs of AKI are often misdiagnosed.”

The study involved patients admitted through the emergency room of Fernando Fonseca Hospital in Portugal, which also closely collaborated on the study. The findings demonstrate the NGAL test, which uses a single drop of blood and provides results within 15 minutes, was able to accurately distinguish AKI from reversible transient kidney dysfunction.

Of 616 patients who participated in the study, individuals who were subsequently diagnosed with true AKI had the highest levels of NGAL detected at the time of hospital admission. The study also identified a cutoff point in NGAL levels above which the risk of acute kidney injury increases tenfold.

Results of a study previously published in 2008 by Devarajan showed that the NGAL test predicted AKI in pediatric heart surgery patients within hours instead of days, allowing treatment that prevented serious damage to kidneys. Prior to the NGAL test, serum creatinine was the only reliable method for detecting kidney damage; however, the long wait for results often resulted in permanent kidney damage.

With a growing number of patients coming to emergency rooms with community-acquired AKI, Devarajan says having a rapid, reliable method of detecting kidney injury is increasingly important.

“This latest study showed that this simple laboratory test provides an accurate prediction of acute kidney injury and its severity in a diverse clinical setting,” said Devarajan. “The identification of biomarkers that differentiate intrinsic AKI from transient reversible forms of renal dysfunction and predict outcomes is a high priority.”

Study: Plasma NGAL for the Diagnosis of AKI in Patients Admitted from the Emergency Department Setting [Clinical Journal of the American Society of Nephrology]

Source: EurekAlert!

BIDMC Cardiovascular Institute Researchers Will Lead $4 Million NIH Grant to Study MicroRNAs

A cardiovascular research team from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH), led by BIDMC Principal Investigator Saumya Das, MD, PhD, has been awarded a $4 million Common Fund grant from the National Institutes of Health (NIH) as part of a newly formed program on Extracellular RNA Communication. The five-year grant will focus on identifying microRNA biomarkers in heart disease.

Each year, complications from heart attacks (myocardial infarctions) contribute to more than half a million cases of heart failure and 300,000 cases of sudden cardiac arrest, when the heart suddenly stops. Both of these conditions are closely related to a process known as remodeling, in which the structure and function of the heart changes – or remodels — following a heart attack.

“Our goal is to explore the role that microRNAs play in predicting which heart-attack patients will go on to experience complications,” explains Das, an electrophysiologist in BIDMC’s Cardiovascular Institute and co-director of the cardiovascular genetics program within the Outpatient Cardiovascular Clinic.

“Current strategies used to identify the highest risk patients have often been inaccurate,” he adds. “We think that a blood test that makes use of microRNA biomarkers could replace existing strategies and more accurately predict which patients might experience poor outcomes and thereby identify who would most benefit from frequent monitoring and medical care.” Other investigators who are part of the NIH grant, “Plasma miRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction,” include BIDMC Director of Cardiovascular Research Anthony Rosenzweig, MD, and BWH investigators Raymond Y. Kwong, MD, MPH, and Mark Sabatine, MD, MPH.

microRNAs are one type of extracellular RNA. Once considered nothing more than genomic “junk,” microRNAs have more recently been recognized as playing a key role in cellular functions. Several years ago, scientists began to recognize that these small, noncoding RNAs were not only found inside cells, but could also be found in blood and other tissue fluids.

Using patient plasma samples from extensively characterized patients who have suffered heart attacks, the scientific team will first identify which specific microRNAs are related to poor heart remodeling. They will then use cell culture and animal models of heart disease to further prioritize which microRNAs play a functional role in disease progression. Finally, the investigators will validate these prioritized microRNAs as prognostic markers for poor health outcomes after heart attacks in a large prospective clinical trial.

“Ultimately, we think that miRNA-based tests could replace current tests to predict which patients might be at risk of complications and, therefore, be good candidates to receive an implanted defibrillator,” says Das. “At the same time, we hope to be able to better predict which individuals are at less risk of complications – and thereby spare them unnecessary and costly procedures.”

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide.

BIDMC has a network of community partners that includes Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Health Care, Commonwealth Hematology-Oncology, Beth Israel Deaconess HealthCare, Community Care Alliance, and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Senior Life and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Source: Beth Israel Deaconess Medical Center

New Data Suggests Abbott’s High Sensitive Troponin Test May Help Doctors More Accurately Diagnose Heart Attacks in Women

Abbott recently announced promising preliminary results from a study presented at the ESC Congress 2013, suggesting that its high sensitive troponin test may help doctors improve the diagnosis and prognosis of patients presenting with symptoms of a heart attack. The test could be particularly beneficial for women, who may have different presenting symptoms and are often under-diagnosed. The study, which is being conducted by researchers at the University of Edinburgh, is evaluating Abbott’s ARCHITECT STAT High Sensitive Troponin-I (hsTnI) test, which received CE Mark in January 2013.

Cardiac troponin, a protein found in the heart muscle, is considered the preferred biomarker to identify suspected heart attacks, because it can detect injury to the heart.3 Abbott’s hsTnI test can measure very low levels of this protein, which is especially important for women, who often have lower levels of troponin than men.4

Researchers shared data from the first 1,126 patients of the study presenting with symptoms of a heart attack. Early findings demonstrate that women have lower peak levels of troponin than men, contributing to the under-diagnosis and therefore under-treatment of heart attacks for women.

“Whilst men and women are just as likely to present to the emergency department with chest pain, currently men are twice as likely to be diagnosed with a heart attack. By using the Abbott high sensitive troponin test and different diagnostic thresholds for men and women, the frequency of diagnosis of heart attacks in women increased and was comparable to men,” said Dr. Nicholas Mills, one of the key study authors and cardiologist, University of Edinburgh. “The findings of our study, when completed, could change the way we diagnose heart attacks in women, potentially reducing inequalities in the treatment and outcomes, and enabling everyone to receive the best care.”

When completed in 2016, this study will include more than 25,000 patients across 10 centers in Scotland, making it one of the largest studies to evaluate the impact of high sensitive troponin tests on patient care. The study was funded by a special project grant from the British Heart Foundation with Abbott providing the ARCHITECT STAT hsTnI assay.

“While Abbott’s high sensitive troponin test benefits both men and women with earlier detection of heart attacks, the potential to increase the diagnosis among women is especially important,” said John Frels, PhD, divisional vice president, Diagnostics Research, Abbott. “This is the first time we have seen a test that can provide this kind of detailed information to doctors and has the potential to aid doctors with improving the odds of survival for women with heart attacks.”

The ARCHITECT STAT hsTnI assay is commercially available in several countries in Europe, as well as Canada, Australia, New Zealand, and Brazil and runs on Abbott’s fully automated ARCHITECT family of analyzers. The test is currently for research-use only in the United States.

Source: Abbott Diagnostics

Researchers Develop Rapid, Cost-effective Early Detection Method for Organ Transplant Injury

A recently reported blood test for the early detection of organ transplant injury could enable more timely therapeutic intervention in transplant patients and thus help to avoid longer term damage. As described by scientists at the University Medical Center Göttingen and Chronix Biomedical, a molecular diagnostics company, the new method uses Bio-Rad Laboratories’ Droplet Digital PCR (ddPCR™) technology to overcome the obstacles of earlier tests, which were both time-consuming and costly. The method was presented at the American Association of Clinical Chemistry (AACC) 2013 annual meeting and has been accepted for publication in Clinical Chemistry.

Approximately 28,000 organ transplantations (known as grafts) are performed each year in the U.S., with another 100,000 patients on waiting lists. However, transplant patients are often subject to organ rejection: acute rejection of liver transplants within three years is nearly 22 percent, while heart and lung rejection is close to 50 percent. In addition, nearly half of all of kidney transplants fail within 10 years.

Graft-derived cell-free DNA (GcfDNA) in the circulation of transplant recipients is a potential rejection biomarker. But previous attempts to determine GcfDNA, which require parallel sequencing of donor and recipient DNA, are expensive and require a long turnaround and use of donor DNA. University Medical Center Göttingen and Chronix Biomedical researchers sought to develop a new method in an attempt to address these drawbacks.

Using ddPCR for Fast, Cost-Effective Test

The researchers applied Bio-Rad’s ddPCR technology to quantify graft-derived cfDNA in recent liver transplant patients and in stable patients who had undergone a transplant procedure more than six months earlier. ddPCR technology allowed them to develop a cost-effective and fast laboratory test that detects cfDNA being released into the blood stream by dying cells from the transplanted organ.

“GcfDNA from dying graft cells are the most direct and sensitive indicator of organ rejection and we needed an instrument that could measure it,” said Chronix Biomedical’s Chief Technology Officer and the study’s senior author, Ekkehard Schuetz, MD, PhD. “ddPCR added an additional level of reliability and precision to traditional PCR.”

Sequencing methods typically require batch sampling, but by using ddPCR, researchers are able to run single samples. Additionally, this method is reducing test time from three days or more to one day and costs by 90 percent. The study authors were able to address the need for donor DNA by preselecting SNPs that ensure enough heterogeneity between donor and recipient. The new blood test can also deliver results up to several days before the conventional aspartate aminotransferase (AST) and bilirubin tests for liver transplantation rejection, with the potential for an immediate positive impact on patient care.

“We will now be able to detect subclinical rejection and early intervention may allow us to avoid a full-blown rejection,” said Michael Oellerich, M.D., FACB, FRCPath and Lower Saxony Distinguished Professor of Clinical Chemistry at the University Medical Center Göttingen and study Principal Investigator. “This test may be useful to personalize immunosuppression and to improve long-term outcomes.”

“Detecting non-host cfDNA is the third example for the commercial potential of cfDNA diagnostics. Researchers will now be able to extend the applications from fetal cfDNA in maternal blood and personalized biomarkers for minimal residual disease in cancer to solid organ transplantation,” said Howard Urnovitz, PhD, Chronix Biomedical’s Chief Executive Officer.

“We are looking forward to the improvements in precision medicine we can offer with ddPCR and this example in transplantation highlights the diagnostic value for the technology,” said Paula Stonemetz, Director Diagnostic Business Development, Digital Biology Center, Bio-Rad Laboratories.

The researchers were awarded a National Academy of Clinical Biochemistry (NACB) Distinguished Abstract Award at the 2013 AACC annual conference. The results are part of a larger planned study to determine if cfDNA is the earliest indication of a transplant organ rejection.

Source: EurekAlert!

BIDMC Cardiovascular Institute Researchers Will Lead $4 Million NIH Grant to Study MicroRNAs

A cardiovascular research team from Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH), led by BIDMC Principal Investigator Saumya Das, MD, PhD, has been awarded a $4 million Common Fund grant from the National Institutes of Health (NIH) as part of a newly formed program on Extracellular RNA Communication. The five-year grant will focus on identifying microRNA biomarkers in heart disease.

Each year, complications from heart attacks (myocardial infarctions) contribute to more than half a million cases of heart failure and 300,000 cases of sudden cardiac arrest, when the heart suddenly stops. Both of these conditions are closely related to a process known as remodeling, in which the structure and function of the heart changes – or remodels — following a heart attack.

“Our goal is to explore the role that microRNAs play in predicting which heart-attack patients will go on to experience complications,” explains Das, an electrophysiologist in BIDMC’s Cardiovascular Institute and co-director of the cardiovascular genetics program within the Outpatient Cardiovascular Clinic.

“Current strategies used to identify the highest risk patients have often been inaccurate,” he adds. “We think that a blood test that makes use of microRNA biomarkers could replace existing strategies and more accurately predict which patients might experience poor outcomes and thereby identify who would most benefit from frequent monitoring and medical care.” Other investigators who are part of the NIH grant, “Plasma miRNA Predictors of Adverse Mechanical and Electrical Remodeling After Myocardial Infarction,” include BIDMC Director of Cardiovascular Research Anthony Rosenzweig, MD, and BWH investigators Raymond Y. Kwong, MD, MPH, and Mark Sabatine, MD, MPH.

microRNAs are one type of extracellular RNA. Once considered nothing more than genomic “junk,” microRNAs have more recently been recognized as playing a key role in cellular functions. Several years ago, scientists began to recognize that these small, noncoding RNAs were not only found inside cells, but could also be found in blood and other tissue fluids.

Using patient plasma samples from extensively characterized patients who have suffered heart attacks, the scientific team will first identify which specific microRNAs are related to poor heart remodeling. They will then use cell culture and animal models of heart disease to further prioritize which microRNAs play a functional role in disease progression. Finally, the investigators will validate these prioritized microRNAs as prognostic markers for poor health outcomes after heart attacks in a large prospective clinical trial.

“Ultimately, we think that miRNA-based tests could replace current tests to predict which patients might be at risk of complications and, therefore, be good candidates to receive an implanted defibrillator,” says Das. “At the same time, we hope to be able to better predict which individuals are at less risk of complications – and thereby spare them unnecessary and costly procedures.”

Source: EurekAlert!