Urinary Biomarkers Identify First Signs of Kidney Failure in Patients Undergoing Open Heart Surgery
Tuesday June 28, 8:30 am ET
CINCINNATI, June 28 /PRNewswire/ -- A Cincinnati medical research team led by Prasad Devarajan, MD, has reported discovering a series of early biomarkers in urine that may dramatically reduce from 3 days to two hours, the ability to identify the first signs of potential kidney failure in patients undergoing open heart surgeries.
Their research, entitled "Early Prediction of Acute Renal Injury Using Urinary Proteomics," was just published online in The American Journal of Nephrology (2005; 25:318-326). They studied 60 children and young adults undergoing cardiopulmonary bypass operations, according to Dr. Devarajan, The Louise M. Williams Endowed Chair, Professor of Pediatrics and Developmental Biology, and Director of Nephrology and Hypertension at Cincinnati Children's Hospital Medical Center.
Biomarkers are proteins found in blood, saliva or urine, that signal the presence of disease. They are at the center of proteomics, a new growing field involved in the study of all proteins in an organism.
In their paper, the researchers reported identifying four distinct urinary biomarkers that predict acute renal injury using recent advances in proteomics with proprietary technology from Ciphergen Biosystems, Inc (Nasdaq: CIPH - News). The biomarkers detected with the Ciphergen equipment were also confirmed by more conventional methods, prompting Dr. Devarajan and the group to note that this advanced technology which detects proteins captured on protein biochips has emerged as the preferred platform for urinary protein profiling.
"Despite major achievements in treating patients with kidney failure, little has changed in the last four decades to enable early diagnosis of kidney failure before it progresses to a potentially deadly condition," said Dr. Devarajan who cited, in the research paper, that the Ciphergen method is rapid, enabling researchers to identify the key proteins in urine with a turn- around time of only 90 minutes, and requiring only a microliter of urine.
More than 700,000 patients undergo cardiopulmonary bypass operations annually in the US alone, with up to 40 percent of them experiencing some degree of acute renal failure -- considered a common and potentially devastating problem in clinical medicine. Similarly, 10 percent of infants and children with congenital heart disease also experience acute renal failure following cardiac surgery, to the point where they require dialysis for survival.
By identifying the first signs of kidney problems following surgery in a matter of hours, physicians can launch potentially effective therapeutic measures immediately. Currently, doctors measure changes in serum creatinine, a waste product of protein metabolism found in muscle and blood and excreted in normal urine. However, evaluating creatinine levels in the blood is considered an unreliable indicator of sharp changes in kidney function.
The Cincinnati researchers noted that everyone in the study started with normal kidney function and similar urinary proteomic patterns. But for 25 percent of the group, their cardiac operations led to acute renal failure, that was predictable based on each of their biomarker patterns.
Of the 60 participants, who each provided a series of spot urine samples before their surgery and two hours and six hours after their operations, researchers found that 15 subsequently developed acute renal failure. This group had a 50 percent or greater increase in serum creatinine after their operations. Five of the 15 had elevated serum creatinine within the first two days after their operations while the other 10 experienced similar problems 48 to 72 hours after surgery. In striking contrast, all patients who subsequently developed acute renal failure revealed characteristic changes in their urine biomarker patterns within two hours of the surgery.
"In addition to cardiac surgery patients, this method and test could be very useful in the early diagnosis and prediction of kidney injury in a variety of other common clinical situations, including kidney transplantation, abdominal surgery, trauma, bleeding, shock, myocardial infarction, stroke, sepsis, and the use of nephrotoxic medications such as antibiotics and chemotherapy," said Dr. Devarajan.
For more information about the study contact:
Amy Reyes,
Media Relations Manager
Cincinnati Children's Hospital
Medical Center
513-636-9684
amy.reyes@cchmc.org
For more information about Ciphergen Biosciences, Inc., contact:
Ronald Rosenberg
Lehman Millet
60 Canal
Boston, MA 02114
617-722-0019 x 3275
ronald_rosenberg@millet.com
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Abstract of the journal article
Jason
content.karger.com
Aims: The lack of early biomarkers for acute renal failure (ARF) has crippled our ability to launch potentially effective therapeutic measures. We tested the hypothesis that urinary proteomics could identify novel early biomarker patterns for ischemic renal injury. Methods: Sixty patients undergoing cardiopulmonary bypass (CPB) were enrolled. Urine samples obtained at 2 and 6 h post CPB were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). The primary outcome variable was ARF, defined as a 50% or greater increase in serum creatinine. Results: Fifteen patients (25%) developed ARF 2-3 days after CPB. SELDI-TOF-MS analysis of urine from the ARF group at baseline versus at 2 and 6 h post-CPB consistently showed a marked and statistically significant enhancement of protein biomarkers with m/z of 6.4, 28.5, 43 and 66 kDa. The same biomarkers were enhanced when comparing control versus ARF groups at 2 and 6 h post-CPB. The sensitivity and specificity of the 28.5-, 43- and 66-kDa biomarkers for the prediction of ARF at 2 h following CPB was 100%. The receiver operating characteristic curves revealed an area under the curve of 0.98. Conclusion: SELDI-TOF-MS is a novel, non-invasive, sensitive, highly predictive, reproducible, rapid method for the prediction of acute renal injury following CPB.
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