SAN DIEGO – December 27, 2017 – Hospital clinicians have long been frustrated by the prospect of intensive care unit (ICU) patients developing acute kidney injury (AKI), a stealthy and potentially deadly condition that can arise from renal insults stemming from treatments and care intended to help patients. The complication may be avoidable if clinicians can identify those at risk and apply countermeasures, but they lacked reliable tools to do so until the introduction of Astute Medical’s NephroCheck Test, which measures urinary biomarkers linked to AKI, said Daniel T. Engelman, M.D., associate professor of surgery at the University of Massachusetts-Baystate.
Patients in the ICU are frequently exposed to measures that could be potentially harmful to renal function, often simultaneously and/or in succession, including medications, transfusions and efforts to maintain hemodynamic stability, said Engelman. These renal insults can include broad-spectrum antibiotics used to fight infection in the ICU.
According to Astute Medical, a multicenter study recently published online in the journal Critical Care Medicine showed the NephroCheck Test detected sharp rises in levels of biomarkers indicative of AKI risk on the first day of exposure to broad-spectrum antibiotics vancomycin and piperacillin/tazobactam in patients who developed moderate-to-severe AKI within 48 hours. The study also showed distinct biomarker level increases indicating when major surgery and nonsteroidal anti-inflammatory drugs put patients at risk of AKI. The biomarkers did not elevate at any time following exposure to the same renal insults in patients who did not develop AKI within 48 hours of exposure.
“Early use of the biomarkers could potentially help clinicians to identify patients with renal stress who may benefit from early intervention to prevent progression of kidney injury,” wrote the study authors.
This hypothesis may be borne out as more clinicians put the test into practical use. “The biomarkers provide an early-warning for AKI by telling us when the kidneys are stressed by any of these insults and not yet injured,” Engelman said. “It’s like decades ago when we figured out that cardiac enzymes can show when someone is in the early stages of having a heart attack. It directly impacts the quality of patient care and safety because it gives clinicians more information to determine how to direct our attention and resources properly,” he said.
Identification of patients at risk of AKI can help advance quality of care by improving AKI outcomes, shortening hospital stays, including time in the ICU, and reducing costs, as shown by randomized controlled trials. A recent estimate of AKI-associated increases in U.S. hospitalization costs ranged from $5.4 billion to $24.0 billion, while a study published last month in the Clinical Journal of the American Society of Nephrology reported that the incremental cost of AKI in Canada was approximately CAN $200 million a year, with hospital stays for patients with Stage 2 and Stage 3 AKI averaging 14 days with an average cost of CAN $17,817.
Results from the study published in Critical Care Medicine suggest that testing to assess risk of AKI could also be useful in determining when to move patients from the ICU to a lower care unit, Engelman said. In the study,1 surgery patients’ biomarkers peaked at 24 hours. This correlates with how Engelman said the NephroCheck Test is used in a Springfield, Massachusetts hospital where he performs surgery. Routinely, on the day after surgery, clinicians there evaluate whether the patient is ready to leave the ICU, and its higher levels of monitoring and nursing care, for a step-down unit that allows the removal of many lines, catheters and monitors, he said.
“The biomarkers alert us that a patient might not be doing as well as we thought and may not be ready to make that move, but requires more attention to maintain their stability for a little longer,” he said. “And it allows us to move the other 80 percent of patients out of the ICU with no delay, injury or increased costs,” he said.
The study results also help clinicians understand how a patient’s exposure to a renal insult may relate to the timing and need for further testing, said John Kellum, M.D., a critical care physician, past president of the Acute Dialysis Quality Initiative (ADQI) and an author of the study.
“If I’m faced with a patient who’s had an exposure and I may want to do a urine or blood test, I need to understand how those tests relate to each other in specific ways, not just in ideal cases, and that’s what this study does,” Kellum said.
The negative predictive value of the test is another important finding, he said.
“Now we know that very few patients without an increase in the biomarkers will go on to develop AKI. If I gave a potentially nephrotoxic drug such as vancomycin to a patient and the test results are negative, I have confidence I’m not hurting the patient’s kidneys as a result of the drug. I might have to test again later, but it helps me with regard to determining the patient’s treatment,” he said.
AKI, which has no obvious symptoms, strikes up to half of critically ill patients and has been linked to longer hospital stays and a tenfold increase in mortality. Recent clinical articles have called for the pursuit of innovative strategies to combat AKI, calling it a major public health concern.3
The NephroCheck Test measures levels of the urinary biomarkers TIMP-2 and IGFBP7, which play a role in cell-cycle arrest, a protective mechanism that prevents stressed cells from dividing in case of DNA damage.
The current standard measurement for AKI is serum creatinine levels, which often do not increase for at least 24 hours, after kidney damage has already occurred. “In a nutshell, this has been the problem,” Engelman said.
About Astute Medical
Astute Medical is dedicated to improving the diagnosis of high-risk medical conditions and diseases through the identification and validation of protein biomarkers that can serve as the basis for novel diagnostic tests.
The Company’s focus is community- and hospital-acquired acute conditions that require rapid diagnosis and risk assessment. Astute Medical’s current areas of interest include abdominal pain, acute coronary syndromes, cerebrovascular injury, kidney injury and sepsis.
Astute Medical is a founding corporate partner of 0by25, a human rights initiative aimed at eliminating preventable and treatable deaths from AKI worldwide by 2025.
Astute Medical’s NephroCheck Test received 510(k)-clearance through the FDA’s de novo classification. The test is CE-marked and available in Europe. For additional information, please visit AstuteMedical.com.
The NephroCheck Test Intended Use (United States)
The NephroCheck Test System is intended to be used in conjunction with clinical evaluation in patients who currently have or have had within the past 24 hours acute cardiovascular and or respiratory compromise and are intensive care unit (ICU) patients as an aid in the risk assessment for moderate or severe AKI within 12 hours of patient assessment. The NephroCheck Test System is intended to be used in patients 21 years of age or older.
For more information on the NephroCheck Test visit NephroCheck.com.
Astute Medical®, the AM logo, ASTUTE140®, NephroCheck®, the NephroCheck® logo, and AKIRisk® are registered trademarks of Astute Medical, Inc. in the United States. For information regarding trademarks and other intellectual property applicable to this product, including international trademarks, please see www.astutemedical.com/about/intellectualproperty. PN0654 2017/12/18
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2 Göcze I, Jauch D, Götz M, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK Study. Ann Surg. Published online August 29, 2017.
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