SAN DIEGO – July 12, 2017 – For critically ill hospital patients, no matter what the primary health problem, one of the most serious and frequent complications clinicians worry about is acute kidney injury, which is damage to the kidneys that impairs their ability to clear toxins from the blood and produce urine.1 Acute kidney injury (AKI) can progress without symptoms for hours to days and makes everything at least twice as bad for the patient: increased length of hospital stay,2 increased risk of long-term complications3 and increased risk of death.2 AKI kills an estimated 2 million people worldwide annually, and that number continues to grow.4
AKI has frustrated physicians for years because until recently there’s been no reliable way to determine which critically ill patients were at risk or in the earliest stages of injury. As a result, “it just seemed an inevitable outcome that some patients were just going to get AKI,” said Adan Mora, M.D., F.C.C.P., an intensivist at Baylor University Medical Center in Dallas. “It’s a big deal for us in the ICU when the kidneys fail because of the high mortality associated with this,” Dr. Mora said.
AKI is a risk for many patients. “It’s definitely a bad actor for cardiac surgery,” said V. Seenu Reddy, M.D., a cardio thoracic surgeon at Centennial Medical Center in Nashville. “It’s a very serious complication and can affect the outcome of major cardiac surgical procedures,” Dr. Reddy said.
The challenge, historically, has been a lack of biomarkers, or symptoms within the body that indicate the kidneys are stressed and at risk of failure, Dr. Mora said. Obvious biomarkers or symptoms could alert physicians to impending danger and allow them to stay ahead of the problem. Such tests exist for heart attacks and other organ failures, however, the indicators clinicians rely upon for kidney trouble, urine output and serum creatinine, often aren’t present until kidney damage has already occurred, Dr. Reddy said. And if these indicators are present they aren’t always reliable because of variables, such as a patient’s muscle mass and fluid intake, as well as inconsistency in how these are measured, he said.
Mora and Reddy are among a group of doctors who are leading a change in medicine to focus on stress to the kidneys with the help of a new test that has been shown to improve patient outcomes.
The NephroCheck® Test measures two biomarkers that indicate kidney stress, TIMP-2 and IGFBP-7,5 enabling clinicians to proactively identify patients who are at risk for AKI.6 Studies have demonstrated the biomarkers’ effectiveness in multiple patient populations, including those with sepsis,7 pre-existing conditions8 and those who have undergone cardiac and other major surgery.9
Earlier this year German researchers reported in a published study that by using the NephroCheck® Test to identify high-risk patients and then implementing a bundle of care recommended by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, they were able to reduce the occurrence of moderate to severe AKI by nearly 35 percent.9
Dr. Reddy said he began using the test after reading several studies about the biomarkers and realizing there was a new tool by which he could try to deliver better outcomes and better care for heart surgery patients.
“A heart surgery program is measured on the quality of outcomes, including the avoidance of renal failure, which is second only to stroke as a dangerous complication,” he said. “Many heart programs are adopting best practices, so to remain a top program in the country I feel that as new tools become available to provide better outcomes and avoid unnecessary complications, we should seek to evaluate them carefully to possibly include them in our care pathway.”
Reddy’s patients often have multiple risk factors in addition to their heart disease, such as high blood pressure, atherosclerosis and diabetes, which means the patient can be starting out with underlying medical conditions that make them more prone to kidney injury.
The doctor has used the NephroCheck® Test after surgery to quickly determine whether a patient’s kidneys were under significant stress. Knowing the kidneys are under stress may lead him to alter his normal postoperative treatment, which could include adjusting the amount of fluids given to the patient or the drugs used to support the patient’s blood pressure, which may positively impact the kidneys, he said.
Reddy said he has also used the test in elderly patients who undergo a procedure in which an aortic valve is replaced through a catheter (TAVR), which involves the administration of contrast agents during the procedure. The contrast agents can impact these often frail and “elderly” kidneys more so than those in younger patients. Having access to the biomarkers may serve as an early warning system.
Mora said he recently had a 50-year-old man admitted to the ICU with flu and pneumonia. The doctor considered giving the patient medication that would have increased his blood pressure, which could impact the kidneys. Additionally, the doctor needed to decide whether the patient needed fluids, which would impact the kidneys.
“With the traditional markers it looked as though the patient could tolerate those treatments, but when I conducted the test it said the patient was in the danger zone for AKI,” Mora said. “This caused me to change things I normally would have done to spare any additional insult to the kidney.”
He’s also used the test on patients he thought might already be experiencing kidney stress before proceeding with a treatment, such as forcing fluids or use of a diuretic, that could harm the kidneys.
“In one such case I found that a patient was not in stress and could handle the treatment plan well,” he said.
“These biomarkers, this test, challenge us to think about treatment in a different way. It will absolutely allow us to improve outcomes, reduce morbidity and mortality of patients in the ICU. I think it’s going to be a game-changer,” he said.
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1National Kidney and Urologic Diseases Information Clearinghouse. The Kidneys and How They Work [accessed 2017 June 8]. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/.
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3Chawla LS, Eggers P, Star R. Acute Kidney Injury and Chronic Kidney Disease as Interconnected Syndromes. N Engl J Med. 2014;371:58-66.
4Murugan R, Kellum JA. Acute kidney injury: what’s the prognosis? Nat. Rev. Nephrol. 7, 209–217 (2011); published online 22 February 2011; doi:10.1038/nrneph.2011.13.
5Kellum JA, Chawla LS. Cell-cycle arrest and acute kidney injury: the light and dark sides. Nephrol Dial Transplant (2015) 0: 1–7doi: 10.1093/ndt/gfv130.
6Bihorac A, Chawla L, Shaw A, et al. Validation of Cell-Cycle Arrest Biomarkers for Acute Kidney Injury Using Clinical Adjudication. Am J Respir Crit Care Med. Vol 189, Iss 8, pp 932–939, Apr 15, 2014.
7Honore PM, Nguyen HB, Gong M et al. Urinary Tissue Inhibitor of Metalloproteinase-2 and Insulin-Like Growth Factor-Binding Protein 7 for Risk Stratification of Acute Kidney Injury in Patients With Sepsis. Critical Care Medicine. Published Online June 28, 2016.
8Heung M, Ortega L, et al. Common chronic conditions do not affect performance of cell cycle arrest biomarkers for risk stratification of acute kidney injury.Nephrol Dial Transplant. (2016) 0: 1–8.
9Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: The PrevAKI randomized control trial. Intensive Care Med. (2017) Jan 21.