The importance of early detection in stopping acute kidney injury

Acute kidney injury (AKI) is as serious and common as a heart attack, and it can strike without any warning signs or symptoms. It affects as many one in five hospital patients in the United States¹ and can rapidly develop into chronic kidney disease (CKD) or kidney failure, leading in more severe cases to the need for permanent dialysis treatment with compromised quality of life or even to death. Sometimes called a silent killer, AKI is often overlooked as the true cause of mortality. AKI is also one of the costliest health issues both in the U.S. and around the world.

Compounding the problem is that the medical community has been slow to recognize the disease and implement a standard of care. However, recent developments and research have led to new testing that can detect AKI much earlier than other commonly used tests and is expected to improve clinical and economic outcomes for patients and hospitals.

What is AKI?

AKI is the rapid deterioration of kidney function within hours or days. It is often diagnosed in the context of other acute illnesses.² It indicates initial subclinical kidney cell injury that can be reversible if the condition is detected early, before dysfunction. AKI is most commonly brought on by an influx of drugs or toxins or contrast-induced substances, a blockage of urine, serious infection, trauma, acute heart failure, major surgery, or chronic illness. Up to 50 percent of critically ill patients will develop some stage of AKI.³ Patients most at risk are those in intensive care, as well as the elderly and diabetic patients.

AKI can cause the accumulation of waste products, electrolytes, and fluid in the body as well as reduced immunity and dysfunction of other organs.² Prevention through proper testing is the best measure to address AKI. Treatment of AKI can include many different therapeutic strategies such as reducing the intake of antibiotics or other drugs, managing fluids and diuretic dosages, and monitoring urine output. Other treatments or surgeries could be delayed until the kidneys are functioning normally. If detection of the risks of AKI occurs early enough and changes to treatment are made, the kidneys can sometimes normalize themselves; consequently, it is crucial to immediately recognize all phases of AKI occurrence.

More cases, more costs

While AKI is a preventable disease, it is a growing problem around the world. A 2014 report by the National Confidential Enquiry into Patient Outcome and Death (NCEPOD), a London-based nonprofit that reviews the management of patients through research and surveys, found that 30 percent of AKI cases that occurred during hospital admission were avoidable. The same report established that only 50 percent of patients with AKI received an overall standard of care considered good. Rates for AKI and mortality in ICU patients with AKI are quite similar across the continents. Current strategies to reduce AKI in developed countries have been found to be ineffective or have not been adequately implemented. It is also remarkable that the different levels of healthcare systems across the continents, from the most to the least advanced, do not influence the mortality rate of AKI.

AKI has been known to the medical community for at least the past century. Over the past two decades, however, the availability of electronic health records and large cohorts of patients with AKI have made studying the disease in different settings possible. Studies show that both the number of cases and the severity of the disease have been increasing. People are living longer, so there are more patients at risk of developing AKI worldwide, particularly those with chronic conditions and those undergoing major surgery. As a result, there have been rapid increases in the incidence of AKI reported, highlighting a growing impact on the public health burden of advanced kidney disease in the U.S. and beyond. In fact, a 2014 study published in Kidney International showed that AKI occurs in 18 percent of all general hospitalizations and up to 50 percent of all ICU cases worldwide.⁴ AKI cases requiring dialysis have also become more prevalent.⁴

The mortality rate of hospitalized patients with AKI is remaining steady, continuing to be high at about 50 percent.⁵ In the U.S. alone, AKI is responsible for two million deaths per year⁶ and $10 billion in costs to the healthcare system.⁷ The later AKI is detected, the greater the associated costs. For patients, AKI can lead to longer hospital stays and higher hospital bills, particularly when they are referred to chronic dialysis treatment. As a consequence, for hospitals detecting AKI early is critical to improving care and patient outcomes and reducing costs.

Despite the disease’s prevalence and severity, AKI awareness among patients and those in the medical community, including doctors and hospital administrators, is still relatively low. AKI has been identified by different methodologies, and there was no standardization of care until 2012, when the global nonprofit Kidney Disease Improving Global Outcomes (KDIGO), dedicated to improving the care and outcomes of kidney disease patients around the world, created the KDIGO Clinical Practice Guidelines for Acute Kidney Injury. This development has contributed to more widespread discussion and awareness about the disease.

Testing is the answer

Addressing both the clinical and economic concerns related to AKI requires prevention by early detection and treatment of patients at risk for developing the disease. Since 1917, the way to test for AKI has been by serum creatinine (SCr). Today, AKI is still most commonly detected by SCr and urine output tests, based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease), AKIN (Acute Kidney Injury Network), or KDIGO methods. The problem with using SCr for detection of AKI, however, is that the diagnosis comes too late. The time required to detect a rise in SCr as a consequence of kidney damage is 24 to 48 hours, and during this period of initial renal cellular damage, before SCr rises, almost 50 percent of kidney function can be lost.⁸ Serum creatinine levels also can be abnormal due to factors that are not related to kidney function, since it is coming as degradation of muscle cells, and from the liver, independent of kidney function.

The SCr and urine output tests measure the function of the kidney, so it should be noted that these tests detect dysfunction, not injury. Because of this, the medical community has been able to diagnose the disease only after the kidney has been damaged and there is already a higher risk of mortality. The goal should be to identify patients who are suffering an injury, so clinicians can intervene and remove the cause of the injury before it causes dysfunction.

One assay that recently became commercially available in the U.S. and Europe detects injury before the loss of function. It is a urine test that provides lab results in 16 minutes, allowing clinicians to assess the risk of AKI and proactively intervene before damage occurs. While SCr is a filtration function marker, the new test measures the TIMP2 and IGFBP7 proteins that are upregulated in response to cellular/tissue injury. Compared to SCr, the new test is more sensitive, accurate, and, mostimportant, faster in indicating AKI.

Biomarkers are traditionally identified through theoretical discovery but are often proven not to have viable applications in a clinical setting. The discovery of the TIMP2 and IGFBP7 biomarkers was different in that it was the result of a dedicated study created to identify and validate new biomarkers of AKI. The study isolated a group of more than 522 critically ill adults in three distinct cohorts—including patients with sepsis, shock, trauma, and major surgery—and a comparison group, and examined more than 300 biomarkers. As a result, the two novel biomarkers, the TIMP2 and IGFBP7, were clinically validated as the best indicators of patients at risk for AKI.

All healthcare professionals need to know that AKI is detectable and preventable. Incorporating best practices and new methods for testing for AKI should be part of any quality care protocol. Improving the clinical and economic outcomes of AKI begins with detection.

REFERENCES

1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Kidney Inter., Suppl. 2012;2:1-138.1.
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3. Mandelbaum T, Scott D, Lee J, et al. Outcome of critically ill patients with acute kidney injury using the AKIN Criteria. Crit Care Med. 2011;39(12)2659-2664.
4. Siew ED, Davenport A. The growth of acute kidney injury: a rising tide or just closer attention to details? Kidney Int. 2015;87(1):46–61.
5. Ympa YP, Skar Y, Reinhart K, Vincent JL. Has mortality from acute renal failure decreased? A systematic review of the literature. Am J Med. 2005;118(8):827-832.
6. Ali T, Khan I, Simpson W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol. 2007;18(4):1292-1298.
7. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005:16:3365-3370.
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Salvatore Di Somma, MD, serves as Director Emergency Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea Hospital Rome. He is also an Associate Professor of Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, Department of Medical-Surgery Sciences and Translational Medicine, and Chairman Postgraduate School of Emergency Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome.