Acute kidney injury (AKI) is a rapid loss of kidney function that includes, but is not limited to, acute renal failure.¹ Ninety-four percent of patients with AKI will NOT require renal replacement therapy.²

Three standardized criteria for staging severity of AKI (RIFLE, AKIN, and KDIGO criteria) have been published during the past decade. All definitions use serum creatinine and urine output to diagnose AKI and stratify into three severity levels (mild, moderate and severe). While they are useful for evaluating AKI in epidemiological studies, they can be time consuming and potentially inaccurate to use in routing practice with individual patients. As a result, AKI thus largely remains a clinical diagnosis.¹

Acute kidney injury (AKI) is an increasingly common and potentially devastating complication in hospitalized patients.³ Studies suggest that approximately half of all patients admitted to the ICU will develop some stage of AKI, resulting in stage-wise increased mortality risk.⁴ If a patient develops an AKI complication during hospitalization, short-term and long-term consequences could be twice as severe, such as length of stay (LOS),⁵ hospital cost,⁵ 30-day readmissions⁶ and hospital mortality.⁵

Unlike myocardial infarction, AKI is usually silent without signs and symptoms to help clinicians guide risk assessment.⁷ While a number of acute and patient risk factors for AKI have been identified, there is no reliable way to use this information to establish a clear risk profile.⁷ The current diagnostic paradigm for AKI relies largely on biomarkers known to be insensitive and slow to change after kidney injury, often leading to a late and inaccurate diagnosis of AKI with resultant adverse outcomes.³

The American Society of Nephrology (ASN) has designated the identification of novel AKI biomarkers a top priority.⁸

Challenges in identifying patients at risk can lead to delays in recognizing acute kidney injury (AKI). This can potentially lead to irreversible damage and may explain the high mortality associated with AKI.⁹ Early recognition and management of patients at risk for AKI is paramount since there are no specific therapies to reverse established AKI.¹ Early knowledge that a patient is likely to develop AKI may prompt closer patient monitoring and help prevent permanent kidney damage or death.

The NephroCheck^® Test System is a first-of-its-kind test now commercially available in the United States to help physicians assess a patients’ risk of moderate to severe AKI in the next 12 hours. Astute Medical developed the NephroCheck^® Test, an easy to use and accurate immunoassay that, in 20 minutes, quantitatively measures two urinary biomarkers – tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP-7) – and combines them into a single AKIRisk^® Score.

The NephroCheck^® Test is NOT intended to diagnose AKI.

The NephroCheck^® Test is intended to be used as a risk assessment test in conjunction with clinical evaluation to aid in identifying those patients at risk for developing moderate or severe AKI within 12 hours of patient assessment.

Early recognition and management of patients at risk for AKI is paramount since there are no specific therapies to reverse established AKI.¹

The Astute Medical 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 ICU patients, as an aid in the risk assessment for moderate or severe acute kidney injury (AKI) within 12 hours of patient assessment. The NephroCheck^® Test System is intended to be used in patients 21 years of age or older.

The NephroCheck^® Test, used in conjunction with clinical evaluation, can aid in the risk assessment for moderate or severe acute kidney injury (AKI) within 12 hours of patient assessment. This early knowledge that a patient is likely to develop AKI may prompt closer patient monitoring and help prevent permanent kidney damage or death.

The biomarkers tested in the NephroCheck^® Test are biomarkers of kidney “stress” that are present during the earliest phases of kidney injury:

• Tissue Inhibitor of Metalloproteinase 2 (TIMP-2)
• Insulin-like Growth Factor Binding Protein 7 (IGFBP-7)

Click here for more information on the biomarkers.

Over 300 mechanistically relevant candidate biomarkers were analyzed in two prospective, multicenter, observational clinical trials by clinical researchers and Astute Medical¹⁰:

• 37 geographically diverse clinical sites and more than 1,200 ICU patients
• Included sepsis, shock, major surgery, trauma and other common comorbidities in the intended use population
• Excluded known preexisting moderate-to-severe AKI (patients were enrolled prior to any known major kidney function changes, serum creatinine or urine output, associated with moderate-severe AKI)
• Candidate biomarkers were analyzed by immunoassay in blood and urine collected before major functional changes associated with moderate-severe AKI

The NephroCheck^® Test was validated in two clinical studies (Studies A and B):

• More than 500 patients at 29 sites in the United States
• Patients had diverse reasons for ICU admission (e.g., surgery, sepsis, trauma) and common comorbidities (including CKD, diabetes and heart disease)
• Excluded patients with known preexisting moderate-to-severe AKI (Patients were enrolled prior to any known major kidney function changes, serum creatinine or urine output, associated with moderate-severe AKI)
• A panel of expert nephrologists (blinded to the NephroCheck^® Test results) clinically adjudicated each case as having or not having moderate or severe acute kidney injury in the next 12 hours

The validation studies established the following test performance:

• Significant discrimination between patients with AKI and those without AKI
• High sensitivity and negative predictive value for confidence in identifying the majority of patients at risk for AKI
• No elevation of test results by chronic comorbidities or non-AKI acute conditions (relative to apparently healthy subjects)
• 1 in 4 (study A) to 1 in 3 (study B) patients with a positive test result (AKIRisk^® Score > 0.3) developed AKI in the next 12 hours

The NephroCheck^® Test provides the user with a single numerical result, called the AKIRisk^® Score. This result is provided by the Astute140^® Meter for the NephroCheck^® Test and has a range of 0.04 to 10.0.

The AKIRisk^® Score is calculated by the Astute140^® Meter as the product of the measured concentrations of the two biomarkers, TIMP-2 and IGFBP-7 (measured in ng/mL), divided by 1,000:

The NephroCheck^® Test Result (AKIRisk^® Score) = ([TIMP-2]*[IGFBP-7]) 1000 (units = (ng/mL)²/1000)

A single cutoff of AKIRisk^® Score > 0.3 for the NephroCheck^® Test has been established based on the results from clinical studies to achieve high sensitivity while preserving acceptable specificity. The > 0.3 cutoff allows the clinician to identify the majority of subjects who will manifest moderate or severe AKI within 12 hours. Based upon results from clinical testing, intended use patients with AKIRisk^® Scores ≤ 0.3 are at lower risk of developing moderate to severe AKI within 12 hours of assessment than intended use patients with AKIRisk^® Scores > 0.3.

A single cutoff of AKIRisk^® Score > 0.3 for the NephroCheck^® Test has been established based on the results from clinical studies to achieve high sensitivity while preserving acceptable specificity. The NephroCheck^® Test is designed to identify the majority of subjects who will manifest moderate or severe AKI within 12 hours.

In two studies, the Sensitivity¹¹ of the NephroCheck^® Test was found to be 92% and 76% at the 0.3 cutoff. In these same studies, the Negative Predictive Value (NPV)¹² of the NephroCheck^® Test was found to be 96% and 88% at the 0.3 cutoff. These values mean that the majority of patients who will develop acute kidney injury in the next 12 hours will test positive, and of those patients with a negative test result, only a very small percentage will be at risk of developing acute kidney injury.

In two studies, the Specificity¹¹ of the NephroCheck^® Test was found to be 46% and 51% at the 0.3 cutoff. In these same studies, the Positive Predictive Value (PPV)¹² of the NephroCheck^® Test was found to be at 27% and 31% at the 0.3 cutoff. These results mean that patients with a positive NephroCheck^® AKIRisk^® Score (> 0.3) have a one-in-four to a one-in-three chance of developing moderate or severe AKI within 12 hours of assessment.

High sensitivity and negative predictive value are important qualities of a risk assessment tool to ensure that you identify the majority of patients at risk of developing a disease. The majority of patients who will develop acute kidney injury in the next 12 hours will test positive, and of those patients with a negative test result, only a very small percentage will be at risk of developing acute kidney injury.

The NephroCheck^® Test should be run on ICU patients who currently have or have had within the past 24 hours acute cardiovascular and or respiratory compromise.

The demographics and other baseline information for the intended use patients in Study A is found in the package insert for all subjects and for AKI and No AKI subjects. Click here for the product info.

The NephroCheck^® Test is simple to run, and once the sample is prepared, results can be available quickly – in approximately 20 minutes. The test should be run by the central lab.

The NephroCheck^® Test is commercially available in the United States and select countries in Europe.

To order the NephroCheck^® Test, contact customer service at the following:

Phone: +1 (855) 317-2788
(M–F, 8 a.m. to 5 p.m. PST)
customerservice@astutemedical.com