Acute kidney injury (AKI) is a serious medical condition where the kidneys suddenly stop working, often occurring in hospitalized patients. The severity of AKI ranges from minor dysfunction to complete kidney failure requiring dialysis, and it is a major factor in extended hospital stays, particularly in the Intensive Care Unit (ICU).
Traditional methods, such as monitoring serum creatinine levels, are often too slow because creatinine levels do not increase until a significant portion of kidney function is lost, sometimes taking 12 to 48 hours to show a change. This time lag means diagnosis frequently happens after injury has occurred, limiting the opportunity for early, protective interventions. The NephroCheck test detects kidney stress and the risk of moderate to severe AKI hours or even days before traditional indicators signal a problem.
The Silent Threat of Acute Kidney Injury (AKI)
AKI is defined by a sudden decline in the kidneys’ ability to filter waste products from the blood, leading to a buildup of toxins and an imbalance of electrolytes and fluids. While AKI can be reversible if caught in its earliest stages, its presence significantly increases the risk of long-term complications, including the development of chronic kidney disease. The mortality rate for critically ill patients who develop severe AKI can be substantial.
The development of AKI is often triggered by an acute medical event that reduces blood flow to the kidneys or introduces toxic substances that directly harm the kidney cells. Common causes include severe infections leading to sepsis, major cardiac or non-cardiac surgery, and conditions that cause severe dehydration or shock. In these scenarios, the kidney is subjected to intense stress, which can quickly transition into measurable injury without an immediate warning sign.
Patients experiencing these acute insults are vulnerable, making early prediction a high priority for clinicians. The lack of reliable, real-time diagnostic markers has historically hampered efforts to intervene proactively, relegating treatment largely to supportive care after the damage is already established. This inability to predict AKI has driven the search for new biomarkers that can signal cellular distress before a measurable loss of kidney function occurs.
Decoding the NephroCheck Test
The NephroCheck test is a diagnostic tool that identifies patients at high risk of developing moderate to severe AKI within the next 12 hours. The test operates by measuring the concentration of two specific protein biomarkers in a simple urine sample: Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) and Insulin-like Growth Factor-Binding Protein 7 (IGFBP-7). These two proteins are not routinely checked in traditional blood or urine tests, but their presence indicates that kidney cells are under significant stress.
TIMP-2 and IGFBP-7 are collectively known as “cell cycle arrest” biomarkers because they are released by the tubular cells of the kidney when an injury or stressor is detected. The release of these proteins triggers a protective mechanism that causes the kidney cells to halt their normal growth and division cycle in the G1 phase. This pause prevents the replication of potentially damaged cells, allowing time for repair.
The test result is reported as a single numerical value, called the AKIRisk Score, which is calculated from the product of the two biomarker concentrations, expressed as \([(text{TIMP-2}) times (text{IGFBP-7})]/1000\). This combined score provides a quantitative index of the severity of the kidney’s cellular stress response. The process is relatively quick, with results obtained in approximately 20 minutes, aiding rapid decision-making in acute care settings.
Identifying High-Risk Patients
The NephroCheck test is intended for use in patient populations where the likelihood of developing AKI is elevated. The FDA-cleared use is for patients 21 years of age or older who are in the Intensive Care Unit (ICU) and have experienced acute cardiovascular or respiratory compromise within the past 24 hours. These patients are often dealing with conditions that place a high strain on the kidneys, such as septic shock, severe heart failure, or major trauma.
Specific clinical scenarios have been identified where the test provides the most actionable information, including patients undergoing major non-cardiac surgery or complex cardiac procedures, such as coronary artery bypass grafting. For instance, patients undergoing cardiac surgery face a significant risk of AKI due to the use of a heart-lung machine and periods of reduced blood flow, making the NephroCheck test a valuable tool for preoperative and immediate postoperative risk stratification.
The goal in these settings is proactive screening, which contrasts sharply with the reactive nature of serum creatinine monitoring. By identifying patients who are highly vulnerable to AKI due to their existing condition or planned procedure, clinicians can implement preemptive strategies. The test provides an early warning to focus resources and protective measures on patients heading toward kidney injury, rather than treating all high-risk patients uniformly.
Interpreting Test Results and Clinical Action
The AKIRisk Score results are stratified into three categories, which guide subsequent clinical management. A score of less than \(0.3 (text{ng/mL})^2/1000\) indicates a low risk of developing moderate to severe AKI within 12 hours, with an estimated absolute risk of less than 5%. Patients in this category typically continue with standard ICU care, with no immediate need for aggressive preventative measures.
An intermediate risk is indicated by a score between \(0.3\) and \(2.0 (text{ng/mL})^2/1000\), where the risk of developing moderate to severe AKI increases to a range of 15% to 25%. Scores above \(2.0 (text{ng/mL})^2/1000\) signal a high risk, with the probability of developing moderate to severe AKI within 12 hours reaching 40% to 66%. These higher-risk scores prompt an immediate shift in the patient’s management strategy toward maximal kidney protective care.
Clinical actions taken based on a positive or high-risk score include preventative interventions designed to reduce stress on the kidneys. This often involves optimizing the patient’s fluid balance, adjusting or temporarily stopping medications that are known to be toxic to the kidneys, and ensuring blood pressure is maintained within an optimal range. The test facilitates a timely, preventative response, allowing for intervention before the patient meets the criteria for an established AKI diagnosis.