Clinical Progress Note: Pediatric Acute Kidney Injury

The renal angina index (RAI) identifies critically ill children at high risk for AKI. The RAI combines traditional markers of AKI, such as a change in estimated creatinine clearance and fluid overload, with patient factors, including need for ventilation, inotropic support, and history of transplantation (solid organ or bone marrow) to identify those patients who are at high risk for severe AKI. Patients identified as high risk by the patient factors component of the RAI have a much lower threshold for both a decrease in creatinine clearance and fluid overload to be considered at risk for severe AKI, as these early signs are more likely to reflect an early impending severe AKI in this high-risk group. Conversely, patients that do not meet these patient factors are more likely to simply have a transient or functional AKI, and therefore have a higher threshold for both a change in creatinine clearance and fluid overload in order to be considered at high risk for severe AKI.

The RAI has been validated in the critical care setting as a method to predict severe AKI at day three of admission to the pediatric intensive care unit, with a negative predictive value of 92%-99% when the score is negative in the first 12 hours.¹⁰ In selected high-risk patients (RAI ≥ 8), biomarkers become even more reliable for AKI prediction (eg, injury markers have an excellent area under the receiver operating characteristic curve (AUC) of 0.97 for severe AKI prediction in this high-risk group).¹¹ While only validated for critically ill patients, the concept of renal angina is still applicable in the complex populations managed by hospitalists who practice outside of the intensive care unit setting. Early signs of renal dysfunction (eg, rising SCr, fluid overload ≥5%) in patients with risk factors (see below) should prompt a thorough evaluation, including urinalysis, daily SCr, nephrotoxin avoidance, and tissue injury biomarkers, if available.

The risk factors for AKI are numerous and tend to potentiate one another. The most frequent predisposing comorbidities include CKD, heart failure or congenital heart diseases, transplantation (bone marrow or solid organs), and diabetes. Disease-related factors include sepsis, cardiac surgery, cardio-pulmonary bypass, mechanical ventilation, and vasopressor use. Potentially modifiable factors include hypovolemia and multiple nephrotoxic exposures. ^2,3

Nephrotoxic medications are now among the most common causes of AKI in hospitalized children.¹² Approximately 80% of children are exposed to at least one nephrotoxin during an inpatient admission.¹² Exposure to a single nephrotoxic medication is sufficient to place a child at risk of AKI, and each additional nephrotoxin further increases the risk.¹² While some drugs are routinely recognized to be nephrotoxic (eg, ibuprofen), others are commonly overlooked, notably certain antibiotics (eg, cefotaxime, ceftazidime, cefuroxime, nafcillin, and piperacillin) and anticonvulsants (eg, zonisamide).¹² Furthermore, the combination of multiple nephrotoxins can potentiate the risk of AKI. For example, the combination of vancomycin and piperacillin/tazobactam increases the risk of AKI by 3.4 times compared with the combination of vancomycin with another antipseudomonal beta-lactam antibiotic.¹³

Adequate monitoring, including daily SCr measurements and risk awareness, are critical as nephrotoxin-associated AKI can be easily missed in the absence of routine SCr monitoring, especially since these children are typically nonoliguric¹². Quality improvement efforts focused on obtaining daily SCr in patients exposed to either three or more nephrotoxins or three days of either aminoglycoside or vancomycin, even without concomitant exposure to other nephrotoxins, have shown success in decreasing both the number of nephrotoxins and the rate of nephrotoxin-associated AKI.¹²

While a significant injury cannot always be avoided, a mindful clinical approach and management can help to prevent some complications of AKI. An awareness of fluid status is critical, as fluid overload greater than 10% of the patient’s weight independently increases the risk of mortality in both adults and children.¹⁴ To assess the risk of AKI progression and potential failure of conservative management with diuretics, a furosemide stress test (FST) is an easy, safe, and accessible functional assessment of tubular reserve in a patient without intravascular depletion.¹⁵ A growing body of literature in adults shows that FST-responders are less likely to progress to stage 3 AKI or need renal replacement therapy than nonresponders.¹⁵ The FST is currently being investigated and standardized in children.