Pediatric Acute Kidney Injury After Noncardiac Surgery: Another Vulnerable Population

See Article, p 332 Acute kidney injury (AKI) is a potentially devastating complication in critically ill neonates and children, with an incidence of up to 30% observed in multinational studies.1,2 Pediatric AKI is associated with deleterious short- and long-term effects, including a more extended stay in the intensive care unit, more prolonged mechanical ventilation, and more frequent chronic kidney disease progression.2,3 Severe AKI has been shown to confer a stepwise increase in critically ill children’s mortality risk.2 Cardiac surgery is a leading cause of postoperative AKI in children. Twenty to 40% of children undergoing cardiac surgery with cardiopulmonary bypass develop some degree of AKI.3,4 Specific populations, including neonates, single-ventricle patients, Fontan palliations, and cardiac transplantations, are particularly vulnerable.3 Whereas extensive epidemiologic data exist on pediatric cardiac surgery–associated AKI, data on AKI after noncardiac surgery are scarce. In this issue of Anesthesia & Analgesia, Wingert et al report the results of a single-center observational study of the prevalence, risk factors, and outcomes of AKI after pediatric noncardiac surgery.5 The study cohort consisted of 8924 surgical cases that occurred over 5 years. The prevalence of postoperative AKI in the first 7 days, as defined by Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine (SCr) criteria, was 3.2% (confidence interval [CI], 2.9-3.6). AKI stages 1, 2, and 3 had prevalence of 1.8%, 1.2%, and 0.2%, respectively. American Society of Anesthesiologists physical status (ASA-PS) was the only perioperative factor significantly associated with developing postoperative AKI (P < .001). Postoperative AKI after pediatric noncardiac surgery was independently associated with increased risk of mortality, with a hazard ratio of 3.28 (CI, 1.71-6.32; P < .001), and 30-day readmission, with a hazard ratio of 1.55 (CI, 1.08-2.23; P = .018). The study by Wingert et al5 is the first to highlight the incidence and burden of AKI in pediatric noncardiac surgery. According to their observations, nearly 1 in 31 children who underwent noncardiac surgery at their institution developed postoperative AKI. Although the prevalence of AKI in their cohort was not surprisingly lower than that previously reported in critically ill children and children following cardiac surgery, their findings reveal that children undergoing noncardiac surgery are also at risk of developing AKI. The investigators must be commended for their robust analysis to examine the association between AKI and outcomes, incorporating propensity score–matched controls and a multivariable Cox proportional hazards regression model to reduce observed confounding. The study also has limitations. First, as acknowledged by the authors, the study was conducted at an academic center where the surgical patients had significant comorbidities, and therefore, their findings cannot be readily generalized to healthy children undergoing routine surgeries. Second, the reported AKI prevalence may underestimate the true prevalence because the investigators could not use urine output (UOP) criteria, which increases sensitivity for pediatric AKI.2 Third, excluding the patients who did not have a baseline SCr may have caused selection bias. The included patients may have had a preoperative SCr because they had a comorbid condition, which increased their risk of developing AKI. Fourth, the investigators broadly characterized operative procedures by surgical and procedure site, and this strategy fails to account for the intrinsic surgical risk associated with specific surgical procedures.6 Finally, the investigators did not assess several perioperative factors associated with pediatric AKI, including fluid balance, anemia, and exposure to nephrotoxic and vasoactive medications. The KDIGO criteria, which rely on increased SCr concentration and oliguria, do not permit timely and accurate AKI diagnosis in the postoperative period. Neither SCr nor UOP is sensitive or specific for AKI. SCr becomes elevated after a significant decrease in glomerular filtration rate (GFR), and the increase may lag behind an insult by as much as 72 hours.7 Also, perioperative factors unrelated to kidney injury and reduced GFR, such as malnutrition, low muscle mass, muscle injury, and fluid overload or depletion, may alter SCr concentration. For example, a child who has intravascular volume depletion in the postoperative period may have a transient elevation in SCr due to normal physiologic response. This child is likely to have a functional pre-renal AKI, which resolves quickly with rehydration, rather than intrinsic kidney injury resulting in a prolonged elevation in SCr. The duration of SCr elevation, though not included in AKI criteria, correlates with the severity of the renal insult.8,9 Oliguria may also be an appropriate physiologic response of functioning kidneys to prolonged fasting, hypovolemia, and perioperative stress.10 Because of the limitations of SCr and UOP in detecting AKI, extensive research has sought to discover alternative biomarkers. Neutrophil gelatinase lipocalin molecule (NGAL) and the combination of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein-7 (TIMP-2 x IGFBP-7) are urinary markers of kidney damage and stress and sensitive predictors of AKI in specific patient populations.11 Given the complex pathophysiology and heterogeneous nature of AKI,12 biomarkers have performed inconsistently in diverse patient populations and have not gained widespread clinical use. For pediatric anesthesiologists to prevent and treat AKI, they must identify patients with significant risk. An AKI risk assessment methodology, called the renal angina index, combines validated clinical risk factors with signs of kidney dysfunction to predict severe AKI and guide biomarker testing in critically ill children.13 An astute reviewer of this editorial proposed that ASA-PS could be integrated with other perioperative risk factors to create a similar AKI risk score for pediatric surgery. As shown in the Table, Wingert et al observed that ASA-PS is strongly associated with AKI risk following pediatric noncardiac surgery. The children classified as ASA-PS III, IV, and V had approximately a 4-, 13-, and 20-fold greater risk than those with ASA-PS I and II. Table. - Relationship Between ASA-PS and AKI ASA-PS No. of patients with AKI No. of patients total % Patients with AKI I 6 1185 0.5 II 36 2798 1.3 III 182 4465 4.1 IV 58 433 13.4 V 6 28 21.4 Abbreviations: AKI, acute kidney injury; ASA-PS, American Society of Anesthesiologists physical status. It is not surprising that AKI complicates the postoperative course of children who undergo major surgery. Future use of a perioperative risk score and sensitive and specific biomarkers may allow for early detection of AKI and initiation of preventative strategies to make pediatric surgery safer for all organs. DISCLOSURES Name: Douglas B. Atkinson, MD. Contribution: This author helped write and edit the manuscript. Name: James A. DiNardo, MD. Contribution: This author helped write and edit the manuscript. This manuscript was handled by: Alexander Zarbock, MD.