Changing the Paradigm in Pediatric Acute Kidney Injury

n this issue of The Journal, Misurac et al1 provide a singledeveloped chronic kidney disease (CKD). The cost and popcenter tertiary care retrospective analysis of nonsteroidal ulation health impact of pediatric patients who progress from anti-inammatory drug (NSAID)-associated acute kidney AKI to CKD to end-stage renal disease are not yet clear, but, injury (AKI), formerly known as acute renal failure, in a large intuitively, we believe that such costs must be great. pediatric cohort. During a 10-year period, they found that During the last decade a revolution has occurred in the ap2.7% of patients developed NSAIDproach to AKI. Signicant advances have See related article, p  associated AKI as diagnosed by The Internaoccurred through our improved undertional Classication of Diseases, Ninth Revision, codes and standing of the epidemiology of AKI,6 standardization and stratied by the Pediatric Risk, Injury, Failure, Loss, End validation of a pediatric denition of AKIie, pRIFLE criteStage (pRIFLE) criteria.2 These numbers may have been ria,2 the discovery of a novel serum/urine AKI biomarker,7 greater. However, the authors rightfully censured their data and the validation and application and improvements in colby excluding patients with multifactorial etiologies of AKI laborative investigative efforts across multiple pediatric cenbeyond NSAID use. What was surprising was the nding ters.8 We are now realizing the long-term impact of AKI on that the majority of these patients developed AKI despite rethe development of CKD.6 The identication of important ceiving NSAID dosing determined on the basis of recommenAKI-associated variables in terms of morbidity and mortality ded guidelines. (ie, uid overload) and paradigm shifts in terms of AKI risk Given the widespread availability and use of NSAIDs in pestratication have also allowed us to view AKI a different diatrics,3 these ndings are sobering. Drug-induced renal inlight.9 4 jury is a well-recognized risk when prescribing medications. The population impact of AKI cannot be underestimated. Between 1996 and 2008 the number of hospitalizations assoMore often than not, antibiotics (ie, aminoglycosides) are ciated with any cause of AKI increased 4-fold.10 In terms of implicated in the development of AKI; however, the administration of intravenous forms of these types of medications morbidity and mortality, the individual patient impact of generally are restricted to hospital or specialty centerbased AKI is immense.11 Indeed the associated population health practices. Indeed NSAIDs often are used in the very same paimpact is also signicant. A wealth of data exists to suggest tients who receive aminoglycosides, without the prescribing that AKI leads to CKD in adults.12 Observational and small physician aware of the potential impact on renal function. studies also implicate this course in pediatric and neonatal So too is the case in infants and neonates, in whom renal depopulations.6 Despite these alarming data, there continues velopment may be negatively impacted by the use of potento be a relatively poor awareness of AKI, its risk factors, tially renal toxic medications early in life.5 and its short- and long-term consequences on individual and population health. Early recognition of any cause of Although a provider may recognize the individual patientAKI may therefore have a profound effect on short-term specic impact of an AKI diagnosis, the cost and population morbidity/mortality, length of hospital stay, and short-term impact often are overlooked. Misurac et al1 provide a consercosts. In the longer term, these cost savings could be imvative cost ($375 293 over 10 years) expenditure estimate in mense. the care of children with NSAID-associated AKI at their inImproving early provider recognition of drug-associated stitution. These costs excluded critical and surgical care comAKI in a busy hospital ward or ofce practice may seem ponents from patients who required dialysis and other a daunting and potentially expensive task; however, the ancillary services. Given that NSAID-associated AKI is an rapidly changing landscape of AKI health care delivery lends avoidable condition and that these patients occupied beds, itself to just this effort in a value-based, cost effective, potenthe real costs are amplied through increased length of tially cost-saving fashion. Several concomitant health care stay, with reduced payor reimbursement and loss of revenue developments make tackling drug-associated AKI a tantalizfrom unavailable beds. Seventy percent of patients with ing target. These include: (1) the generalized implementation NSAID-associated AKI (with available follow-up data) had of electronic health records (EHRs) across health care institua return of renal function to an estimated glomerular ltrations, which allow us to integrate AKI denitions (ie, pRIFLE tion rate (ie, Schwartz formula) of >90 mL/min/1.73 m2, sugcriteria) and create warning systems for age-appropriate gesting that 30% of patients in their cohort may have deviations from creatinine norms and pharmacy-based drug interaction warnings; (2) the paradigm-changing
AKI CKD EHR NSAID pRIFLE Acute kidney injury Chronic kidney disease Electronic health record Nonsteroidal anti-inammatory drug The Pediatric Risk, Injury, Failure, Loss, End Stage

The author declares no conicts of interest.

0022-3476/$ - see front matter. Copyright 2013 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2013.01.065

THE JOURNAL OF PEDIATRICS

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Table. Pediatric renal angina threshold
Hazard tranche Moderate-risk patients  Patients admitted to PICU

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conceptualization of renal angina13 as a clinical guide to assess patients at risk for AKI; (3) the universally recognized benets of reducing length of hospital stay and medical errors; and (4) the advancement of patient safety efforts and therefore value-based care. Although many providers bemoan the difculty in switching to electronically based health records, these records do provide some inherent advantages. The intended purpose for the EHR is to improve patient care and information portability while reducing paperwork for providers. However, many providers found these systems cumbersome and awkward to navigate. They have added to workload rather than improve care delivery. EHR vendors should be accountable to the organizations they serve and therefore providers must impress upon EHR vendors that they must be able to deliver the tools required to improve care. It is imperative that those who care for children demand that appropriate identication of abnormal renal indices, from the neonate to the young adult, are available for our patients. In addition, incorporating validated AKIdening criteria into the EHR (such as the pRIFLE) is necessary. Finally, by identifying patients receiving renal toxic medications and allowing pharmacy-based oversight of these warnings, we ought to be able to impact positively the rate of hospital-acquired AKI. Simply put, EHRs can be designed to do what we need them to do, but we must advocate for this design and hold vendors accountable. The conceptual framework of renal angina13 provides an easily implementable, low-cost, evolving clinical paradigm for bedside prediction of patients at risk for the development of AKI. Although much progress has been made in the development of novel AKI biomarkers with the goal of early identication of AKI, their diagnostic accuracy and predictive utility are limited by the lack of a consistent and reliable framework to guide appropriate use in patients.7 In the case of renal angina, a collection of clinical risk factors (ie, history of cardiopulmonary bypass, bone marrow transplantation, state of mechanical ventilation,) paired with evidence of renal injury (ie, serum creatinine changes, uid overload) allows the clinician to risk-stratify patients so that clinical investigations (including novel biomarkers) may be used to rule out AKI in at-risk patients. That is, the renal angina threshold = AKI risk AKI evidence (Table).14 Applying this concept to bedside care could improve patient outcomes. Pairing this concept with an EHR-based agging system for renal toxic medications and AKI recognition would certainly provide a low-cost intervention for a high cost disease. Most importantly, it could improve patient safety and health care value. Reducing medical errors, avoiding medication-induced injury, and reducing hospital length of stay go hand in hand with improving patient safety. These efforts truly provide a win-win scenario for our health care system in terms of cost reduction/improved efciency and improved value-based care. The growing presence of multidisciplinary institutional patient safety councils, chief
2

Renal angina threshold Doubling of SCr or eCrCl decrease >50% or ICU uid overload >15% SCr increase $0.3 mg/dL or eCrCl decrease 25%-50% or ICU uid overload >10% Any SCr increase or eCrCl decrease >25% or ICU uid overload >5%

High-risk patients  Acute decompensated heart failure  Stem-cell transplant recipient Very-high-risk patients  Receiving mechanical ventilation and one or more vasoactive medications

eCrCl, estimated creatinine clearance; ICU, intensive care unit; PICU, pediatric intensive care unit; SCr, serum creatinine. Adapted from Basu et al.14 Patients are stratied into moderate-risk, high-risk, and very-high-risk groups according to their underlying clinical condition. Each stratum is paired with a threshold of evidence of renal injury that a patient must meet to be considered to have renal angina. Patients with lower risk for AKI on the basis of their clinical history require greater evidence of renal injury to meet the criteria for renal angina.

medical ofcers, and medical/nursing director partnerships are emblematic of a changing health system. These are the agents that will foster a change in how we approach patient value-based care. n Patrick D. Brophy, MD, MHCDS University of Iowa Childrens Hospital University of Iowa Iowa City, Iowa
Reprint requests: Patrick D. Brophy, MD, Director, Pediatric Nephrology, Dialysis & Transplantation, University of Iowa Childrens Hospital, Carver College of Medicine, University of Iowa, 1269A-CBRB, 285 Newton Rd, Iowa City, IA 52242. E-mail: patrick-brophy@uiowa.edu

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9. Askenazi D. Evaluation and management of critically ill children with acute kidney injury. Curr Opin Pediatr 2011;23:201-7. 10. US Department of Health and Human services; National Kidney and Urologic Diseases Informational Clearinghouse website. http://kidney. niddk.nih.gov/kudiseases/pubs/kustats/#1. Accessed February 1, 2013. 11. Selby NM, Kolhe NV, McIntyre CW, Monaghan J, Lawson N, Elliott D, et al. Dening the cause of death in hospitalized patients with acute kidney injury. PLoS One 2012;7:e48580.

EDITORIAL
12. Leung KC, Tonelli M, James MT. Chronic kidney disease following acute kidney injury-risk and outcomes. Nat Rev Nephrol 2012;81: 442-8. 13. Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol 2010;5: 943-9. 14. Basu RK, Chawla LS, Wheeler DS, Goldstein SL. Renal angina: an emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol 2012;27:1067-78.