Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study.
ABSTRACT Aminoglycosides (AG) cause acute kidney injury (AKI), but the incidence and severity distribution are unclear, particularly in non-critically ill children. We determined the incidence, severity and risk factors of AG-associated AKI and assessed for associations with longer hospitalization and higher costs.
At Texas Children's Hospital, we conducted a retrospective cohort study of children treated with AG for ≥ 5 days in 2005, excluding children with admission primary renal diagnoses. AKI was defined by the paediatric Risk, Injury, Failure, Loss, End Stage Kidney Disease (pRIFLE) and Acute Kidney Injury Network (AKIN) definitions. Multiple logistic and linear regression analyses were used to assess independence of associations with outcomes.
Five hundred and fifty-seven children [mean ± SD age = 8.0 ± 5.9 years, 286 (51%) male, 489 (88%) gentamicin] were studied. The AKI rate was 33% and 20% by pRIFLE and AKIN definitions, respectively. Longer treatment, higher baseline estimated glomerular filtration rate, being on a medicine (versus surgical) treatment service and prior AG treatment were independent risk factors for AKI development. AKI by pRIFLE or AKIN was independently associated with longer hospital stay and higher total hospital costs. The pRIFLE definition was more sensitive for AKI detection, but the AKIN definition was more strongly related to outcomes.
AKI is common and associated with poorer outcomes in non-critically ill children treated with AG. Future research should attempt to understand how to best define AKI in the non-critical illness paediatric setting.
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ABSTRACT: Acute kidney injury is a serious problem occurring in anywhere between 8 and 30% of children in the intensive care unit. Up to 25% of these cases are believed to be the result of pharmacotherapy. In this review we have focused on several relevant drugs and/or drug classes, which are known to cause AKI in children, including cancer chemotherapeutics, non-steroidal anti-inflammatory drugs, and antimicrobials. AKI demonstrates a steady association with increased long-term risk of poor outcomes including chronic kidney disease and death as determined by the extent of injury. For this reason it is important to understand the causality and implications of these drugs and drug classes. Children occupy a unique patient population, advocating for the importance of understanding how they are affected dissimilarly compared with adults. While the kidney itself is likely more susceptible to injury than other organs, the inherent toxicity of these drugs also plays a major role in the resulting AKI. Mechanisms involved in the toxicity of these drugs include oxidative damage, hypersensitivity reactions, altered hemodynamics and tubule obstruction and may affect the glomerulus and/or the tubules. Understanding these mechanisms is critical in determining the most effective strategies for treatment and/or prevention, whether these strategies are less toxic versions of the same drugs or add-on agents to mitigate the toxic effect of the existing therapy.British Journal of Clinical Pharmacology 11/2014; DOI:10.1111/bcp.12554 · 3.69 Impact Factor
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ABSTRACT: Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations. Observational, electronic medical record-enabled study of 14,795 hospitalizations at the Lucile Packard Children's Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov-Smirnov tests, respectively. AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%-1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%. Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition. Copyright © 2015 by the American Society of Nephrology.Clinical Journal of the American Society of Nephrology 02/2015; 10(4). DOI:10.2215/CJN.01900214 · 5.25 Impact Factor
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ABSTRACT: The use of antimicrobial agents has increased in recent years as treatments have diversified and resistant bacteria have appeared. With increased use of antimicrobial agents, elderly patients are prone to adverse drug reactions (ADRs) as a result of factors such as drug-drug interactions, polypharmacy, long-term use, and over- or under-dosage. In particular, elderly patients using antimicrobials are at increased risk to develop drug-induced acute kidney injury (AKI), which is the most common severe ADR in such patients. AKI is a serious problem that is associated with mortality amongst hospitalized patients. Antimicrobial-induced AKI can be classified into three different types: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), and renal tubule lumen obstruction. AKI can generally be prevented by proper maintenance of fluid balance. To design dosage regimens that ensure efficient drug excretion via the kidney, it is necessary to accurately estimate renal function; however, the kidney undergoes age-dependent structural and functional alterations over time. Therefore, proper management of antimicrobial agents by an antimicrobial stewardship team may lead to decreased incidence of AKI. This article reviews antimicrobial-induced AKI and discusses potential strategies for increasing awareness of AKI and mitigating its clinical effects.Drugs & Aging 12/2014; 32(1). DOI:10.1007/s40266-014-0232-y · 2.50 Impact Factor