Dataset Information

Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

ABSTRACT: OBJECTIVE:To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. METHODS:Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study. RESULTS:41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage. CONCLUSIONS:a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury.

SUBMITTER: Santiago MJ

PROVIDER: S-EPMC4752347 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

Santiago Maria José MJ Fernández Sarah Nicole SN Lázaro Alberto A González Rafael R Urbano Javier J López Jorge J Solana Maria José MJ Toledo Blanca B Del Castillo Jimena J Tejedor Alberto A López-Herce Jesús J

PloS one 20160212 2

<h4>Objective</h4>To design an experimental pediatric animal model of acute kidney injury induced by cisplatin.<h4>Methods</h4>Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were c ...[more]

PMID: 26871589

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Project description:INTRODUCTION:Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS:A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS:A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS:Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

Project description:BackgroundAcute kidney injury (AKI) in pediatric critical care patients is diagnosed using elevated serum creatinine, which occurs only after kidney impairment. There are no treatments other than supportive care for AKI once it has developed, so it is important to identify patients at risk to prevent injury. This study develops a machine learning model to learn pre-disease patterns of physiological measurements and predict pediatric AKI up to 48 h earlier than the currently established diagnostic guidelines.MethodsEHR data from 16,863 pediatric critical care patients between 1 month to 21 years of age from three independent institutions were used to develop a single machine learning model for early prediction of creatinine-based AKI using intelligently engineered predictors, such as creatinine rate of change, to automatically assess real-time AKI risk. The primary outcome is prediction of moderate to severe AKI (Stage 2/3), and secondary outcomes are prediction of any AKI (Stage 1/2/3) and requirement of renal replacement therapy (RRT). Predictions generate alerts allowing fast assessment and reduction of AKI risk, such as: "patient has 90% risk of developing AKI in the next 48 h" along with contextual information and suggested response such as "patient on aminoglycosides, suggest check level and review dose and indication".ResultsThe model was successful in predicting Stage 2/3 AKI prior to detection by conventional criteria with a median lead-time of 30 h at AUROC of 0.89. The model predicted 70% of subsequent RRT episodes, 58% of Stage 2/3 episodes, and 41% of any AKI episodes. The ratio of false to true alerts of any AKI episodes was approximately one-to-one (PPV 47%). Among patients predicted, 79% received potentially nephrotoxic medication after being identified by the model but before development of AKI.ConclusionsAs the first multi-center validated AKI prediction model for all pediatric critical care patients, the machine learning model described in this study accurately predicts moderate to severe AKI up to 48 h in advance of AKI onset. The model may improve outcome of pediatric AKI by providing early alerting and actionable feedback, potentially preventing or reducing AKI by implementing early measures such as medication adjustment.

Dataset Information

Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

Publications

Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

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