Approximately 25-35% of all children admitted to the paediatric intensive care unit (PICU) or neonatal intensive care unit (NICU) will develop Acute Kidney Injury (AKI) during the first seven days after admission. AKI is associated with a worse outcome, including an increased risk of mortality compared to patients without AKI. However, this AKI prevalence estimation is based on serum creatinine based glomerular filtration rate (eGFR), which is known to be inaccurate. The investigators postulate that measured GFR (mGFR) based on iohexol clearance in critically ill children will detect a higher prevalence of children with AKI than currently used methods based on endogenous markers. This study will additionally provide mechanistic knowledge on the relative contribution of GFR and renal transport to renal function in critically ill children.
Primary objective: To determine the prevalence of AKI in critically ill children based on clearance of iohexol. Secondary objectives: 1. To determine the prevalence of AKI in critically ill children using serum creatinine, creatinine clearance, cystatin C and/or blood urea nitrogen based eGFR equations as well as urinary iohexol clearances. 2. To determine serum Proenkephalin (PENK) levels in critically ill children. 3. To compare the prevalence of AKI when this diagnosis is based on plasma iohexol clearances with the prevalence of AKI based on serum creatinine, creatinine clearance, serum cystatin C, PENK and/or Blood Urea Nitrogen (BUN) based eGFR and to assess agreement between those methods 4. To determine risk factors for the development of AKI when based on iohexol clearance. Exploratory endpoint: To explore the relationship of genetic variation with the development of AKI.
Study Type
OBSERVATIONAL
Enrollment
105
* Administration of iohexol: each 24 hours one bolus IV (1-5ml) during 72 hours * Blood samples are drawn for analysis of iohexol concentrations and other parameters of renal function at 2, 5 and 7 hours after administration * Urine is collected from catheter between 4 and 6 hours after adminstration to determine urine creatinine and iohexol concentrations
Radboudumc
Nijmegen, Netherlands
RECRUITINGPrevalence of AKI in critically ill children based on iohexol plasma clearance
AKI will be defined by using age-specific reference values of GFR. Based on their standard deviations (SD), three groups are defined: * Stage 1: mean -1 SD \> GFR \< mean -1.5 SD * Stage 2: mean -1.5 SD\> GFR \< mean -2 SD * Stage 3: GFR \< mean -2 SD Patients will be grouped according whether they lack AKI or have AKI (either stage 1, 2 or 3). When a patient will be classified as having AKI at one moment and not fulfilling the AKI-criteria at another, or classified into different stages of AKI within one day, the highest stage of the 72 hours will be used for analysis.
Time frame: 72 hours
Prevalence of AKI using serum creatinine, creatinine clearance, urinary iohexol, serum cystatin C, serum PENK and/or blood urea nitrogen based eGFR equations.
Classification of AKI based on serum creatinine levels: * Stage 1: serum creatinine concentration \>150% of median age specific reference value. * Stage 2: serum creatinine concentration \>200% of median age specific reference value. * Stage 3: serum creatinine concentration \>300% of median age specific reference value. Creatinine clearance: CrCl(ml/min/1.73m2) = (urine volume × urine creatinine × 1.73)/ (serum creatinine × 120 minutes × body surface area) AKI classification based on serum cystatin C levels will be similar to classification based on serum creatinine levels Urinary iohexol clearance: Ku(X)(t)=dXu/dt \& Cl(u)=dXudt/AUCpdt AKI will be classified based on eGFR calculated by the CKiD Schwartz Equation Data will be analysed for the overall 72 hour period, using the highest grade of AKI during the study duration, as well as per 24 hour period.
Time frame: 72 hours
Serum PENK levels, in relation to iohexol based GFR-measurements in critically ill children.
Time frame: 72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum creatinine levels
Time frame: 72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on creatinine clearance
Time frame: 72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum cystatin C levels
Time frame: 72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum PENK levels
Time frame: 72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on CKiD Schwartz Equation (Serum Creatinine, BUN and Cytatin C)
Time frame: 72 hours
Risk factors for the development of AKI when based on iohexol clearance.
Time frame: 72 hours
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