Iohexol for Measuring Renal Function

Study Overview
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Brief Summary
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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.

Detailed Description
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Primary objective: To determine the prevalence of AKI in critically ill children based on clearance of iohexol. Secondary objectives: 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. To determine serum Proenkephalin (PENK) levels in critically ill children. 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 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.

Official Title
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Iohexol for Measuring Renal Function

Conditions
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Acute Kidney Injury, Critically Ill Children

Intervention / Treatment
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* Drug: Iohexol Inj 300 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 0-18 years of postnatal age >37 weeks of gestational age (for infants < one year postnatal age) Bodyweight >2500g Patients admitted to pediatric or neonatal intensive care unit PELOD-II (pediatric logistic organ dysfunction score, 2nd version) of 1 or higher (= at least one failing organ) Indwelling central line or arterial line in place for clinical purposes, or scheduled regular blood work for clinical reasons (at least once a day) Informed written consent Exclusion Criteria: Known medical history of allergic reaction to injection of iodinated contrast material Receiving renal replacement therapy Language or cognitive inability of parents/caregivers to understand written and oral informed consent.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Iohexol Inj 300 MG/ML|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|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence 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. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 72 hours | 
| Serum PENK levels, in relation to iohexol based GFR-measurements in critically ill children. |  | 72 hours | 
| Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum creatinine levels |  | 72 hours | 
| Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on creatinine clearance |  | 72 hours | 
| Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum cystatin C levels |  | 72 hours | 
| Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum PENK levels |  | 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) |  | 72 hours | 
| Risk factors for the development of AKI when based on iohexol clearance. |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iohexol, Glomerular Filtration Rate