Iohexol for Measuring Renal Function

• Conditions: Acute Kidney Injury; Critically Ill Children

• Registration Number: NCT03946345
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2019-05
• Study Start: 2019-05-01
• Study First Submitted: 2019-05-03
• Study First Submitted QC: 2019-05-09
• Last Update Submitted: 2019-05-09
• Study First Posted: 2019-05-10
• Last Update Posted: 2019-05-10
• Primary Completion: 2021-04-30
• Study Completion: 2021-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

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

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Prevalence of AKI in critically ill children based on iohexol plasma clearance	72 hours	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.

Secondary Outcome Measures

Name	Time	Method
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
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on serum cystatin C levels	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.	72 hours	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.
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 serum PENK levels	72 hours
Agreement between diagnosis of AKI when based on iohexol clearance compared to diagnosis based on creatinine clearance	72 hours
Risk factors for the development of AKI when based on iohexol clearance.	72 hours

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands