Iohexol for Measuring Renal Function (HERO)

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.

Study Overview

• Status: Unknown
• Conditions: Acute Kidney Injury; Critically Ill Children
• Intervention / Treatment: Drug: Iohexol Inj 300 MG/ML

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.

• Study Type: Observational
• Enrollment (Anticipated): 105

Contacts and Locations

• Study Contact: Name: Nori JL Smeets, MD; Phone Number: 0031-24-3614214; Email: nori.smeets@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboudumc
    • Contact: Nori JL Smeets, MD; Phone Number: 0031-24-3614214; Email: nori.smeets@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

105 critically ill children admitted to the pediatric intensive care unit or neonatal intensive care unit from the Radboudumc with at least one failing organ.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
To explore the relationship of genetic variation with the development of AKI.	72 hours

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Saskia N De Wildt, MD PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): April 30, 2021
• Study Completion (Anticipated): April 30, 2021

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Iohexol; Glomerular Filtration Rate
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: NL68547.091.18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No