Impact of Pediatric Acute Renal Injury in Severe Sepsis in Young Adults

Withdrawn

• Conditions: Chronic Kidney Disease; Acute Kidney Injury; Hypertension
• Interventions: Drug: Iodohippurate; Procedure: 24 hour ambulatory Blood Pressure; Procedure: Peripheral Arterial Tonometry; Procedure: Pulse Wave Velocity; Drug: Gadolinium

• Registration Number: NCT02599844
• Lead Sponsor: University of Florida

Brief Summary

Sepsis is the most common cause of childhood death worldwide. Millions of children survive, but are left with impaired health. Sepsis-related Acute Kidney Injury (sAKI) is increasingly recognized as a significant factor associated with long-term mortality among different patient populations. Renal dysfunction and subsequent chronic kidney disease is implicated in the development of hypertension and cardiovascular disease. The investigators overall hypothesis is that, in the pediatric population, sepsis-related AKI will have unrecognized, long-term consequences with regard to kidney function, endothelial function, blood pressure control, and overall health.

Detailed Description

This will be a two-arm cross-sectional control-cohort outpatient evaluation. Subjects with sAKI and a random selection of non-sAKI subjects who agree to participate in another study of quality of life survey will be asked to participate in the outpatient study. Subjects will be asked to come in to the Clinical Research Center for 24-hour monitoring and participate in the outpatient study where urinary and serum studies to measure glomerular filtration rate, renal plasma flow followed by blood pressure monitoring, peripheral arterial and applanation tonometry.

Study Timeline

• Study First Submitted: 2015-11-02
• Study First Submitted QC: 2015-11-04
• Study First Posted: 2015-11-09
• Study Start: 2015-12
• Primary Completion: 2020-02-01
• Study Completion: 2020-02-01
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-26
• Last Update Posted: 2020-03-27

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

For all patients:

• Age 18-24 at time of participation in the study

For non-AKI sepsis patients:

• Hospitalization with a diagnosis of sepsis from 1998-2014
• Failure to meet pEDRIFLE criteria for AKI during incident sepsis admission
• Participation in cognitive survey study with completion of the PedsQL survey

For sAKI patients:

• Hospitalization with a diagnosis of sepsis from 1998-2014
• Severe AKI as defined by the pEDRIFLE criteria during incident sepsis admission
• Participation in cognitive survey study with completion of the PedsQL survey

Exclusion Criteria

For all patients:

• Known pre-existing CKD as defined by history of kidney transplant or long-term dialysis
• Age greater than 18 years at the time of incident sepsis admission
• AKI from primary kidney disease including acute glomerulonephritis and obstructive uropathy
• Pregnancy at the time of enrollment
• Known or suspected allergy to gadolinium based contrast
• Known or suspected allergy to iodine or shellfish will be excluded from RPF measurement with iodohippurate
• Heart failure or condition whereby the administration of 0.9% normal saline would be contraindicated

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sepsis with Severe AKI	Gadolinium	This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis without AKI	Gadolinium	This group will have a history of a pediatric admission with sepsis which lead to no classification of sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis with Severe AKI	Peripheral Arterial Tonometry	This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis with Severe AKI	24 hour ambulatory Blood Pressure	This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis with Severe AKI	Pulse Wave Velocity	This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis without AKI	Peripheral Arterial Tonometry	This group will have a history of a pediatric admission with sepsis which lead to no classification of sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis without AKI	Pulse Wave Velocity	This group will have a history of a pediatric admission with sepsis which lead to no classification of sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis without AKI	24 hour ambulatory Blood Pressure	This group will have a history of a pediatric admission with sepsis which lead to no classification of sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis with Severe AKI	Iodohippurate	This group will have a history of pediatric admission with sepsis-related Acute Kidney Injury (sAKI) which lead to classification of "injury" or "failure". The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).
Sepsis without AKI	Iodohippurate	This group will have a history of a pediatric admission with sepsis which lead to no classification of sepsis-related Acute Kidney Injury (sAKI). The following test will be performed: urinary and serum studies to measure glomerular filtration rate by using gadolinium, renal plasma flow by using an injection of non-radioactive iodohippurate, followed by cardiovascular assessments using 24 hour ambulatory blood pressure monitoring, peripheral arterial tonometry and pulse wave velocities (PWV).

Primary Outcome Measures

Name	Time	Method
Glomerular Function Rate (GFR) filtration	Day 2	Magnevist Gadolinium (GD)-diethylene-triamine-pentaacetic acid-bis-oleate (0.07 to 0.14 mL/kg) will be used to determine GFR.
Renal plasma flow (RPF) filtration	Day 2	An injection of non-radioactive iodohippurate (0.07 mL/kg) will be administered to determine renal plasma flow (RPF) filtration.
Proteinuria will be measured in the urine	Day 2	Proteinuria may be a sign of renal (kidney) damage. Since serum proteins are readily reabsorbed from urine, the presence of excess protein indicates either an insufficiency of absorption or impaired filtration. People with diabetes may have damaged nephrons and develop proteinuria.
Cystatin C will be measured in the blood	Day 2	Cystatin C can be measured in a random sample of serum (the fluid in blood from which the red blood cells and clotting factors have been removed) using immunoassays such as nephelometry or particle-enhanced turbidimetry.
Microalbuminuria will be measured in the urine	Day 2	The level of albumin protein produced by microalbuminuria can be detected by special albumin-specific urine dipsticks. A microalbumin urine test determines the presence of the albumin in urine. In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys.

Secondary Outcome Measures

Name	Time	Method
Peripheral Arterial Tonometry	24 hours	The peripheral arterial tonometry (PAT) device measures changes in the cutaneous circulation that correlate with flow-mediated dilatation.
24 hour ambulatory Blood Pressure	24 hours	Ambulatory blood pressure (BP) monitoring will be performed using a commercially available device (TIBA Ambulo 2400) for 24 hours with measurements every 30 minutes while awake and every hour during sleep.
Pulse Wave Velocity	24 hours	Carotid-femoral and carotid-radial pulse wave velocities (PWV), validated markers of individual cardiovascular risk, will be determined by applanation tonometry using SphygmoCorVx technology (AtCor Medical). PWV is an index of the overall stiffness of a vascular segment between measurement sites 59. Thus, while carotid-femoral PWV is an index of the overall stiffness of proximal (central) arteries, the overall stiffness of peripheral arteries contributes relatively more to carotid-radial PWV.