Evaluation of the Plasmatic NGAL as a Predictive Marker of Renal Injury in Children With Urinary Infection. (Perf-NGAL-IU) (Perf-NGAL-IU)

Evaluation of the Plasmatic and Urinary Neutrophil Gelatinase - Associated Lipocalin as a Predictive Marker of Renal Injury in Children With Febrile Urinary Infection

Urinary infections in children is very common. Delay in the diagnosis may be followed by complications.

Pyelonephritis is a febrile urinary infection with a renal injury. In local experience, about 30-40% of the children don't have an inflammatory syndrome or echographical abnormalities. Do they really have a renal injury ? In fact, only the scintigraphy or the Magnetic Resonance Imaging (MRI) may show these lesions, but are done only in specific cases (diagnosis of uropathy or nephropathy). Recent studies have shown that plasmatic Neutrophil Gelatinase-Associated Lipocalin (NGAL) is associated traumatic or inflammatory renal lesions. But the plasmatic NGAL cutoff is fluctuant depending on the cohorts and gold standards. The main goal is to evaluate a new methodology of dosing NGAL, (immuno-dosage turbidimetric dosage). The investigators suppose that plasmatic NGAL protein will detect renal injury, which would be confirmed by MRI.

The aim of this study is to evaluate the area under the curve (AUC) of plasmatic NGAL protein with an automatised method, for the detection of renal injury. This would be confirmed by reno vesical MRI, in children over 2 years old with febrile urinary infections

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infections
• Intervention / Treatment: Diagnostic test: plasmatic NGAl and MRI

Detailed Description

Urinary infections in children is very common and should be diagnosed as soon as possible. Delay in the diagnosis ma be followed by complications such as sepsis, renal scar, high blood pressure, renal insufficiency.

The diagnosis may be tough when it comes to children because of its unspecific symptomatology. Pyelonephritis is a febrile urinary infection associated to renal abnormalities. Following the french recommendations ("Sociéte de Pathologie Infectieuse de Langue Française" The French Society of Infectious disease SPILF and "Groupe de Pathologies Infectieuses Pédiatriques" The Pediatric infectious disease Group GPIP 2015), the investigators should first use an intravenous probabilistic antibiotic during minimum 48 hours to lower the bacterial inoculum. Then, the investigators should switch to an oral antibiotic during 8 days to sterilise the urines.

In local experience, about 30 to 40 % of the children don't have an inflammatory syndrom or echographical abnormalities. Do they really have a renal injury? In fact, only the scintigraphy or the Magnetic Resonance Imaging (MRI) may show these lesions, but are done only in specific cases (diagnosis of uropathy or nephropathy). Recent studies have shown that plasmatic Neutrophil Gelatinase-Associated Lipocalin (NGAL) is associated traumatic or inflammatory renal lesions. But the plasmatic NGAL cutoff is fluctuant depending on the cohorts and gold standards. In those studies, dosing NGAL was non automatised and long.

the investigators would like to evaluate a new methodology of dosing NGAL, (immuno-dosage turbidimetric dosage). The investigators suppose that plasmatic NGAL protein will detect renal injury, which would be confirmed by MRI.

This is an interventional, prospective, multicentered study. It will last for 2 years. The aim of this study is to evaluate the AUC of plasmatic NGAL protein with an automatised method, for the detection of renal injury. This would be confirmed by reno vesical MRI, in children over 2 years old with febrile urinary infections.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France
    • Fondation Lenval Hopitaux Pediatriques de Nice Chu Lenval

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children over 4 years old, continent
• Fever ≥ 38,5 degrés Celsius for less than 4 days
• Positive urine strip
• Parental authorisation
• Using french Health Care System

Exclusion Criteria:

• Uropathy
• 2nd febrile urinary infection
• No parental authorisation
• Non confirmed Urinary infection on a well done Cyto Bacteriological Urine (CBU)
• Urinal contamination defined by : ≥ 2 bacterial, urinal bacteriuria < 10^5 Colony Forming Unit (CFU)/ml

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: plasmatic NGAL and MRI	Diagnostic test: plasmatic NGAl and MRI; Determination of plasma NGAL protein during routine blood test Realization of a reno vesical MRI at 48 hours of inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare plasmatic Neutrophil Gelatinase-Associated Lipocalin (NGAL) with gold standard Reno vesical Magnetic Resonance Imaging (MRI)	NGAL will be evaluated in urines, and plasma. The method will be automatised. The dosage will be from 25 to 5000 ng/ml. Gold standard will be MRI (nephritis is defined by hyperintense zones in diffusion sequence and hyposignal in ADC mode) The primary outcome measure is to estimate the area under the curve (AUC) defining the different measures of the performance (Sensitivity, specificity) of plasmatic NGAL protein in ng/ml according to the presence or not of a kidney lesion diagnosed at the RMI (gold standard).	48 hours after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define performance of plasmatic NGAL for the diagnostic of renal abnormality due to a pyelonephritis	The performance of NGAL will be evaluated (sensitivity, specificity, positive predictive value, negative predictive value) using the chosen cutoff of NGAL. Gold standard will be reno vesical MRI	48 hours after inclusion
Performance and area under the curve (AUC) of C-reactive Protein (CRP) for the diagnostic of pyelonephritis	The performance (sensitivity, specificity, positive predictive value, negative predictive value) and the AUC of CRP will be defined using the following cutoff (CRP > 20 mg/l ) chosen from the litterature. CRP will be dosed by an automatised method on XL Siemens machine.	48 hours after inclusion
Performance and area under the curve (AUC) of Procalcitonin (PCT) for the diagnostic of pyelonephritis	The performance (sensitivity, specificity, positive predictive value, negative predictive value) and the AUC of PCT will be defined using the following cutoff ( PCT > 0,5 ng/ml) chosen from the litterature. PCT will be dosed using a Brahms automat	48 hours after inclusion
Compare the AUC of plasmatic NGAL and CRP	AUC for plasmatic NGAL will be compared to AUC of CRP, AUC will be calculated using receiver operator characteristic (ROC) curves	48 hours after inclusion
Compare the AUC of plasmatic NGAL and PCT.	AUC for plasmatic NGAL will be compared to AUC of PCT. AUC will be calculated using receiver operator characteristic (ROC) curves	48 hours after inclusion
Performance of urinary NGAL	Define an area under receiver operator characteristic (ROC) curve based on the dosage of urinary NGAL used to diagnose renal abnormality. The method will be automatised. The dosage will be from 25 to 5000 ng/ml. Gold standard will be MRI (nephritis is defined by hyperintense zones in diffusion sequence and hyposignal in Apparent Diffusion coefficient (ADC) mode).	48 hours after inclusion
Performance of doppler echography	The performance of doppler echography (sensitivity, specificity, positive predictive value, negative predictive value) will be established using MRI as a gold standard.	48 hours after inclusion

Collaborators and Investigators

• Sponsor: Fondation Lenval
• Investigators: Principal Investigator: Tran Antoine, MD, Children Hopital of Nice CHU-Lenval Emergency

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): October 26, 2023

Study Registration Dates

• First Submitted: August 27, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Communicable Diseases; Urinary Tract Infections
• Other Study ID Numbers: 18-HPNCL-08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No