Clinical trial NCT06382233: The PRO-FUTURE Project
Official title: PRecocious biOmarkers oF Unilateral ureTero-pelvic jUnction obstRuction in childrEn
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ureteropelvic Junction Obstruction
Chronic Kidney Diseases
Keywords: Ureteropelvic junction obstruction
Biomarkers
Single-Cell
Extracellular vesicles
Congenital anomalies of the kidney and urinary tract
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
Collaborators: name: University of Milan
name: A.O.R.N. Santobono-Pausilipon
name: University of Modena and Reggio Emilia
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
First posted: 2024-04-24
Enrollment: 85
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Definition of cases (patients with UPJO): in this project, the investigators define the UPJO as an hydronephrosis needing of surgical correction on the basis of at least 2 of the following criteria: APDP ≥ 30 mm, SRF less than 40% at the Mag3S, SRF with delta \> 10% at follow-up Mag3S compared with the first Mag3S, delayed wash-out following diuretic administration, progressive increase of the APDP at follow-up kidney ultrasounds, 4th degree hydronephrosis. Otherwise, the hydronephrosis will be defined as non-obstructive.

Definition of controls: babies aged 0-5 years and needing of surgical correction for hernia, hydrocele or phimosis.

Brief summary: The goal of this observational study is to learn about specific biomarkers of unilateral ureteropelvic junction obstruction (UPJO) in children undergoing surgical intervention for unilateral UPJO compared with controls. The main question it aims to answer are:

* Are Urinary single-cell and extracellular vesicles (EVs) screening useful to stage the intrarenal injury and repair processes in UPJO babies?
* Do babies with unilateral UPJO have a whole blood gene expression profiling (WBGEP) allowing an accurate unilateral UPJO diagnosis?

Detailed description: Congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of chronic kidney disease in children. UPJO is the most common CAKUT. It is defined as impeded urine outflow from the renal pelvis to the ureter, which may result in progressive kidney damage (KD). Renal imaging is the current diagnostic approach, even if substantial shortcomings are present to reliably determine a significant obstruction. Consequently, a follow up is often needed with the risk of progressive KD. The main hypothesis of this proposal is that biofluids (whole blood and urine) could allow a more precise diagnosis and risk stratification of unilateral UPJO compared with the available diagnostic techniques.

In this project the investigators define the UPJO as an hydronephrosis needing of surgical correction according to 2 of the following criteria: anterior-posterior diameter of the pelvis (APDP) ≥ 30 mm, split renal function (SRF) \< 40% at the Tc99mMag3 scintigraphy (Mag3S), SRF with delta \> 10% at follow-up Mag3S, delayed wash-out, progressive increase of the APDP at follow-up ultrasounds, and 4th degree hydronephrosis.

The investigators will extensively investigate for specific biomarkers of UPJO at different levels. The investigators will focus 1. on the urine by investigating for intrarenal remodeling processes and searching for kidney-specific biomarkers by urinary single-cell and EVs screening (aim 1). Moreover, based on the hitherto revealed capability of blood cells to perceive organ-specific illnesses, 2. the investigators will perform WBGEP of babies with unilateral UPJO to identify early biomarkers of disease progression (aim 2).

For the aims 1 and 2, the investigators will enroll 85 patients aged 0-5 years, 35 with unilateral UPJO and 50 controls without hydronephrosis needing surgical correction for hernia, hydrocele or phimosis.

This project could improve the management of patients with suspect of UPJO -starting from birth- by a better understanding of the pathophysiological mechanisms underlying KD and by the identification of early biomarkers of obstruction, reducing the costs and the complications related to either a tardive or not needed surgical correction and reducing the risk of KD development.

Eligibility criteria: Inclusion Criteria:

* unilateral UPJO
* 0-5years of age

Exclusion Criteria:

* bilateral UPJO
* previous surgical intervention on the urinary tract
* bladder or lower urinary tract symptoms or malformations
* nephro- or urolithiasis, vesicoureteral reflux
* urinary tract infections.

Primary outcomes:
measure: Urine Biomarkers
timeFrame: 48 months
measure: Blood Biomarkers
timeFrame: 48 months
Secondary outcomes:
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Univeristà degli Studi della Campania Luigi Vanvitelli
state: Campania
city: Milan
country: Italy
facility: Department of Clinical Sciences and Community Health, University of Milano
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Obstetrics and Gynecology Unit, University of Modena and Reggio Emilia
city: Naples
country: Italy
facility: AORN Santobono-Pausilipon
Study officials:
References: