The PRO-FUTURE Project

Chronic Kidney Diseases Clinical Trial

— PRO-FUTURE  

Official title:

PRecocious biOmarkers oF Unilateral ureTero-pelvic jUnction obstRuction in childrEn

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06382233
• Other study ID #: PRO-FUTURE project
• Status: Recruiting
• Start date: January 30, 2024
• Est. completion date: January 30, 2028

Study information

• Verified date: April 2024
• Source: University of Campania "Luigi Vanvitelli"
• Contact: Pierluigi Marzuillo, MD PhD
• Phone: 00390815665344
• Email: pierluigi.marzuillo[@]unicampania.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 85
• Est. completion date: January 30, 2028
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 5 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hydronephrosis
• Kidney Diseases
• Multicystic Dysplastic Kidney
• Renal Insufficiency, Chronic
• Ureteral Obstruction
• Ureteropelvic Junction Obstruction

Intervention

Diagnostic Test:
• Identification of Diagnostic Biomarkers
Urinary single-cell and EVs screening to stage the intrarenal injury and repair processes in UPJO babies and identification of the whole blood gene expression profiling of babies with unilateral UPJO. Data deriving from patients with unilateral UPJO will be compared with data deriving from controls.

Locations

Country	Name	City	State
Italy	Department of Clinical Sciences and Community Health, University of Milano	Milan
Italy	Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico	Milan
Italy	Obstetrics and Gynecology Unit, University of Modena and Reggio Emilia	Modena
Italy	AORN Santobono-Pausilipon	Naples
Italy	Univeristà degli Studi della Campania Luigi Vanvitelli	Naples	Campania

Sponsors (5)

Lead Sponsor	Collaborator
University of Campania "Luigi Vanvitelli"	A.O.R.N. Santobono-Pausilipon, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, University of Modena and Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine Biomarkers	The investigators will focus on the urine by investigating for intrarenal remodeling processes and searching for kidney-specific biomarkers by urinary single-cell and EVs screening (aim 1).	48 months
Primary	Blood Biomarkers	Moreover, based on the hitherto revealed capability of blood cells to perceive organ-specific illnesses, the investigators will perform WBGEP of babies with unilateral UPJO to identify early biomarkers of disease progression (aim 2).	48 months