The PRO-FUTURE Project (PRO-FUTURE)

PRecocious biOmarkers oF Unilateral ureTero-pelvic jUnction obstRuction in childrEn

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?

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Ureteropelvic Junction Obstruction
• Intervention / Treatment: Diagnostic test: Identification of Diagnostic Biomarkers

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.

• Study Type: Observational
• Enrollment (Estimated): 85

Contacts and Locations

• Study Contact: Name: Pierluigi Marzuillo, MD PhD; Phone Number: 00390815665344; Email: pierluigi.marzuillo@unicampania.it

Study Locations

• Italy
  • Milan, Italy
    • Active, not recruiting
    • Department of Clinical Sciences and Community Health, University of Milano
  • Milan, Italy
    • Recruiting
    • Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico
    • Principal Investigator: Giovanni Montini
    • Contact: Giovanni Montini
    • Principal Investigator: Alfredo Berrettini
    • Sub-Investigator: Michele Gnech
  • Modena, Italy
    • Recruiting
    • Obstetrics and Gynecology Unit, University of Modena and Reggio Emilia
    • Contact: Giovanni Grandi
    • Principal Investigator: Giovanni Grandi
    • Sub-Investigator: Stefano Puliatti
  • Naples, Italy
    • Recruiting
    • AORN Santobono-Pausilipon
    • Contact: Giovanni Di Iorio
    • Principal Investigator: Giovanni Di Iorio
    • Sub-Investigator: Agnese Roberti
  • Campania
    • Naples, Campania, Italy, 80138
      • Recruiting
      • Univeristà degli Studi della Campania Luigi Vanvitelli
      • Contact: Pierluigi Marzuillo
      • Principal Investigator: Pierluigi Marzuillo
      • Principal Investigator: Paolo Montaldo
      • Principal Investigator: Carmine Noviello
      • Sub-Investigator: Alfonso Papparella
      • Sub-Investigator: Stefano Guarino
      • Sub-Investigator: Anna Di Sessa
      • Sub-Investigator: Grazia Cirillo
      • Sub-Investigator: Giusy Capasso

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Babies with unilateral UPJO; Children aged 0-5 years with unilateral UPJO. Unilateral UPJO will be defined 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.	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.
Controls of babies with unilateral UPJO; Children aged 0-5 years needing of surgical correction for hernia, hydrocele, phimosis or cryptorchidism.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: April 19, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; Extracellular vesicles; Congenital anomalies of the kidney and urinary tract; Ureteropelvic junction obstruction; Single-Cell
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Urogenital Abnormalities; Congenital Abnormalities; Renal Insufficiency; Ureteral Diseases; Kidney Diseases, Cystic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Ureteral Obstruction; Multicystic Dysplastic Kidney; Hydronephrosis
• Other Study ID Numbers: PRO-FUTURE project

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