Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) (Search_CAKUT)

Non-invasive Evaluation of Kidneys in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Using Ultrasound Localization Microscopy

This clinical study aims to non-invasively visualize perfusion and microvascularization, as well as individual glomeruli, using Ultrasound Localization Microscopy (ULM) and CEUS in patients with congenital anomalies of the kidney and urinary tract (CAKUT).

Study Overview

• Status: Recruiting
• Conditions: Congenital Anomalies of Kidney and Urinary Tract; Ureteropelvic Junction Obstruction; Lower Urinary Tract Obstruction, Congenital; Hydronephrosis Congenital
• Intervention / Treatment: Device: Contrast enhanced ultrasound imaging (CEUS) and post processing with ULM

Detailed Description

Congenital anomalies of the kidney and urinary tract (CAKUT) affect 0.5% of newborns and account for 20% of all congenital malformations. These conditions are associated with chronic kidney failure, a need for dialysis, and significantly increased mortality (30 times higher than healthy peers) and morbidity. Patients with CAKUT face substantial health and socioeconomic burdens due to lifelong therapy requirements. In Europe, CAKUT is the leading cause of dialysis-dependent chronic kidney failure.

All CAKUT disorders arise in utero, interfering with kidney development and leading to reduced nephron formation. Many congenital kidney anomalies are diagnosed via prenatal ultrasound. These anomalies include ureteropelvic junction obstruction, often presenting as unilateral hydronephrosis, and posterior urethral valves, which can be associated with megacystis and bilateral hydronephrosis. The resulting urinary obstruction can cause pressure damage to kidney tissue during fetal development, further reducing functional nephron mass. Postnatally, ongoing pressure damage can lead to renal remodeling. The decreased nephron mass and remodeling increase the long-term risk of kidney insufficiency, which is currently assessed only by serum creatinine levels-these are delayed and less sensitive in infants and young children. Reliable biomarkers for reduced nephron mass or renal remodeling to predict chronic kidney injury risk in CAKUT patients are currently lacking. Currently, the actual pressure impact of sonographically detectable urinary obstruction can only be assessed through urine flow patterns using MAG-3 scintigraphy. However, this method is dependent on kidney function, which can affect the uptake and excretion of the radiopharmaceutical and subsequently influence the evaluation of results.

The intravenous use of ultrasound contrast enhancers as an aid opens up the possibility of recording the tissue perfusion of the kidneys, including the smallest vessels, independent of the kidney function. This could provide significantly more information compared to conventional methods and expand our knowledge of the pathophysiology and individual status of tissue perfusion in patients.

In this clinical study, the new CEUS measurement and imaging technique will be used after the kidney scintigraphy. A contrast agent (SonoVue®) will be administered during the routine ultrasound examination and improved tissue visualization will be achieved. The aim is to gain new insights into kidney perfusion as part of the treatment and to better assess the extent of organ damage in the individual patient through more specific vascular imaging. Finally, the aim is to compare diagnostic and prognostic methods with the currently recommended measures. The CEUS is to be examined as a possible diagnostic imaging tool and possibly a supplement to existing diagnostic methods.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Regensburger Regensburger, PD Dr. med. Dr. rer. biol. Hum; Phone Number: 091318541732; Email: adrian.regensburger@uk-erlangen.de
• Study Contact Backup: Name: Dr. med. Alina Hilger; Email: alina.hilger@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • FAU Erlangen-Nuernberg,
      • Contact: Dr. med. Alina Hilger; Email: alina.hilger@uk-erlangen.de
      • Contact: PD Dr. med. Dr. rer. biol. Hum. Adrian Regensburger; Email: adrian.regensburger@uk-erlangen.de

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

One study population. Anticipated approx. n=20 children with above mentioned inclusion criteria with congenital anomalies of the kidney and urinary tract and inclusion criteria for MAG3 scintigraphy

Description

Inclusion Criteria:

Minimum Age 1 Month Maximum Age 6 Years Indication for MAG3 Scintigraphy of the Kidney Congenital Anomalies of the Kidney and Urinary Tract Obstruction Diagnosis Availability of the qualified examiner Consent of the parents/legal guardians

Exclusion Criteria:

Lack of consent of at least one parent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with congenital anomalies of the kidney and urinary tract (CAKUT) with indication for MAG3; Included will be children under the age of 6 with congenital anomalies of the kidney and urinary tract (CAKUT)that get an indication for a MAG3 scintigraphy. They will be monitored with CEUS/ULM after the MAG3 scintigraphy.	Device: Contrast enhanced ultrasound imaging (CEUS) and post processing with ULM; CEUS is a contrast based ultrasound technique and ULM (Ultrasound Localization Microscopy) is a post-processing bioinformatical method to quantify microvascular architecture and perfusion dynamics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CEUS Measurement1	PE (Peak-Enhancement)	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Time intensity curves	All CEUS outcomes will be generated in order to achieve time intensity curves in contrast enhanced ultrasound analysis	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement2	WiAUC (Wash-in Area Under the Curve (AUC(TI: TTP)))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement4	RT (Rise Time)	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement5	mTT (mean Transit Time local) (mTT-TI))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement6	TTP (Time to Peak)	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement7	WiR (Wash-in-Rate )	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement8	WiPI (Wash-in Perfusion Index (WiAUC/RT))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement9	WoAUC (Wash-out AUC (AUC(TTP:TO)))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement10	WiWoAUC (Wash-in- und Wash-out-AUC (WiAUC+WoAUC))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement11	FT (Fall Time - (TO-TTP))	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement12	WOR (Wash-out-Rate) QOF (Quality Of Fit between the echo-power signal and f(t)	Baseline and follow up (1-31 days after routine surgery if indicated)
CEUS Measurement13	QOF (Quality Of Fit between the echo-power signal and f(t)	Baseline and follow up (1-31 days after routine surgery if indicated)
Visualization and quantification of kidney perfusion with CEUS	CEUS imaging for kidney perfusion in CAKUT	Baseline and follow up (1-31 days after routine surgery if indicated)
Visualization and quantification of kidney mikrovaskularisation with ULM	ULM imaging for kidney perfusion and mikrovaskularisation in CAKUT	Baseline and follow up (1-31 days after routine surgery if indicated)
Visualization and quantification of glomeruli in the kidney with ULM	ULM imaging for glomeruli in the kidney	Baseline and follow up (1-31 days after routine surgery if indicated)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ULM and Ultrasound	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with sonographic parameters (including Resistance Index (RI), flow velocity).	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM and CEUS	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with parameters of contrast-enhanced ultrasound (CEUS).	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM and Biopsy	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (including the number of segmented glomeruli) with histological parameters.	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM on affected and unaffected kidney	Comparison of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) between the affected and unaffected kidney in the same patient.	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM and Scintigraphy	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with parameters from renal scintigraphy (e.g., perfusion parameters).	Baseline and follow up (1-31 days after routine surgery if indicated)
Pressure changes with CEUS	Visualization of pressure changes in the kidney using the vascular architecture visualized by CEUS and parameters of quantified microvascular perfusion dynamics.	Baseline and follow up (1-31 days after routine surgery if indicated)
Pressure changes with ULM	Visualization of pressure changes in the kidney using the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics.	Baseline and follow up (1-31 days after routine surgery if indicated)
Comparison of the kidney before and after intervention with ULM	Comparison of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) before and after intervention	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM on different diagnoses	Comparison of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) between different diagnoses.	Baseline and follow up (1-31 days after routine surgery if indicated)
ULM on clinical outcomes	Correlation and comparison of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with clinical criteria and clinical outcomes (surgical success).	Baseline and follow up (1-31 days after routine surgery if indicated)
Correlation between ULM and laboratory parameters	Correlation of the vascular architecture visualized by ULM and parameters of quantified microvascular perfusion dynamics of the kidney (e.g., number of segmented glomeruli) with laboratory parameters (including kidney function parameters, inflammatory markers, and immunological parameters).	Baseline and follow up (1-31 days after routine surgery if indicated)
Assessment of renal function GFR	GFR (ml/min/1,73 m2)	Baseline and follow up (1-31 days after routine surgery if indicated)
Assessment of renal function urea	urea (mg/dl)	Baseline and follow up (1-31 days after routine surgery if indicated)
Assessment of renal function urinary status	standardized urinary status	Baseline and follow up (1-31 days after routine surgery if indicated)
Assesment of renal function kreatininekinase	kreatininekinase (U/l)	Baseline and follow up (1-31 days after routine surgery if indicated)

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 21, 2024
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Cakut; Multicystic renal dysplasia, bilateral
• Other Study ID Numbers: Search_CAKUT_ULM

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
• product manufactured in and exported from the U.S.: No