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

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.

• ULM and Ultrasound [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM and CEUS [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM and Biopsy [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM on affected and unaffected kidney [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM and Scintigraphy [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• Pressure changes with CEUS [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• Pressure changes with ULM [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• Comparison of the kidney before and after intervention with ULM [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM on different diagnoses [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• ULM on clinical outcomes [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• Correlation between ULM and laboratory parameters [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]
• Assessment of renal function GFR [Time frame: Baseline and follow up (1-31 days after routine surgery if indicated)]