Intrarenal Microvasculature in ADPKD

Recruiting

• Conditions: Autosomal Dominant Polycystic Kidney Disease

• Registration Number: NCT05288998
• Lead Sponsor: Mayo Clinic

Brief Summary

The primary objective of this study is to evaluate the use of Super-resolution ultrasound (SRU) to assess the intrarenal microvasculature in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and healthy volunteers.

Detailed Description

An intact intrarenal microcirculation is vital to preserving normal kidney function, and microvascular dysfunction, damage, and loss are known to contribute to renal function decline. In ADPKD, extensive vascular remodeling has been proposed to play an important role in its progression. However, microvascular analyses in rodents and humans with ADPKD have been performed ex vivo or in vitro and from kidneys removed at the time of renal failure due to the invasive nature and additional limitations of the currently available techniques. A non-invasive and direct method to assess the intrarenal microvasculature is needed to improve early detection and gauge the progression of microvascular alterations and monitor the success of therapeutic approaches.

Current imaging modalities, such as micro-computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound, have attempted to provide a non-invasive assessment of the intrarenal microvasculature in pre-clinical models of kidney diseases. However, each of these modalities has important limitations when translating into humans, including high cost, requiring long imaging times, using nephrotoxic contrast agents, radiation exposure, low spatial resolution, and poor reproducibility.

Super-resolution ultrasound (SRU) imaging is among the most rapidly advancing imaging techniques introduced to overcome the limitation of the inherent spatial resolution of ultrasound. With the use of non-nephrotoxic contrast microbubbles to break the diffraction limit of ultrasound, and the introduction of ultrasound localization microscopy which utilizes ultrafast frame rate imaging to reconstruct a super-resolved composite image, SRU has provided a paradigm-shifting tool for structural and functional evaluation of tissue microvasculature. However, in vivo, human imaging, and kidney imaging pose significant organ depth challenges (which results in ultrasound signals with lower signal-to-noise ratio) and physiologic and operator-induced motion (which reduces the available data accumulation time). Our team recently implemented advanced filtering and microbubble localization and tracking techniques to overcome these limitations, which extract only microbubble signals and reliably pinpoint the center of each microbubble from the extracted signals.

The investigators' broad objective is to deploy and evaluate the use of SRU imaging coupled with advanced post-processing techniques to assess the intrarenal microvasculature in patients with early ADPKD and healthy volunteers.

Participants in this study will have a renal ultrasound to determine intrarenal microvascular parameters, and an abdominal MRI to determine the patient's total kidney volume (TKV), and additional vascular parameters. In addition, participants will have a blood and a urine sample collected to determine biomarkers of endothelial function and injury.

Study Timeline

• Study Start: 2021-11-30
• Study First Submitted: 2022-02-21
• Study First Submitted QC: 2022-03-11
• Study First Posted: 2022-03-21
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-30
• Primary Completion: 2024-12
• Study Completion: 2025-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assessment of intrarenal microvascular density in HV and patients with ADPKD	Baseline	Renal vessel density as percentage, determined by SRU.
Assessment of intrarenal microvascular flow speed in HV and patients with ADPKD	Baseline	Microvascular flow speed (mm/s), determined by SRU.
Assessment of intrarenal microvascular perfusion in HV and patients with ADPKD	Baseline	Intrarenal perfusion (mm/s), determined by SRU.
Assessment of intrarenal tortuosity indices in HV and patients with ADPKD	Baseline	Tortuosity indices defined as sum of angles metric (SOAM) (rad/mm), determined by SRU

Secondary Outcome Measures

Name	Time	Method
Day-to-day variability of intrarenal microvasculature in healthy volunteers	Baseline to 7 days	A second US within 1-7 days is performed by the same sonographer, to determine the within-person variability for each of the primary outcome measures
Inter-sonographer variability of the intrarenal microvasculature	Baseline	Second US at the same visit performed by a different sonographer, and used to calculate the intraclass correlation coefficient
Patient-to-patient variability in patients with ADPKD	Baseline	Correlation between primary outcome measures and image class (A, B, C, D and E) as determined by the Image classification.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States