Intrarenal Microvasculature in ADPKD

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

Official title:

Noninvasive Evaluation of the Intrarenal Microvasculature in ADPKD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05288998
• Other study ID #: 21-005117
• Secondary ID: 1R21DK129886-01
• Status: Recruiting
• Start date: November 30, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Mayo Clinic
• Contact: Ahmed Abdelfattah
• Phone: 507-284-2908
• Email: Abdelfattah.Ahmed[@]mayo.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria (Patients with ADPKD):

• Male and female subjects 18 - 40 years of age, inclusive

• Previous diagnosis of ADPKD (based on Ravine et al. criteria)

• Class 1 according to imaging classification

• Estimated GFR> 70 mL/min/m2 (CKD-Epi equation)

• Ability to provide written, informed consent

Inclusion Criteria (Healthy Volunteers):

• Male and female subjects 18 - 40 years of age, inclusive

• Estimated GFR> 90 mL/min/m2 (CKD-Epi equation)

• Ability to provide written, informed consent

Exclusion Criteria (Patients with ADPKD):

• Class 2 according to imaging classification

• A concomitant systemic disease affecting the kidney (e.g., lupus, hepatitis B or C, amyloidosis)

• Diabetes mellitus (fasting glucose > 126 mg/dL or treatment with insulin or oral hypoglycemics).

• Predicted urine protein excretion in urinalysis >1 g/24 hrs.

• Subjects having contraindications to or interference with MRI assessments. [For example ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc.].

• History of hypersensitivity allergic reactions to ultrasound contrast agents

• High-risk cardiac disease (such as unstable hospital in-patients or ICU patients

• Patients that are part of an interventional study or are taking tolvaptan

• Female subjects that are pregnant

Exclusion Criteria (Healthy Volunteers):

• Family and/or personal history of kidney disease

• Concomitant systemic disease that may affect the kidney

• Diabetes mellitus

• Predicted urine protein excretion in >1 g/24 hrs, and or Abnormal urinalysis

• Pregnant or lactating women

• Subjects having contraindications to or interference with MRI assessments. [For example ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc.].

• History of hypersensitivity allergic reactions to ultrasound contrast agents

• High risk cardiac disease (such as unstable hospital in-patients or ICU patients

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of intrarenal microvascular density in HV and patients with ADPKD	Renal vessel density as percentage, determined by SRU.	Baseline
Primary	Assessment of intrarenal microvascular flow speed in HV and patients with ADPKD	Microvascular flow speed (mm/s), determined by SRU.	Baseline
Primary	Assessment of intrarenal microvascular perfusion in HV and patients with ADPKD	Intrarenal perfusion (mm/s), determined by SRU.	Baseline
Primary	Assessment of intrarenal tortuosity indices in HV and patients with ADPKD	Tortuosity indices defined as sum of angles metric (SOAM) (rad/mm), determined by SRU	Baseline
Secondary	Inter-sonographer variability of the intrarenal microvasculature	Second US at the same visit performed by a different sonographer, and used to calculate the intraclass correlation coefficient	Baseline
Secondary	Day-to-day variability of intrarenal microvasculature in healthy volunteers	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	Baseline to 7 days
Secondary	Patient-to-patient variability in patients with ADPKD	Correlation between primary outcome measures and image class (A, B, C, D and E) as determined by the Image classification.	Baseline