A Study to Evaluate Renal Fibrosis Using MRI Techniques

Quantitative Magnetization Transfer MRI for Evaluation of Renal Fibrosis

The purpose of this study is to evaluate whether or not an MRI technique (quantitative magnetization transfer or qMT) in narrowing human kidneys is feasible, reproducible, and predicts recovery.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Renovascular
• Intervention / Treatment: Device: qMT-MRI to detect fibrosis.

Detailed Description

Renal fibrosis is a final pathway and important biomarker of injury common to most forms of kidney disease. For example, in renal vascular disease (RVD) progressive renal fibrosis may induce kidney injury and hypertension. Early identification of fibrosis and adequate intervention may slow down renal disease progression, but adequate noninvasive strategies to detect and quantify renal fibrosis are yet to be identified.

Magnetization transfer imaging (MTI) magnetic resonance imaging (MRI) is a novel noninvasive method to evaluate the tissue macromolecular composition. The investigators have demonstrated that MTI can assess stenotic kidney fibrosis in murine and swine models of unilateral RVD. However, the clinical utility of MT-MRI to assess renal fibrosis is currently limited, because it is inherently semi-quantitative. In contrast, quantitative MT (qMT), based on biophysical compartment models, provides more objective measurement of tissue MT properties. A model fitting of MR signal acquired with various MT pulse amplitudes and offset frequencies, combined with scan-specific B0/B1/T1 maps, give rise to a more complete definition of tissue parameters, including a "bound pool fraction", a direct measure of the macromolecular content in tissue.

The hypothesis underlying this proposal is that qMT would reliably detect development of renal fibrosis at both 1.5 T and 3.0 T in subjects with RVD. To test this hypothesis, which is supported by strong preliminary data, the investigators will initially develop, optimize, and validate qMT for evaluation of fibrosis in the post-stenotic swine kidney. The investigators will correlate qMT-derived renal fibrosis with reference standards, as well as with single-kidney hemodynamics, function, and oxygenation, quantified using cutting-edge multi-detector CT (MDCT) and MRI techniques. The investigators will then determine the ability of qMT to predict renal recovery in pigs with RVD undergoing revascularization. Further, they will perform a pilot study to test the ability of qMT to quantify fibrosis in the post-stenotic human kidney, in comparison to innovative biomarkers of renal dysfunction and tissue damage.

Three specific aims will test the hypotheses: Specific Aim 1: qMT in stenotic swine kidneys is feasible, reliable, and reproducible at 1.5 and 3.0 T. Specific Aim 2: qMT predicts renal recovery potential in response to percutaneous transluminal renal angioplasty (PTRA). Specific Aim 3: qMT in stenotic human kidneys is feasible, reproducible, and predicts recovery.

The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to quantify kidney fibrosis, a key biomarker for renal outcomes and therapeutic success.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Steph DiRenzo; Phone Number: 507-422-2044; Email: DiRenzo.Stephany@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Between ages 40 and 80 years old.
• Patients with hypertension (BP>140/90 mmHg) and/or requirement for two or more antihypertensive medications for more than 4 weeks.
• Serum creatinine under 2.2 and 2.0 mg/dL for men and women, respectively (Caucasians). Values for African-American subjects are slightly higher (2.4 mg/dL, males; 2.1 mg/dL females).
• No contraindications to angiography: severe contrast allergy.
• No contraindications to no-contrast MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia.
• Patients have the ability to comply with protocol
• Patients are competent and able to provide written informed consent

Exclusion Criteria:

• Patient has serum creatinine >2.2 mg/dL for men and >2.0 mg/dL for women (Caucasians); >2.4 mg/dL for men and >2.1 mg/dL for women (African American).
• RVD in a solitary kidney
• Patients have clinically significant medical conditions within the prior six months: e.g. myocardial infarction, congestive heart failure, stroke, that would, in the opinion of the investigators, compromise the safety of the patient.
• Uncontrolled hypertension (Systolic BP >180 mmHg despite therapy).
• Diabetes requiring insulin or oral hypoglycemic medications.
• Evidence of hepatitis B or C, or HIV infection.
• Requirement for potentially nephrotoxic drugs; e.g., non-steroidal anti-inflammatory drugs.
• Cardiac ejection fraction less than 30%.
• History of deep venous thrombosis within 3 months of enrollment.
• Kidney transplant.
• Pacemaker, implantable defibrillator or other contraindication to MRI
• Inability to comply with breath-hold for 20 seconds
• Any active malignancy and undergoing therapy
• Patients are pregnant.
• Kidney or ureteric stone
• Another known acute or chronic kidney disease
• Federal medical center inmates.
• Latex allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Early identification of fibrosis.; A pilot study to test the ability of qMT to quantify fibrosis in the post-stenotic human kidney, in comparison to innovative biomarkers of renal dysfunction and tissue damage. We will pursue the Specific Aim that qMT in stenotic human kidneys is feasible and reproducible.	Device: qMT-MRI to detect fibrosis.; The hypothesis underlying this proposal is that qMT would reliably detect development of renal fibrosis at both 1.5T and 3.0T in subjects with RVD. Patients will be studied with MRI (for fibrosis) and CT (for renal function).; Other Names: CT scanning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis assessed by qMT-MRI in the stenotic kidney and contralateral kidneys	A significant difference in qMT bound pool fraction (f, %) in the stenotic compared to the contralateral kidney in RVD patients.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis assessed by qMT-MRI compared to stenotic kidney function	A significant correlation between qMT bound pool fraction (f, %) with function (SK-GFR) and oxygenation (SK-R2*) in the stenotic kidney.	Baseline
Fibrosis assessed by qMT-MRI compared to stenotic kidney injury markers	A significant correlation between qMT bound pool fraction (f, %) with levels of renal injury markers: Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecular (KIM)-1, lactate dehydrogenase (LDH)], as well as urinary levels of extracellular vehicles (EVs) (measured by flow cytometry, %) originating from renal microvessels.	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Lilach O Lerman, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 8, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis
• Other Study ID Numbers: 19-008413; R01DK122734 (U.S. NIH Grant/Contract)

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