Characterization of the Nrf2 Response in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

The purpose of this study is to characterize oxidative stress and the Nrf2 antioxidant response in early stages of Autosomal Dominant Polycystic Kidney Disease (ADPKD), while identifying candidate biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Polycystic Kidney Disease

Detailed Description

Intracellular Reactive Oxygen Species (ROS) concentration is a major determinant of cellular fate and is finely regulated by the cell's antioxidant systems. While low levels of ROS are required for pro-survival signaling, cell proliferation, growth, and energy metabolism, the excess of ROS or oxidative stress leads to inflammation, cell death, and disease/injury progression. Indeed, oxidative stress is commonly observed in several renal diseases including ADPKD. On the other hand, a surplus of antioxidants will not only neutralize ROS, but may result in the antithesis of oxidative stress, which is known as reductive stress. The Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that integrates cellular stress signals and responds by regulating the expression of several antioxidant proteins. Activation of the Nrf2-mediated antioxidant defense pathway enhances ROS detoxification, conferring a more reduced intracellular environment that can promote cell survival and proliferation, a distinctive feature in ADPKD that underlies cyst formation and enlargement. Therefore, a better characterization of ROS levels and antioxidant response in ADPKD patients would allow development of more specific and effective therapies, while providing additional related biomarkers.

The investigators broad objective is to characterize oxidative stress and the Nrf2 antioxidant response in early stages of ADPKD, while identifying candidate biomarkers.

Participants in this study will have a blood and a urine sample collected to determine biomarkers of oxidative status and antioxidant response to study redox balance at early stages of the disease. In addition, an abdominal MRI will be performed to determine patient's total kidney volume (TKV).

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Ahmed Abdelfattah; Email: Abdelfattah.Ahmed@mayo.edu
• Study Contact Backup: Name: Maria V Irazabal, M.D., Ph.D; Phone Number: 507-884-5628; Email: irazabalmira.maria@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: 14 years to 26 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Male and female patients with a previous diagnosis of ADPKD that meet the inclusion criteria. In addition, patients will be matched 1:1 to age and gender healthy volunteers.

Description

Inclusion Criteria (ADPKD Subjects):

• ADPKD (based on Ravine et al. criteria)
• Class 1 B-E according to our imaging classification
• Male and female subjects 18 - 30 years of age, inclusive
• Estimated GFR> 60 mL/min/m2 (CKD-EPI equation)
• Ability to provide written, informed consent.

Exclusion Criteria (ADPKD Subjects):

• Class 2 according to our imaging classification
• Concomitant systemic disease in 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
• Abnormal urinalysis suggestive of concomitant glomerular disease.
• Subjects having contraindications to, or interference with MRI assessments. [For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc].
• Female subjects that are pregnant

Inclusion Criteria (Healthy Subjects):

• Male and female subjects 18 - 30 years of age, inclusive
• Estimated GFR> 60 mL/min/m2 (CKD-EPI equation)
• Ability to provide written, informed consent.

Exclusion Criteria (Healthy Subjects):

• Previous personal or family history of kidney disease.
• Concomitant systemic disease in the kidney (e.g. lupus, hepatitis B or C, amyloidosis)
• Diabetes mellitus (fasting glucose > 126 mg/dL or treatment with insulin or oral hypoglycemics).
• Presence of proteinuria
• Abnormal urinalysis suggestive glomerular disease.
• Subjects having contraindications to, or interference with MRI assessments. [For example: ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, large abdominal/back tattoos, etc]
• Female subjects that are pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with a previous diagnosis of ADPKD; Patients that have been diagnosed with ADPKD and meet the study's inclusion criteria
Healthy individuals as controls; Age and gender-matched healthy controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Oxidative Status	Determination of common biomarkers of oxidative damage including but not limited to: 8-oxodeoxyguanosine, F2-isoprostanes, from urine and plasma samples	Baseline
Assessment of Antioxidant Response	Determination of antioxidants including but not limited to: Heme Oxygenase 1 (HO-1), Superoxide dismutase (SOD), catalase, glutathione reductase (GSR), glutathione peroxidase (GPx), and NAD(P)H dehydrogenase [quinone] 1 (NOQ1), glutathione, Nrf2 from urine and plasma samples	Baseline
Total kidney volume (TKV)	Determined by MRI	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Kidney Injury	Determination of kidney injury biomarkers including but not limited to: Kidney Injury Molecule 1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Monocyte chemotactic protein-1 (MCP-1), Transforming growth factor-β1 (TGF-β1),	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Maria V. Irazabal, M.D., Ph.D, Mayo Translational PKD Center, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 10, 2020
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Oxidative Stress; ADPKD; Nrf2; Antioxidant Response
• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Polycystic Kidney Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Polycystic Kidney, Autosomal Dominant
• Other Study ID Numbers: 17-008806; R21DK118391 (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: No