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

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Brief Title

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

Official Title

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

Brief Summary

      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.
    

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


Primary Outcome

Assessment of Oxidative Status

Secondary Outcome

 Assessment of Kidney Injury

Condition

Autosomal Dominant Polycystic Kidney Disease


Study Arms / Comparison Groups

 Patients with a previous diagnosis of ADPKD
Description:  Patients that have been diagnosed with ADPKD and meet the study's inclusion criteria

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

40

Start Date

October 4, 2019

Completion Date

March 31, 2022

Primary Completion Date

September 30, 2021

Eligibility Criteria

        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
      

Gender

All

Ages

18 Years - 30 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Maria V. Irazabal, MD, (507) 266-1316, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04344769

Organization ID

17-008806

Secondary IDs

R21DK118391

Responsible Party

Principal Investigator

Study Sponsor

Mayo Clinic

Collaborators

 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Sponsor

Maria V. Irazabal, MD, Principal Investigator, Mayo Translational PKD Center, Mayo Clinic


Verification Date

May 2021