Clinical trial NCT04344769: 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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autosomal Dominant Polycystic Kidney Disease
Keywords: Oxidative Stress
Antioxidant Response
Nrf2
ADPKD
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-04-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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).

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

Primary outcomes:
measure: Assessment of Oxidative Status
timeFrame: Baseline
measure: Assessment of Antioxidant Response
timeFrame: Baseline
measure: Total kidney volume (TKV)
timeFrame: Baseline
Secondary outcomes:
measure: Assessment of Kidney Injury
timeFrame: Baseline
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Translational PKD Center, Mayo Clinic
name: Maria V. Irazabal, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: