Autosomal Dominant Polycystic Kidney Disease
Conditions
Keywords
Oxidative Stress, Antioxidant Response, Nrf2, 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).
Interventions
None listed
Sponsors
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total kidney volume (TKV) | Baseline | Determined by MRI |
| Assessment of Oxidative Status | Baseline | Determination of common biomarkers of oxidative damage including but not limited to: 8-oxodeoxyguanosine, F2-isoprostanes, from urine and plasma samples |
| Assessment of Antioxidant Response | Baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Kidney Injury | Baseline | 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), |
Countries
United States
Contacts
CONTACTAhmed Abdelfattah
CONTACTMaria V Irazabal, M.D., Ph.D
PRINCIPAL_INVESTIGATORMaria V. Irazabal, M.D., Ph.D
Mayo Translational PKD Center, Mayo Clinic
Outcome results
None listed