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| ID | Type | Description | Link |
|---|---|---|---|
| R21DK118391 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| 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 |
| 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 |
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Inclusion Criteria (ADPKD Subjects):
Exclusion Criteria (ADPKD Subjects):
Inclusion Criteria (Healthy Subjects):
Exclusion Criteria (Healthy Subjects):
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ahmed Abdelfattah | Contact | Abdelfattah.Ahmed@mayo.edu | ||
| Maria V Irazabal, M.D., Ph.D | Contact | 507-884-5628 | irazabalmira.maria@mayo.edu |
| Name | Affiliation | Role |
|---|---|---|
| Maria V. Irazabal, M.D., Ph.D | Mayo Translational PKD Center, Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Recruiting | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| ID | Term |
|---|---|
| D007690 | Polycystic Kidney Diseases |
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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Urine and plasma samples
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |