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| Name | Class |
|---|---|
| University of Kansas Medical Center | OTHER |
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The purpose of this study is to determine whether patients with autosomal dominant polycystic kidney disease (ADPKD) present with abnormal endothelial function, increased levels of NOX4 activity and mitochondrial abnormalities, contributing to oxidative stress from early stages that correlate with disease severity.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic and the fourth cause of end-stage renal disease (ESRD) in adults worldwide. Cardiovascular diseases are the most important non-cystic complications and continue to be the leading cause of premature mortality in these patients. Hypertension (HTN) is present in approximately 50% of the patients at early stages, and increases to nearly 100% at ESRD. Furthermore, HTN contributes to the underlying renal disease progression. Nitric oxide (NO) associated endothelium-dependent vasorelaxation has been shown to be impaired in small subcutaneous resistance vessels from patients with ADPKD before the development of HTN. However, the principal contributors to vascular dysfunction remain unclear.
The investigators broad objective is to evaluate the presence and extent of endothelial dysfunction and its association with oxidative stress in young normotensive patients with ADPKD, with the long term goal of timely intervention to slow the progression of the disease in these patients.
Participants in this study will have their endothelial function assessed using a non-invasive technique, peripheral arterial tonometry (PAT), which has been shown to be a useful, highly reproducible, and non-operator dependent method for non-invasive assessment of vascular health. The investigators will assess longitudinal changes in endothelial function using PAT with the intention of establishing if this methodology offers the potential of non-invasive measures of early vascular disease in young normotensive patients with ADPKD. Biochemical markers of endothelial dysfunction will be assessed concomitantly. In addition, the investigators will assess oxidative stress levels in these patients, with the intention of determining the association with endothelial dysfunction.
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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 endothelial function by Peripheral Artery Tonometry (PAT) | PAT is a novel non-invasive technology which records volume changes in the microcirculation of the digits in response to hyperemia, to measure peripheral vasodilator response as a measure for endothelial dysfunction. | 18 months |
| NADPH oxidase 4 (NOX4) expression/activity | Determined by ELISA from plasma and urine | 18 months |
| Mitochondrial DNA copy number | Plasma and urine levels of the mitochondria encoded genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-1 (ND1) determined by quantitative real-time polymerase chain reaction | 18 months |
| Total kidney volume (TKV) | Determined by MRI | 18 months |
| Renal blood flow (RBF) | Determined by MRI | 18 months |
| Glomerular filtration rate (GFR) | Determination of iothalamate clearance | 18 months |
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Inclusion Criteria:
ADPKD Patients:
Healthy controls:
Exclusion Criteria:
ADPKD Patients:
Healthy controls:
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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 2:1 to age and gender healthy controls. Exclusion criteria are listed in for ADPKD patients and healthy controls.
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| 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 | 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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| 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 |