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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DK128017-01 | 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 assess homocysteine metabolism and systemic endothelial function at the early stages of the disease and determine the prognostic value of homocysteine, related metabolites, and markers of endothelial function and injury to estimate renal disease severity and progression in patients with early Autosomal Dominant Polycystic Kidney Disease (ADPKD).
ADPKD is a devastating systemic disorder characterized by progressive development and enlargement of bilateral renal cysts, often leading to renal failure. Disease severity and progression vary widely among patients. Large phenotypic variability, incomplete understanding of underlying mechanisms, and lack of suitable biomarkers challenge potential therapies' identification, implementation, and evaluation.
In ADPKD, systemic endothelial dysfunction (ED), characterized by an imbalance between vasodilating (particularly nitric oxide, NO) and vasoconstricting substances, develops early and correlates with renal disease severity. It has been previously associated with decreased NO availability, but NO abnormalities' mechanisms are still poorly understood. Endothelium-dependent, NO-mediated vasodilation is impaired in subjects with hyperhomocysteinemia, suggesting that NO availability is decreased in these subjects. Increased plasma levels of homocysteine have been reported in patients with ADPKD and preserved kidney function, likely contributing to a reduction in NO bioavailability. The mechanisms underlying increased homocysteine in ADPKD are not known. Furthermore, whether systemic endothelial function and injury or homocysteine levels can predict renal disease severity and progression in patients is unknown.
The investigators' broad objective is to assess homocysteine metabolism and systemic endothelial function at the early stages of the disease and determine the prognostic value of homocysteine, related metabolites, and markers of endothelial function and injury to estimate renal disease severity and progression in patients with early ADPKD.
Participants in this study will have a blood and a urine sample collected to determine biomarkers of oxidative stress, endothelial function and injury, homocysteine, and related metabolite levels. In addition, peripheral arterial tonometry (PAT) will determine systemic endothelial function, and an abdominal MRI will be performed to determine the 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in height adjusted Total kidney volume (htTKV) | TKV determined by MRI | Baseline to 24 months |
| Baseline endothelial function, homocysteine and related metabolite levels as predictors of change in TKV | Endothelial function determined by PAT and biochemical markers, TKV determined by MRI | Baseline to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in systemic endothelial function | Endothelial function determined by PAT | Baseline to 24 months |
| Change in biochemical markers related to endothelial function and injury | Determined by ELISA and/or biochemical assays |
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Inclusion Criteria:
Exclusion Criteria:
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Male and female patients with a previous diagnosis of ADPKD that meet the inclusion criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Maria V Irazabal, M.D.;Ph.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Study information | 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
| Baseline to 24 months |
| Change in homocysteine and related metabolite levels | Determined by 1HNMR, Mass spect, ELISA | Baseline to 24 months |
| Change in Renal blood flow (RBF) | Determined by MRI | Baseline to 24 months |
| Change in estimated Glomerular filtration rate (GFR) | eGFR determined by CKD-epi equation | Baseline to 24 months |
| NADPH oxidase 4 (NOX4) expression/activity | Determined by ELISA | Baseline to 24 months |
| 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 |