Role of Homocysteine Metabolism, Endothelial Function and Microvascular Rarefaction on Renal Disease Severity and Progression in ADPKD
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Mayo Clinic
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in height adjusted Total kidney volume (htTKV)
研究概览
简要总结
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).
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 15 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and Female subjects, 15-40 years of age, inclusive
- •Previous diagnosis of ADPKD (Based on Ravine et al. criteria)
- •Class 1 according to imaging classification
- •Estimated GFR>70 mL/min/1.73m^2(CKD-EPI)
- •Ability to provide written, informed consent.
排除标准
- •Class 2 according to imaging classification
- •A concomitant systemic disease affecting the kidney
- •Diabetes mellitus
- •Predicted urine protein excretion in urinalysis >1 g/24 hrs
- •Subjects having contraindications to or interference with MRI assessments
- •Patients that are part of an interventional study or taking tolvaptan
- •Female subjects that are pregnant
研究组 & 干预措施
Patients with a previous diagnosis of ADPKD
Patients that have been diagnosed with ADPKD and meet the study's inclusion criteria
结局指标
主要结局
Change in height adjusted Total kidney volume (htTKV)
时间窗: Baseline to 24 months
TKV determined by MRI
Baseline endothelial function, homocysteine and related metabolite levels as predictors of change in TKV
时间窗: Baseline to 24 months
Endothelial function determined by PAT and biochemical markers, TKV determined by MRI
次要结局
- NADPH oxidase 4 (NOX4) expression/activity(Baseline to 24 months)
- Change in Renal blood flow (RBF)(Baseline to 24 months)
- Change in homocysteine and related metabolite levels(Baseline to 24 months)
- Change in biochemical markers related to endothelial function and injury(Baseline to 24 months)
- Change in systemic endothelial function(Baseline to 24 months)
- Change in estimated Glomerular filtration rate (GFR)(Baseline to 24 months)
研究者
Maria V. Irazabal Mira
Principal Investigator
Mayo Clinic