Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With ADPKD

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

Official title:

Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) - A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03493802
• Other study ID #: 17-005944
• Status: Completed
• Start date: November 1, 2017
• Est. completion date: January 17, 2020

Study information

• Verified date: August 2022
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 17, 2020
• Est. primary completion date: January 17, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

ADPKD Patients:

• ADPKD (based on Ravine et al. criteria)
• Class 1 B-D according to our imaging classification
• Male and female subjects 18 - 40 years of age, inclusive
• Estimated GFR> 60 mL/min/m2 (CKD-Epi equation)
• Systolic BP=130mmHg without taking HTN medications
• Ability to provide written, informed consent

Healthy controls:

• Male and female subjects 18 - 40 years of age, inclusive
• estimated GFR> 60 mL/min/m2 (CKD-EPI equation)
• Systolic BP=130mmHg without taking HTN medications
• Ability to provide written, informed consent Exclusion Criteria:

ADPKD Patients:

• 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

Healthy controls:

• Previous personal or family history of kidney disease
• 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).
• Presence of proteinuria
• Abnormal urinalysis suggestive 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

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	University of Kansas Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	NADPH oxidase 4 (NOX4) expression/activity	Determined by ELISA from plasma and urine	18 months
Primary	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
Primary	Total kidney volume (TKV)	Determined by MRI	18 months
Primary	Renal blood flow (RBF)	Determined by MRI	18 months
Primary	Glomerular filtration rate (GFR)	Determination of iothalamate clearance	18 months

External Links

•   Mayo Clinic Clinical Trials