When the Kidney Reacts to Nutritional Changes

NCT ID: NCT04142138

Last Updated: 2021-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-22
• Study Completion Date: 2021-04-30

Brief Summary

Hypertension is one of the leading causes of morbidity and mortality in the industrialized world, attributed mostly to modifiable lifestyle factors. Aspects that are controlled by patients include physical activity, smoking, alcohol consumption, and nutrition. The DASH (Dietary Approach to Stop Hypertension) diet is a proven effective intervention in lowering blood pressure in multiple populations. In this proof of concept study, volunteers with untreated stage 1 hypertension, defined as mild high blood pressure with numbers in the range of 130 - 139 over 80 - 89, will receive a DASH-based menu during 5 days of hospitalization, during a weekend at home where they will continue the menu, another 5 days as inpatients, followed by a weekend at home on the same menu, and the return to the inpatient unit for an additional day for final testing. Throughout the intervention period, participants will be followed clinically and undergo repeated laboratory testing. The aim of this project is to characterize changes in urine electrolytes and exosome protein abundance pattern during nutritional changes, shifting from a "westernized diet" to a DASH diet.

Detailed Description

Diet is a major disease modifier of hypertension. The Dietary Approaches to Stop Hypertension diet (DASH) is endorsed nationally and abroad to treat hypertension (HTN) in adults. In the original DASH study, the effect of the combination diet consisting of low salt, high potassium, and low-fat dairy products, was more pronounced in hypertensives and minorities. The magnitude of the effect on blood pressure (BP) of the combination diet was similar to that observed with single drug antihypertensive therapy.

Americans typically consume 3400 mg sodium daily, due to high intakes of processed foods, frequent eating outside the home, and consumption of packaged meals and salty snack foods. Foods consumed outside of the home provide 34% of the sodium intake of Americans.

It is not known exactly how the DASH diet effects its lowering of blood pressure. One of the proposed mechanism of the effect of the DASH diet relies on two components - sodium reduction and potassium supplementation.

In response to potassium supplementation such as in DASH diet, we would expect less sodium to be reabsorbed.

Over the years, adherence to DASH diet has been evaluated using questionnaires. Methods for monitoring sodium intake remain inadequate and flawed. Dietary recall is not reliable, and many patients truly do not realize, and consequently under report, the amount of sodium they consume. The most widely employed method of assessing dietary adherence, the 24-h urine collection to measure sodium excretion, is cumbersome and inconvenient. Evaluating urine sodium to creatinine ratio was validated as a surrogate measure to 24-hour urine collection .

Exosomes: most of the data regarding tissue activity of different channels in response to stimuli, comes from animal studies. Translation of the murine experimental findings to a human setting is difficult and has mostly been inferred using plasma and urinary electrolyte levels as a proxy for renal tubular transporter activity. Transporter proteins from all tubular segments are excreted into the urine in extracellular vesicles. These vesicles therefore provide a non-invasive liquid biopsy access to tubular epithelial cells that could potentially inform on physiological regulation of transporter activity in human kidneys . The proteins that are present in urine are a major area of investigation for proteomics researchers. In normal urine, typically half of the proteins are soluble proteins (49%), and the remaining 48% are sediment precipitated with low-speed centrifugation, and exosomes (3%). All exosomes contain a few common protein components. The cytosolic proteins present on exosomes include annexins, adhesion molecules, proteins that participate in vesicle formation and trafficking and metabolic enzymes. Analysis of urine exosomes can enhance the detectability of relatively low-abundant proteins that have potential pathophysiological significance, and so have become one of the newer trends in the field of urine-biomarker discovery .

Volunteers with hypertension stage 1, but otherwise healthy, will complete a screening visit, then be admitted to the In-Patient Unit for fourteen (14) days. Participants will be admitted for 5 days during the week and then go on pass for 2 weekend days each week with packed DASH diet meals. During hospitalization blood and urine samples will be collected daily, as well as clinical parameters such as blood pressure.

Conditions

Prehypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

nutrition implementation

Volunteers with prehypertension, but otherwise healthy, will complete a screening visit, then be admitted to the In-Patient Unit for fourteen (14) days. Participants will be admitted for 5 days during the week and then go on pass for 2 weekend days each week with packed DASH diet meals. During hospitalization we will: 1) collect samples of blood and urine daily 2) monitor blood pressure, weight and pulse twice daily 3) collect 24-hour urine, twice during the period of two weeks 4) serve participants a menu based on DASH principles, namely low in sodium and high in potassium.

Group Type: EXPERIMENTAL

DASH

Intervention Type: OTHER

DASH diet is based on low salt, high potassium components, and is comprised of mainly fruits and vegetables. During hospitalization we will collect laboratory data of blood and urine, and follow participants clinically by measuring blood pressure.

Interventions

DASH

DASH diet is based on low salt, high potassium components, and is comprised of mainly fruits and vegetables. During hospitalization we will collect laboratory data of blood and urine, and follow participants clinically by measuring blood pressure.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. any gender, 18-60 years of age

2. self described as White or Black individuals

3. prehypertensives (=stage 1 hypertension) defined as sustolic blood pressure of 130-159 mmHG and/or diastolic blood pressure between 80-100.

4. adequate dentition to consume fruits and vegetables as described for DASH -

Exclusion Criteria

1. Preexisting kidney disease structural or parenchymal including APCKD (adult polycystic kidney disease), single kidney (as assessed by ultrasound including size differences >3 cm in diameter between kidneys), or evidence of RAS (renal artery stenosis)

2. Pregnant

3. HIV

4. taking medications for diabetes, hyperlipidemia, cardiac disease, Medications for birth control, psychiatirc conditions, and sleep are Ok. Vitamins and herbs are Ok if continued throughout the study. Thyroid meds are acceptable if the TSH is within normal limits.

5. Diabetes as defined by hemoglobin A1c > 6.5% and/or fasting glucose > 125 mg/dl

6. Hyperlipidemia as defined by triglycerides >200 and/or LDL > 150

7. Hematuria on screening

8. RAAS (Renin-Angiotensin-Aldosterone) axis deviation - Aldosterone and Renin should be within normal ranges upon screening.

9. BUN > 40mg/dL corrected to body surface area

10. Creatinine > 1.3 mg/dL corrected to body surface area

11. BMI > 29.9 or < 19

12. Current smoker

13. Currently, a vegetarian (who does not consume fish and dairy) or a vegan

14. Based on medical history, any evidence of an autoimmune disease

15. Use of any of the following - ACEi, ARB, spironolactone, diuretics of any class, beta blockers, alpha blockers, nsaids, within the past two weeks

16. Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rockefeller University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dana Bielopolski, MD PhD

Role: PRINCIPAL_INVESTIGATOR

The Rockefeller University

Locations

The Rockefeller University

New York, New York, United States

Countries

United States

Other Identifiers

DBI-1000

Identifier Type: -

Identifier Source: org_study_id