When the Kidney Reacts to Nutritional Changes
Condition: Prehypertension
MeSH terms: Prehypertension
Study type: Interventional

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.
    

Intervention name(s): DASH
Intervention type(s): Other
Intervention description(s): 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 model: Single Group Assignment
Intervention model description: This study assesses how nutritional changes, namely DASH diet, change the composition of ion channels in the renal tubule, as exemplified by urine electrolyte ratio.
Masking: None (Open Label)
Primary purpose: Other
Keywords: inpatient; nutrition