Hypertension
Conditions
Brief summary
High dietary phosphate intake in the general population is associated with a higher risk for developing kidney disease and cardiovascular disease with an increased overall mortality. Whereas the effects of high phosphate intake on general health become clearer, almost nothing is known about underlying mechanisms. More recently, the investigators and others found in animal models that FGF23 stimulates the renal NaCl cotransporter NCC, the target of thiazide diuretics, and that increased NCC activity may increase blood pressure. The investigators could also show that increasing dietary phosphate intake in mice, increases FGF23 and NCC activity within 3 days. Thus, the objective of this single-centre observational cross-over study including 20-45 year old healthy male probands is to elucidate the role of dietary phosphate on blood pressure regulation and renal handling of sodium chloride in healthy subjects. Further the impact of dietary phosphate intake on the regulation of phosphaturic hormones and other factors regulation blood pressure will be investigated. In addition, the investigators will examine whether phosphate intake modulates gut microbiome composition. The primary outcome in this study is the change in blood pressure in healthy subjects on low-phosphate diet compared to healthy subjects on high-phosphate diet. In addition, to assess changes in NCC activity as the main mechanism of phosphate-sensitive blood pressure regulation, renal sodium chloride excretion after administration of hydrochlorothiazide will be measured. The secondary outcomes of this study are: changes in renal phosphate, calcium and potassium excretion, changes in phosphate regulation hormones such as 25-OH-Vit. D, 1,25-(OH)2-Vit. D, PTH, FGF23, dopamine in plasma and urine, changes in plasma and urinary aldosterone levels, changes in sodium/chloride-cotransporter NCC and NaPi-IIa assessed from urinary exosomes, and changes in stool phosphate excretion and gut microbiome composition.
Interventions
DIETARY_SUPPLEMENTsodium phosphate
DRUGsevelamer, sodium bicarbonate, sodium chloride
Sponsors
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 20-45 year old healthy male subjects
Exclusion criteria
* \- Kidney disease (defined by eGFR \< 90 ml/min or microalbuminuria (\> 30mg/d)) * Diabetes mellitus * Hypertension (RR \> 140/85 mmHg) * Hypotension (RR \< 90/60 mmHg) * any regular medication * non-Western type diet e.g. vegetarian, vegan etc. * History of kidney stones * Allergy to sulphonamides or penicillins * Hereditary fructose intolerance * known hypersensitivity or allergy to class of drugs used in this study * Glaucoma * Vitamin D deficiency (\< 20 ng/ml) * Hyper- or Hypoparathyroidism * Hypo- or hyperaldosteronism * Participation in any other study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in blood pressure | 5 days |
| Change in renal sodium chloride excretion | 5 days |
Countries
Switzerland
Outcome results
None listed