The aim of this study is to investigate in salt-sensitive kidney patients the effect of two different dietary sodium regimens on BP and body fluid volume. Furthermore, we aim to evaluate the way in which new sodium handling mechanisms (interstitial…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Fysiologie van natrium- en volumebalans
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to explore in DKK and CKD patients the
effects of dietary sodium on body fluid volume, as measured by BP, weight and
bio-impedance measurements.
Secondary outcome
Secundary study parameters are expressed as the effect of salt intake on:
- Skin sodium concentration
- Microcirculatory changes
- Glycosaminoglycan metabolism
- Macrophage activation and lymphangiogenesis
- Microbiome content
Background summary
The role of sodium consumption in blood pressure (BP) regulation and
extracellular fluid (ECF) maintenance is a heavily debated topic. For a
substantial time, it was thought that sodium increases BP solely via an
increase in ECF. However, this assumption was challenged by several sodium
balance studies. Sodium intervention studies revealed two different mechanisms
which are relevant for sodium homeostasis. Highly sulphated glycosaminoglycans
(GAGs) in the interstitial space and the endothelium facilitate a third
compartment for non-osmotic sodium buffering. In various patients groups,
increased sodium buffering as measured with 23Na-MRI is associated with
sodium-sensitive hypertension. This finding suggests a causal relation between
non-osmotic sodium buffering and sodium-mediated BP development. Furthermore,
it has been demonstrated that interstitial sodium buffering is associated with
the activation of macrophages and alterations in the lymphangiogenesis and
microcirculation, which in turn relate to BP. There is also increasing
literature on the influence of the gut microbiome in the absorption of
macronutrients, including salt, while salt intake also has a major influence on
the composition of the gut microbiome. It is still unclear how this correlates
with blood pressure changes.
Study objective
The aim of this study is to investigate in salt-sensitive kidney patients the
effect of two different dietary sodium regimens on BP and body fluid volume.
Furthermore, we aim to evaluate the way in which new sodium handling mechanisms
(interstitial sodium storage, glycosaminoglycan metabolism, immune system
activation, microcirculatory changes and microbioma) are involved in this
effect.
Study design
This study is a randomized experimental interventional cross-over study design.
Intervention
High salt diet (>200 mmol Na+ daily) for 1 week and low salt diet (<50 mmol Na+
daily) for 1 week, each in random order.
Study burden and risks
The burden of this study consists of a total of 3 study visits in which they
spend about 10 hours in the hospital. Furthermore we ask patients to visit the
hospital 6 times for hand-in their collected 24-hour urine or pick up the
automatic device for 24-hour BP measurements, this will take ad maximum 50
minutes extra in the AMC. All participants will be asked to adhere to a low and
high Na+ diet and collect 24-hour urine samples during these diets. The study
comprises extra venous blood drawing and various extra diagnostic test.
Invasive measurements with sodium biopsies are also part of the study visits.
At present sodium homeostasis and the pathophysiology behind salt-sensitivity
in kidney patients is not well understood. In clinical pratice kidney patients
are advised to restrict their sodium consumption, however this is very
difficult for most patients.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
All subjects:
- Men and women Between 18 and 75 years of age
- Office blood pressure <= 140/90 mmHg
- A body mass index <= 30 kg/m2
- Capable of giving written informed consent and able to comply with the
requirements and restrictions listed in the informed consent form
Microalbuminuric type 2 diabetes patients:
- Known with Diabetes Mellitus type 2
- Either albuminuria (20-200 mg/L in a morning urine sample / 30-300 mg/24 hrs)
- Stable renal function (eGFR 45-90 ml/min/1.73m2) with or without on stable
therapy with RAAS inhibiting agents
- HbA1c levels below 10.0% (86mmol/mol) during the 6 months preceding the study
Nondiabetic CKD patients
- Known with CKD stage 2 - 3a
- Stable renal function during the 6 months preceding the study (eGFR 45-90
ml/min/1.73m2) with or without on stable therapy with RAAS inhibiting agents
- Albuminuria (> >200 mg/L in a morning urine sample / 500 - 3000mg/24 hrs)
Exclusion criteria
- An office blood pressure >140/90 mmHg;
- A body mass index >30 kg/m2;
- Use of systemic corticosteroids;
- Use of NSAIDs > 2 times a week;
- A major illness in the past 3 months of any significant chronic medical
illness that the Investigator would deem unfavourable enrolment, including
chronic inflammatory diseases, excluding the diseases of interest (DM2 and CKD)
;
- A history of any type of malignancy within the past 5 years with the
expectation of successfully treated basal cell cancer of the skin;
- A history of any auto-immune disease ;
- A history of cardiovascular disease (in the past 6 months) defined as
documented coronary artery disease including myocardial infarction, (un-)stable
angina pectoris or acute coronary syndrome, percutaneous transluminal coronary
angioplasty, coronary artery bypass grafting, cerebrovascular disease including
ischemic and haemorrhagic stroke or a subarachnodial bleeding, or peripheral
artery disease including aortic aneurysmata;
- A history of eye surgery, glaucoma of retinal disorder;
- A history, within 3 years, of drug abuse (including benzodiazepines, opioids,
amphetamine, cocaine, THC, methamphetamine);
- A history of alcoholism and/or drinking more than 3 units of alcohol per day.
Alcoholism is defined as an average weekly intake of >21 units for males. One
unit is equivalent to 9 g of alcohol: a half-pint (~ 240mL) of beer, 1 glass
(125 mL) of wine or 1 (25ml) measure of spirits;
- Smoking or use of tobacco products less than 30 days ago;
- Any other issue that in opinion of the Investigator could be harmful to the
subject or compromise interpretation of the data.
Design
Recruitment
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70705.018.19 |