Role of endothelial surface layer in regulating the sodium balance and extracellular fluid volume

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Diabetic patients (n<=12)
- Male between 18 and 40 years old
- Known with Diabetes Mellitus - type 1
- With or without microalbuminuria defined as:
o either albuminuria 20-200 mg/L in a morning urine sample
o or albuminuria 30-300 mg/24 hrs collected in a 24-hours urine collection
o or albumin-to-creatinin ratio 2,5-25 mg/mmol in a morning urine sample.
- Stable renal function (creatine clearance > 60 ml/min and < 6 ml/min per year decline) with or without stable therapy with RAAS inhibiting agents
- HbA1c levels between 6.0 and 10.0% (42-86 mmol/mol) during the 6 months preceding the study
- Multiple injections of insulin a day
- Able to provide written informed consent and to comply with the requirements and restrictions listed in the informed consent form;2. HME patients (n<=12)
- Male between 18 and 40 years old
- Documented Hereditary Multiple Exostoses
- Stable renal function (creatinin clearance > 60 ml/min and < 6 ml/min per year decline, no proteinuria)
- Able to provide written informed consent and to comply with the requirements and restrictions listed in the informed consent form

Exclusion Criteria

- An office blood pressure >140/90 mmHg
- A body mass index > 30 kg/m2
- A major illness in the past 3 months or any significant chronic medical illness that the Investigator would deem unfavourable for enrolment, including chronic inflammatory diseases
- A history of any type of malignancy within the past 5 years with the exception of successfully treated basal cell cancer of the skin
- A history of any renal 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, precutenaous transluminal coronary angioplasty, coronary artery bypass grafting, cerebrovascular disease including ischemic and hemorrhagic stroke or a subarachnodial bleeding, or peripheral artery disease including aortic aneurysmata
- A history of coagulation disorders
- A history of primary hyperlipoproteinemias
- A history of hypersensitivity or allergy to iodium or to shell fish
- A history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine)
- A history of alcoholism and/or is 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 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
- Difficulty in donating blood or limited accessibility of a vein in left and right arm
- Subject has donated blood in last 3 months
- Use of tobacco products
- Any other issue that, in the opinion of the Investigator, could be harmful to the subject or compromise interpretation of the data
- Any clinically relevant abnormality noted on the 12-lead ECG as judged by the Investigator or an average QTcB or QTcF > 450 millisec

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>We will primarily study the effects of a salt load on the haemodynamics, ECV<br /><br>and ESL in patients with acquired and congenital loss of the ESL. Primary<br /><br>endpoint will be the ECV as represented by body weight, BP and iohexol<br /><br>measurements. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Other study paramaters consist of indirect measurements of the ESL dynamics and<br /><br>function assessed by imaging of the sublingual microvasculature, measurement of<br /><br>ESL shedding products and determination of the transcapillary escape rate (TER)<br /><br>of I125-albumine. The kidney function will be studied by estimating the<br /><br>glomerular filtration rate (eGFR) and measurement of the fractional Na+<br /><br>excretion and albuminuria. Finally, skin biopsies will allow studying the role<br /><br>of interstitial GAGs and macrophage influx in response to a salt load.</p><br>

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