The Role of Skin Sodium Accumulation in Chronic Kidney Disease (SKIN-CKD)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status: Enrolling

Conditions: Chronic Kidney Diseases

Treatments: Dietary Supplement: High sodium dietary intake (>200mmol/l); Drug: Hydrochlorothiazide; Dietary Supplement: Low sodium dietary intake (<50mmol/l); Drug: Spironolactone; Dietary Supplement: High water intake; Drug: Lercanidipine; Dietary Supplement: Habitual water intake

Study type: Interventional

Funder types: Other

Identifiers

NCT07020104

NL82810.018.22

Details and patient eligibility

About

This project consists of four substudies: a cohort study (A) and a sodium intake intervention (B) and a sodium excretion intervention (C) and a water intervention study (D).

The main objective of the cohort study (A) is to investigate the prognostic implications of tissue sodium accumulation in CKD patients. The primary objective of the sodium intervention studies is to study the effect of high and low sodium intake (B) and increased renal sodium excretion (C) on tissue sodium content. The main objective of the water intervention study (D) is to investigate the effect of increased and habitual water intake on tissue sodium content and transepidermal water loss.

Full description

Cohort study (A):

60 CKD patients (eGFR 15 - 60 ml/min/1.73m2) are included in this cohort study. At the start of the study the association between tissue sodium content and micro-and macrovascular function will be evaluated. These patients will be followed up to investigate the association between tissue sodium content, quality of life and renal and cardiovascular events.

Sodium intake intervention (B):

A subgroup of 14 CKD patients (eGFR 15 - 60 ml/min/1.73m2) will be randomized to a 2-week low sodium diet and a 2-week high sodium diet in a cross-over study.

Sodium excretion intervention (C):

A subgroup of 12 CKD patients (eGFR 30 - 60 ml/min/1.73m2) with hypertension will be randomized to receive 6 weeks of treatment with hydrochlorothiazide, spironolactone and lercanidipine in a randomized open-label cross-over trial.

Water intake intervention (D) A subgroup of 12 CKD patients (with eGFR 15-30 ml/min/1.73m2, hypertension and fasting morning urine osmolality < 425 mOsm/kg for men and < 400 mOsm/kg for women) will be randomized to a 4-week habitual water intake and 4-week increased water intake in a cross-over study.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m2.
2. Stable diuretic and antihypertensive treatment for the previous 6 weeks.

Additional inclusion criteria for the sodium excretion intervention 1. Office systolic blood pressure (SBP) >135 mmHg

Additional inclusion criteria for the water intervention

1. Chronic kidney disease with an eGFR between 15 and 29 ml/min/1.73m2
2. Office blood pressure ≥140/90 mmHg or use of antihypertensive medication
3. Fasting morning urine osmolality <425 mOsm/kg for men and < 400 mOsm/kg for women

Exclusion criteria

1. Age <18 years.
2. The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months.
3. An active diagnosis of nephrotic syndrome at inclusion.
4. (Recurrent) acute glomerulonephritis within 1 year prior to the study.
5. Salt losing nephropathy.
6. Use of oral or intravenous glucocorticoids with an equivalent of prednisolone >5mg/day.
7. Contra-indication for MRI.
8. Cardiovascular event/ surgery in the previous 3 months.
9. Pregnant women, women of child bearing age planning to conceive for the study duration, women of child bearing age without contraception.
10. Participation in other (pharmacological) intervention studies.
11. Presence of significant comorbidities with a life expectancy of less than 1 year.
12. Disorder that compromises the participants' ability to give truly informed consent for participation in this study.
13. Patients with an active infection and/or auto-immune diseases with involvement of the lower extremities.
14. Any other issues that in opinion of the investigator could be harmful to the subject or compromise interpretation of the data.

Additional exclusion criteria for the sodium intake intervention

1. Chronic use of NSAID

Additional exclusion criteria for the sodium excretion intervention

1. Serum potassium concentration >5.0 mmol/l.
2. eGFR <30 ml/min/1.73m2
3. Uncontrolled hypertension (>180/100 mmHg)
4. Severe heart failure with left ventricular ejection fraction <30%.
5. Contra-indication for investigational drugs.
6. Severe symptoms of (orthostatic) hypotension.
7. Patients with obstruction of the outflow tract of the left ventricle such as aortic valve stenosis.
8. Refractory hypokalemia, hyponatremia or hypercalcemia.
9. Severe liver insufficiency Child Pugh B/C
10. Chronic use of NSAID.

Additional exclusion criteria for the water intake intervention

1. Recent history of severe hyponatremia (outpatient plasma sodium < 130 mmol/L in the last 6 months)
2. Plasma sodium <135 mmol/L at screening
3. History of heart failure
4. Use of lithium, vasopressin analoga, vasopressin antagonists, oral or intravenous glucocorticoids, thiazide diuretics.
5. 24-hour urine volume > 2L
6. Chronic use of NSAID

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Sodium excretion intervention (C)

Experimental group

Description:

In this intervention group, the patients will receive three antihypertensive drugs in a randomized order. Thus the following orders are possible: 1. Lercanidipine - Spironolactone - Hydrochlorothiazide 2. Lercanidipine - Hydrochlorothiazide - Spironolactone 3. Hydrochlorothiazide - Lercanidipine - Spironolactone 4. Hydrochlorothiazide - Spironolactone - Lercanidipine 5. Spironolactone - Lercanidipine - Hydrochlorothiazide 6. Spironolactone - Hydrochlorothiazide- Lercanidipine

Treatment:

Drug: Lercanidipine

Drug: Spironolactone

Drug: Hydrochlorothiazide

Sodium intake intervention (B)

Experimental group

Description:

In this intervention group, the patients will receive two sodium diets in a randomized order. The following orders are possible: 1. High sodium intake- Low sodium intake 2. Low sodium intake- High sodium intake

Treatment:

Dietary Supplement: Low sodium dietary intake (<50mmol/l)

Dietary Supplement: High sodium dietary intake (>200mmol/l)

Water intake intervention (D)

Experimental group

Description:

In this intervention group, the patients will be prescribed two water interventions in a randomized order. The following orders are possible: 1. High water intake- Habitual water intake 2. Habitual water intake- High water intake

Treatment:

Dietary Supplement: Habitual water intake

Dietary Supplement: High water intake