Clinical trial NCT07020104: The Role of Skin Sodium Accumulation in Chronic Kidney Disease
Official title: The Role of Skin Sodium Accumulation in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Keywords: Skin sodium
Sodium MRI
CKD
Prognosis
Cardiovascular event
Renal event
Quality of life
Tissue sodium
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Dutch Kidney Foundation
First posted: 2025-06-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The association between tissue sodium accumulation and cardiovascular parameters, body composition, skin hydration and transepidermal water loss, renal and cardiovascular outcome will be studied in 60 CKD patients (A).

14 of the 60 CKD patients will be randomized to a 2-week low sodium diet and a 2-week high sodium diet in an open-label cross-over manner (B).

12 CKD patients will receive 3 antihypertensive agents (spironolactone, lercanidipine and hydrochlorothiazide) in random order for 6 weeks (C).

12 of the 60 CKD subjects will be randomized to a 4 week increased water intake and 4 week habitual water intake (D).

All the intervention mentioned above are separated by a washout period of at least 2 weeks between interventions.
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Skin sodium content at baseline (A)
timeFrame: 0 week
measure: Muscle sodium content at baseline (A)
timeFrame: 0 week
measure: Change from baseline in tissue sodium content after low and high sodium diet (B)
timeFrame: 2 weeks
measure: Change in tissue sodium content after treatment with hydrochloorthiazide, spironolacton and lercanidipine (C)
timeFrame: 6 weeks
measure: Change from baseline in tissue sodium content after habitual and high water intake (D)
timeFrame: 4 weeks
measure: Change from baseline in transepidermal water loss after habitual and high water intake (D)
timeFrame: 4 weeks
measure: Incidence of hyponatremia and hypervolemia (D)
timeFrame: 4 weeks
Secondary outcomes:
measure: Correlation between tissue sodium content and total vessel density (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and perfused vessel density (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and proportion of perfused vessels (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and microvascular flow index (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and microvascular health score (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and total pheripheral resistance (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and cardiac output (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and transepidermal water loss (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and office systolic and diastolic blood pressure (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and 24-hour systolic and diastolic blood pressure (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and nightime blood pressure dipping pattern (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and total body water (A)
timeFrame: 0 week
measure: Correlation between tissue sodium content and quality of life (A)
timeFrame: At baseline and yearly during follow-up
measure: The correlation between tissue sodium content and traditional cardiovascular risk factors (A)
timeFrame: 15 years
measure: Change from baseline in plasma co-peptine concentrations (D)
timeFrame: 4 weeks
measure: Change from baseline in seated systolic and diastolic office blood pressure (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in 24-hour systolic and diastolic blood pressure (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in percentage of patients with a night-time blood pressure dipping pattern (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in transepidermal water loss (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in total body water (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in total vessel density (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in perfused vessel density (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in proportion of perfused vessel (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in microvascular flow index (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in microvascular health score (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in total peripheral resistance (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in cardiac output (B/C/D)
timeFrame: 2 weeks
Other outcomes:
measure: Skin water content at baseline (A)
timeFrame: 0
measure: Muscle water content at baseline (A)
timeFrame: 0 week
measure: Change from baseline in skin water content (B/C/D)
timeFrame: 2 weeks
measure: Change from baseline in muscle water content (B/C/D)
timeFrame: 2 weeks
measure: Association between tissue sodium content and skin hydration (A)
timeFrame: 0 week
measure: Change from baseline in skin hydration (B/C/D)
timeFrame: 2 weeks
Locations:
city: Amsterdam-Zuidoost
country: Netherlands
facility: Amsterdam UMC
state: North Holland
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Rik Olde Engberink, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: