The Role of Skin Sodium Accumulation in Chronic Kidney Disease

NCT07020104 | Recruiting DMC

• 1 other identifier: NL82810.018.22
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Diseases

Keywords

Skin sodium; Sodium MRI; CKD; Prognosis; Cardiovascular event; Renal event; Quality of life; Tissue sodium

Outcome Measures

Primary Outcomes (7)

• Skin sodium content at baseline (A)

  Skin sodium content will be measured using the 7T sodium MRI

  0 week

• Muscle sodium content at baseline (A)

  Muscle sodium content will be measured using the 7T sodium MRI

  0 week

• Change from baseline in tissue sodium content after low and high sodium diet (B)

  2 weeks

• Change in tissue sodium content after treatment with hydrochloorthiazide, spironolacton and lercanidipine (C)

  To study the effect of hydrochloorthiazide, spironolacton and lercanidipine on tissue sodium content, to compare the effect among the various antihypertensive agents and to assess the effect of blood pressure regulation, increased renal sodium excretion and aldosteron blockade on tissue sodium content.

  6 weeks

• Change from baseline in tissue sodium content after habitual and high water intake (D)

  To evaluate the effect of high and habitual water intake on tissue sodium content.

  4 weeks

• Change from baseline in transepidermal water loss after habitual and high water intake (D)

  To evaluate the effect of high and habitual water intake on transepidermal water loss.

  4 weeks

• Incidence of hyponatremia and hypervolemia (D)

  Safety of high water intake in CKD patients with eGFR between 15 and 30ml/min/1.73m2

  4 weeks

Secondary Outcomes (27)

• Correlation between tissue sodium content and total vessel density (A)

  0 week

• Correlation between tissue sodium content and perfused vessel density (A)

  0 week

• Correlation between tissue sodium content and proportion of perfused vessels (A)

  0 week

• Correlation between tissue sodium content and microvascular flow index (A)

  0 week

• Correlation between tissue sodium content and microvascular health score (A)

  0 week

Other Outcomes (6)

• Skin water content at baseline (A)

  0

• Muscle water content at baseline (A)

  0 week

• Change from baseline in skin water content (B/C/D)

  2 weeks

Study Arms (3)

Sodium excretion intervention (C)

EXPERIMENTAL

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

Drug: Hydrochlorothiazide; Drug: Spironolactone; Drug: Lercanidipine

Sodium intake intervention (B)

EXPERIMENTAL

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

Dietary Supplement: High sodium dietary intake (>200mmol/l); Dietary Supplement: Low sodium dietary intake (<50mmol/l)

Water intake intervention (D)

EXPERIMENTAL

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

Dietary Supplement: High water intake; Dietary Supplement: Habitual water intake

Interventions

Hydrochlorothiazide DRUG

Each patient will receive 1 tablet of hydrochlorothiazide 12.5mg once a day for the first 3 weeks of the drug cycle. If clinical and biochemical parameters allow, the dosage is doubled to 2 tablets of hydrochlorothiazide 12.5mg once daily for the following 3 weeks. If the laboratory results and clinical parameters do not allow dose intensification, the initial dosage will be continued during the second half of the drug cycle.

Sodium excretion intervention (C)

Spironolactone DRUG

Each patient will receive 1 tablet of spironolacton 12.5mg once a day for the first 3 weeks of the drug cycle. If clinical and biochemical parameters allow, the dose is doubled to 2 tablets of spironolacton 12.5mg once daily for the following 3 weeks. If the laboratory results and clinical parameters do not allow dose intensification, the initial dosage will be continued during the second half of the drug cycle.

Sodium excretion intervention (C)

Lercanidipine DRUG

Each patients will receive 1 tablet of lercanidipine 10mg once a day for the first 3 weeks of the drug cycle. If clinical and biochemical parameters allow, the dose is doubled to 2 tablets of lercanidipine 10mg once daily for the following 3 weeks. If the laboratory results and clinical parameters do not allow dose intensification, the initial dosage will be continued during the second half of the drug cycle.

Sodium excretion intervention (C)

High sodium dietary intake (>200mmol/l) DIETARY_SUPPLEMENT

The patients will receive a 2-week high sodium diet. The patients will receive dietary advice to achieve this goal of \>200mmol/l sodium (\>12g salt) intake per day.

Sodium intake intervention (B)

Low sodium dietary intake (<50mmol/l) DIETARY_SUPPLEMENT

The patients will receive a 2-week low sodium diet. The patients will receive dietary advice to achieve this goal of \<50mmol/l sodium (\<3g salt) intake per day.

Sodium intake intervention (B)

High water intake DIETARY_SUPPLEMENT

During the increased water intake period, the patients will be instructed to drink 1 L more than their mean 24-hour urine volume at screening and baseline.

Water intake intervention (D)

Habitual water intake DIETARY_SUPPLEMENT

During this part of the intervention, the patients will be instructed to maintain their habitual water intake.

Water intake intervention (D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m2.
• Stable diuretic and antihypertensive treatment for the previous 6 weeks.
• Chronic kidney disease with an eGFR between 15 and 29 ml/min/1.73m2
• Office blood pressure ≥140/90 mmHg or use of antihypertensive medication
• Fasting morning urine osmolality \<425 mOsm/kg for men and \< 400 mOsm/kg for women

You may not qualify if:

• Age \<18 years.
• The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months.
• (Recurrent) acute glomerulonephritis within 1 year prior to the study.
• Salt losing nephropathy.
• Use of oral or intravenous glucocorticoids with an equivalent of prednisolone \>5mg/day.
• Contra-indication for MRI.
• Cardiovascular event/ surgery in the previous 3 months.
• Pregnant women, women of child bearing age planning to conceive for the study duration, women of child bearing age without contraception.
• Participation in other (pharmacological) intervention studies.
• Presence of significant comorbidities with a life expectancy of less than 1 year.
• Disorder that compromises the participants' ability to give truly informed consent for participation in this study.
• Patients with an active infection and/or auto-immune diseases with involvement of the lower extremities.
• Any other issues that in opinion of the investigator could be harmful to the subject or compromise interpretation of the data.
• \. Chronic use of NSAID
• Serum potassium concentration \>5.0 mmol/l.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Dutch Kidney Foundation: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam-Zuidoost, North Holland, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Hydrochlorothiazide; Spironolactone; lercanidipine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rik Olde Engberink, MD, PhD

  Amsterdam UMC, location AMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rik Olde Engberink, MD, PhD

CONTACT

+31 0205669111; r.h.oldeengberink@amsterdamumc.nl

Sanédy Simon, MD

CONTACT

0205661930; s.s.a.simon@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Internist-nephrologist, clinical pharmacologist

Model Details: 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.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: June 13, 2025
• Study Start: January 7, 2025
• Primary Completion (Estimated): December 1, 2039
• Study Completion (Estimated): December 1, 2039
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)