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| Name | Class |
|---|---|
| Dutch Kidney Foundation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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:
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| 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:
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| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between tissue sodium content and total vessel density (A) | Correlation between tissue sodium content measured with 7T Na-MRI and total vessel density using Sidestream Dark Field imaging. | 0 week |
| Correlation between tissue sodium content and perfused vessel density (A) |
| Measure | Description | Time Frame |
|---|---|---|
| Skin water content at baseline (A) | Skin water content will be measured using the 7T H-MRI | 0 |
| Muscle water content at baseline (A) | Muscle water content will be measured using the 7T H-MRI |
Inclusion Criteria:
Additional inclusion criteria for the sodium excretion intervention 1. Office systolic blood pressure (SBP) >135 mmHg
Additional inclusion criteria for the water intervention
Exclusion Criteria:
Additional exclusion criteria for the sodium intake intervention
1. Chronic use of NSAID
Additional exclusion criteria for the sodium excretion intervention
Additional exclusion criteria for the water intake intervention
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rik Olde Engberink, MD, PhD | Contact | +31 0205669111 | 27445 | r.h.oldeengberink@amsterdamumc.nl |
| Sanédy Simon, MD | Contact | 0205661930 | s.s.a.simon@amsterdamumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Rik Olde Engberink, MD, PhD | Amsterdam UMC, location AMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam UMC | Recruiting | Amsterdam-Zuidoost | North Holland | 1105AZ | Netherlands |
Individual participant data will not be shared with other researcher
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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.
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| 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. |
|
| 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. |
|
| 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. |
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| 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. |
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| 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. |
|
| Habitual water intake | Dietary Supplement | During this part of the intervention, the patients will be instructed to maintain their habitual water intake. |
|
| 4 weeks |
Correlation between tissue sodium content measured with 7T Na-MRI and perfused vessel density using Sidestream Dark Field imaging. |
| 0 week |
| Correlation between tissue sodium content and proportion of perfused vessels (A) | Correlation between tissue sodium content measured with 7T Na-MRI and proportion of perfused vessels using Sidestream Dark Field imaging. | 0 week |
| Correlation between tissue sodium content and microvascular flow index (A) | Correlation between tissue sodium content measured with 7T Na-MRI and microvascular flow index using Sidestream Dark Field imaging. | 0 week |
| Correlation between tissue sodium content and microvascular health score (A) | Correlation between tissue sodium content measured with 7T Na-MRI and microvascular health score using Sidestream Dark Field imaging. | 0 week |
| Correlation between tissue sodium content and total pheripheral resistance (A) | Total pheripheral resistance will be measured using the Nexfin device and tissue sodium content will be measured using the 7T Na-MRI | 0 week |
| Correlation between tissue sodium content and cardiac output (A) | Cardiac output will be measured using the Nexfin device and tissue sodium content will be measured using the 7T Na MRI | 0 week |
| Correlation between tissue sodium content and transepidermal water loss (A) | Transepidermal water loss will be measured with the Tewameter® TM Hex probe and tissue sodium content will be measured using the 7T Na MRI | 0 week |
| Correlation between tissue sodium content and office systolic and diastolic blood pressure (A) | Tissue sodium content will be measured using the 7T sodium MRI | 0 week |
| Correlation between tissue sodium content and 24-hour systolic and diastolic blood pressure (A) | Tissue sodium content will be measured using the 7T Na MRI | 0 week |
| Correlation between tissue sodium content and nightime blood pressure dipping pattern (A) | The nighttime blood pressure dipping pattern will be measured with a 24-hour blood pressure measurements. Patients will be classified as a 'dippers' when the nighttime systolic blood pressure and/or diastolic blood pressure falls >10% and <20% compared to daytime readings. Exteme dippers are described as those with blood pressure fall of at least 20%. Patients with blood pressure fall between 0 and 10% are classified as non-dippers. | 0 week |
| Correlation between tissue sodium content and total body water (A) | Total body water (liter) will be measured using the bioelectrical impendance analysis and tissue sodium content will be measured using the 7T Na MRI | 0 week |
| Correlation between tissue sodium content and quality of life (A) | Quality of life(QoL) will be measured with the Kidney Disease Quality of Life questionnaire at baseline and yearly during follow-up and tissue sodium comntent will be measured using the 7T Na MRI at baseline | At baseline and yearly during follow-up |
| The correlation between tissue sodium content and traditional cardiovascular risk factors (A) | In the cohort study, the correlation between tissue sodium content measured with 7T Na MRI and the known traditional cardiovascular risk factors will be studied. | 15 years |
| Change from baseline in plasma co-peptine concentrations (D) | For waterintake intervention study | 4 weeks |
| Change from baseline in seated systolic and diastolic office blood pressure (B/C/D) | Seated office systolic and diastolic blood pressure after interventions compared to baseline | 2 weeks |
| Change from baseline in 24-hour systolic and diastolic blood pressure (B/C/D) | 24-hour systolic and diastolic blood pressure after interventions compared to baseline | 2 weeks |
| Change from baseline in percentage of patients with a night-time blood pressure dipping pattern (B/C/D) | Nighttime blood pressure dipping status will be measured with a 24-hour blood pressure measurements. Patients will be classified as a 'dippers' when the nighttime systolic blood pressure and/or diastolic blood pressure falls >10% and <20% compared to daytime readings. Exteme dippers are described as those with blood pressure fall of at least 20%. Patients with blood pressure fall between 0 and 10% are classified as non-dippers. | 2 weeks |
| Change from baseline in transepidermal water loss (B/C/D) | Transepidermal water loss will be measured with the Tewameter® TM Hex probe | 2 weeks |
| Change from baseline in total body water (B/C/D) | Total body water will be measured using the bioelectrical impendance analysis | 2 weeks |
| Change from baseline in total vessel density (B/C/D) | The total vessel density will be measured using Sidestream Dark Field imaging. | 2 weeks |
| Change from baseline in perfused vessel density (B/C/D) | The perfused vessel density will be measured using Sidestream Dark Field imaging. | 2 weeks |
| Change from baseline in proportion of perfused vessel (B/C/D) | The proportion of perfused vessels will be measured using Sidestream Dark Field imaging. | 2 weeks |
| Change from baseline in microvascular flow index (B/C/D) | The microvascular flow index will be measured using Sidestream Dark Field imaging. | 2 weeks |
| Change from baseline in microvascular health score (B/C/D) | The microvascular health score will be measured using Sidestream Dark Field imaging. | 2 weeks |
| Change from baseline in total peripheral resistance (B/C/D) | The total pheripheral resistance will be measured using the Nexfin device | 2 weeks |
| Change from baseline in cardiac output (B/C/D) | The cardiac output will be measured using the Nexfin device | 2 weeks |
| 0 week |
| Change from baseline in skin water content (B/C/D) | Change in skin water content after sodium excretion, sodium intake and water intake intervention | 2 weeks |
| Change from baseline in muscle water content (B/C/D) | Change in muscle water content after sodium excretion, sodium intake and water intake intervention | 2 weeks |
| Association between tissue sodium content and skin hydration (A) | The skin hydration will be measured using the Corneometer® CM 825 probe | 0 week |
| Change from baseline in skin hydration (B/C/D) | The skin hydration will be measured using the Corneometer® CM 825 probe | 2 weeks |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D006852 | Hydrochlorothiazide |
| D013148 | Spironolactone |
| C060343 | lercanidipine |
| ID | Term |
|---|---|
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D049971 | Thiazides |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D007783 | Lactones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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