The Role of Skin Sodium Accumulation in Chronic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Skin sodium content at baseline (A)
研究概览
简要总结
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.
详细描述
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):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic kidney disease with an eGFR between 15 and 60 ml/min/1.73m
- •Stable diuretic and antihypertensive treatment for the previous 6 weeks.
- •Additional inclusion criteria for the sodium excretion intervention
- •Office systolic blood pressure (SBP) >135 mmHg
- •Additional inclusion criteria for the water intervention
- •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
排除标准
- •Age <18 years.
- •The patient is expected to start renal replacement therapy or is planned to receive a kidney transplantation within 3 months.
- •An active diagnosis of nephrotic syndrome at inclusion.
- •(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.
- •Additional exclusion criteria for the sodium intake intervention
- •Chronic use of NSAID
- •Additional exclusion criteria for the sodium excretion intervention
- •Serum potassium concentration >5.0 mmol/l.
- •eGFR <30 ml/min/1.73m2
- •Uncontrolled hypertension (>180/100 mmHg)
- •Severe heart failure with left ventricular ejection fraction <30%.
- •Contra-indication for investigational drugs.
- •Severe symptoms of (orthostatic) hypotension.
- •Patients with obstruction of the outflow tract of the left ventricle such as aortic valve stenosis.
- •Refractory hypokalemia, hyponatremia or hypercalcemia.
- •Severe liver insufficiency Child Pugh B/C
- •Chronic use of NSAID.
- •Additional exclusion criteria for the water intake intervention
- •Recent history of severe hyponatremia (outpatient plasma sodium < 130 mmol/L in the last 6 months)
- •Plasma sodium <135 mmol/L at screening
- •History of heart failure
- •Use of lithium, vasopressin analoga, vasopressin antagonists, oral or intravenous glucocorticoids, thiazide diuretics.
- •24-hour urine volume > 2L
- •Chronic use of NSAID
研究组 & 干预措施
Sodium excretion intervention (C)
In this intervention group, the patients will receive three antihypertensive drugs in a randomized order. Thus the following orders are possible:
- Lercanidipine - Spironolactone - Hydrochlorothiazide
- Lercanidipine - Hydrochlorothiazide - Spironolactone
- Hydrochlorothiazide - Lercanidipine - Spironolactone
- Hydrochlorothiazide - Spironolactone - Lercanidipine
- Spironolactone - Lercanidipine - Hydrochlorothiazide
- Spironolactone - Hydrochlorothiazide- Lercanidipine
干预措施: Hydrochlorothiazide (Drug)
Sodium excretion intervention (C)
In this intervention group, the patients will receive three antihypertensive drugs in a randomized order. Thus the following orders are possible:
- Lercanidipine - Spironolactone - Hydrochlorothiazide
- Lercanidipine - Hydrochlorothiazide - Spironolactone
- Hydrochlorothiazide - Lercanidipine - Spironolactone
- Hydrochlorothiazide - Spironolactone - Lercanidipine
- Spironolactone - Lercanidipine - Hydrochlorothiazide
- Spironolactone - Hydrochlorothiazide- Lercanidipine
干预措施: Spironolactone (Drug)
Sodium excretion intervention (C)
In this intervention group, the patients will receive three antihypertensive drugs in a randomized order. Thus the following orders are possible:
- Lercanidipine - Spironolactone - Hydrochlorothiazide
- Lercanidipine - Hydrochlorothiazide - Spironolactone
- Hydrochlorothiazide - Lercanidipine - Spironolactone
- Hydrochlorothiazide - Spironolactone - Lercanidipine
- Spironolactone - Lercanidipine - Hydrochlorothiazide
- Spironolactone - Hydrochlorothiazide- Lercanidipine
干预措施: Lercanidipine (Drug)
Sodium intake intervention (B)
In this intervention group, the patients will receive two sodium diets in a randomized order. The following orders are possible:
- High sodium intake- Low sodium intake
- Low sodium intake- High sodium intake
干预措施: High sodium dietary intake (>200mmol/l) (Dietary Supplement)
Sodium intake intervention (B)
In this intervention group, the patients will receive two sodium diets in a randomized order. The following orders are possible:
- High sodium intake- Low sodium intake
- Low sodium intake- High sodium intake
干预措施: Low sodium dietary intake (<50mmol/l) (Dietary Supplement)
Water intake intervention (D)
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
干预措施: High water intake (Dietary Supplement)
Water intake intervention (D)
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
干预措施: Habitual water intake (Dietary Supplement)
结局指标
主要结局
Skin sodium content at baseline (A)
时间窗: 0 week
Skin sodium content will be measured using the 7T sodium MRI
Muscle sodium content at baseline (A)
时间窗: 0 week
Muscle sodium content will be measured using the 7T sodium MRI
Change from baseline in tissue sodium content after low and high sodium diet (B)
时间窗: 2 weeks
Change in tissue sodium content after treatment with hydrochloorthiazide, spironolacton and lercanidipine (C)
时间窗: 6 weeks
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.
Change from baseline in tissue sodium content after habitual and high water intake (D)
时间窗: 4 weeks
To evaluate the effect of high and habitual water intake on tissue sodium content.
Change from baseline in transepidermal water loss after habitual and high water intake (D)
时间窗: 4 weeks
To evaluate the effect of high and habitual water intake on transepidermal water loss.
Incidence of hyponatremia and hypervolemia (D)
时间窗: 4 weeks
Safety of high water intake in CKD patients with eGFR between 15 and 30ml/min/1.73m2
次要结局
- 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)
- Correlation between tissue sodium content and total pheripheral resistance (A)(0 week)
- Correlation between tissue sodium content and cardiac output (A)(0 week)
- Correlation between tissue sodium content and transepidermal water loss (A)(0 week)
- Correlation between tissue sodium content and office systolic and diastolic blood pressure (A)(0 week)
- Correlation between tissue sodium content and quality of life (A)(At baseline and yearly during follow-up)
- Correlation between tissue sodium content and 24-hour systolic and diastolic blood pressure (A)(0 week)
- Correlation between tissue sodium content and nightime blood pressure dipping pattern (A)(0 week)
- Correlation between tissue sodium content and total body water (A)(0 week)
- The correlation between tissue sodium content and traditional cardiovascular risk factors (A)(15 years)
- Change from baseline in plasma co-peptine concentrations (D)(4 weeks)
- Change from baseline in seated systolic and diastolic office blood pressure (B/C/D)(2 weeks)
- Change from baseline in 24-hour systolic and diastolic blood pressure (B/C/D)(2 weeks)
- Change from baseline in percentage of patients with a night-time blood pressure dipping pattern (B/C/D)(2 weeks)
- Change from baseline in transepidermal water loss (B/C/D)(2 weeks)
- Change from baseline in total body water (B/C/D)(2 weeks)
- Change from baseline in total vessel density (B/C/D)(2 weeks)
- Change from baseline in perfused vessel density (B/C/D)(2 weeks)
- Change from baseline in proportion of perfused vessel (B/C/D)(2 weeks)
- Change from baseline in microvascular flow index (B/C/D)(2 weeks)
- Change from baseline in microvascular health score (B/C/D)(2 weeks)
- Change from baseline in total peripheral resistance (B/C/D)(2 weeks)
- Change from baseline in cardiac output (B/C/D)(2 weeks)
研究者
Rik Olde Engberink
Internist-nephrologist, clinical pharmacologist
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)