Effect of Low Salt and Ckd Progression

Study Overview
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Brief Summary
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Whether an intensive short-term dietary sodium restricted intervention will have beneficial effects on the glomerular filtration rate (GFR) and on the susceptibility to develop proteinuria, both measures of kidney function will be the objective of this study

Detailed Description
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The prevalence of non-communicable disease (NCD including cardiovascular disease (CVD), diabetes mellitus (DM),hypertension(HT) and chronic kidney disease(CKD) continues to rise all over the world and lead to global crisis.The world Health Organization (WHO) shows that more than 50% of the burden of diseases arise from NCD and 30% is attributed to CVD[1] .In Thailand,the prevalence of high blood pressure in population age > 15 is increasing in the past 10 years .In 2022 the HT prevalence was 21.4 and the admission rate of CVD increased from 109.4 to 793.3 per 100,000 population [2]. Cumulating evidence highlights that higher sodium consumption contributes to higher BP [3], thus increasing the risk of cardiovascular disease (CVD) [4,5]. According to the World Health Organization, the restriction of sodium intake to less than 2.3 g/day of sodium corresponding to 5.8 g of salt (or 100 mmol) is one of the most cost-effective measures to improve public health [6]. In particular, in a large cohort study in over 100,000 patients from 18 countries the role of higher salt consumption was associated with increased BP levels [7], and poor CV outcomes [8].In one meta-analysis ,reduce salt intake to 1,800 mg per day will help reduce blood pressure by 2/1 mmHg in non-hypertensive cohorts and 5/2.7 mmHg in hypertensive patients [4].In fact, even minor sodium restriction for only 700-800 mmol/day was associated with reduction of CVD and mortality risks for 20 and 5-7% respectively. A long-standing line of evidence also shows beneficial effects of salt reduction in patients with chronic kidney disease (CKD) as well as in healthy people [9,10]. A recent review of the evidence for the relationship between salt intake and CKD progression concluded there is consistent evidence to suggest that dietary salt intake is linked with albuminuria and tissue injury [9] [11]. High salt intake is closely associated with the progression of CKD. When the urine sodium-to-creatinine ratio increases by 100 mmol/L, the risk of CKD developing into end-stage renal disease (ESRD) increases by 1.61 times [12,13]. High salt intake leads to renal impairment in various ways, including increasing transforming growth factor (TGF)-β1 production and enhancing oxidative stress and inflammatory response kidney [14-16]. The Lowsalt CKD trial trials had shown that in patients with CKD, salt reduction will have additional beneficial effects on renal effects, reduction of proteinuria,independent of blood pressure lowering effect. reported that salt reduction helped control blood pressure,reduce proteinuria [17] .However,the follow up time was too short. Meta-analysis data from Garofalo et al [18] indicates that low sodium intake ( 4.4 gm/day) in 738 CKD patients from 9 studies significantly reduce systolic blood pressure by 4.9 mmHg (95%CI 6.8/31 mmHg, p <0.001) .The diastolic blood pressure also reduce by 2 mmHg (95%CI 6.8/3.1 mmHg, P<0.001) .In CRIC study[19] which followed a cohort of 3,757 CKD patients for nearly 7 years,the authors found that the high urine sodium group (UNaV > 195 mmoL/day) significantly increased risk for CKD progression and CVD risk. These data support the evidence that reducing dietary sodium can reduce cardiovascular risk and rate of CKD progression. However, restriction in dietary sodium intake also activates the renin-angiotensin -aldosterone system (RAAS) and sympathetic nervous system[20,21].Low dietary sodium has been reported to be associated with insulin resistance [22]. To date, the connection between sodium intake and CKD progression provided inconsistent results [23]. Although several studies have shown that high dietary sodium intake increases the risk of CKD development or progression [24-26], some results failed to find significant connections to renal outcome [27-30]. In addition, there have also been reports that lower 24-hour urine sodium excretion is associated with higher risk of death and ESRD in individuals with type 1 and type 2 diabetes with overt proteinuria [30,31]. Whether an intensive short-term dietary sodium restricted intervention will have beneficial effects on the glomerular filtration rate (GFR) and on the susceptibility to develop proteinuria, both measures of kidney function will be the objective of this study

Official Title
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The Effect of Low Salt Diet on CKD Progression:A Randomized Controlled Trial

Conditions
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Proteinuria, CKD Progression, Blood Pressure

Intervention / Treatment
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* Dietary Supplement: Low salt diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: years with CKD stage 1-3 (estimated glomerular filtration rate (eGFR) of 30-59 ml/min per 1·73 m2 No recent history of acute illness or hospitalization BP >135/85 mmHg or controlled BP with the use of antihypertensive medications. Exclusion Criteria: Serious primary diseases affecting major organs such as the heart, brain, lung, liver, or hematopoietic system Active cancers Acute infectious diseases Pregnancy Post solid organs transplantation Terminally ill.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective open labelled randomized controlled trial study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The low sodium diet will be provided low salt diet 1.5 gm/day in three main meals for three months.The food will be provided by the nutritionists and delivered directly to their home | Dietary Supplement: Low salt diet<br>* Low salt diet less than 2 gram per day<br>|
| Placebo Comparator: Control<br>The control group will continue with their usual diet and record the food recall | Dietary Supplement: Low salt diet<br>* Low salt diet less than 2 gram per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of GFR decline | estimeated glomerular filtration rate | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure status | Blood pressure | 3 months | 
| Acid-base status | Electrolyte level | 3 months | 
| Calcium-phosphate balance | calcium,phosphorus level | 3 months | 
| Proteinuria | 24 hour urine protien level | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD progression, Low salt, Randomized controlled trial