Effect of low salt diet on progression of chronic kidney disease: A prospective, open-label, randomized controlled trial

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Effect of low salt diet on progression of chronic kidney disease: A prospective, open-label, randomized controlled trial

https://doi.org/10.21203/rs.3.rs-3955317/v1

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A causal relationship between salt intake and hypertension, stroke, and kidney disease has been established. However, whether reduced salt intake leads to lower blood pressure has been intensely debated. In this prospective, open-label, randomized controlled trial, we examined the impact of low-salt diet on blood pressure, renal function, and other metabolic parameters. Herein, 194 patients with chronic kidney disease (CKD) stage 1–3 were randomized into the low-salt (intervention) and control groups. The intervention group was provided a salt diet (1.5 gm/day) for 3 months. The control group consumed their usual diet; daily food intake was recorded. Renal function tests; 24-hour urinary sodium excretion; urinary protein; and serum calcium, phosphorus, and electrolyte levels were recorded monthly. Blood pressure decreased significantly in both groups; systolic blood pressure reduction at 3 months was significantly greater in intervention group (-6.57, p < 0.001) compared to control group (-0.58, p = 0.072). Mean reduction in 24-hour urine sodium excretion were greater in intervention group and reached significant level at month 2 (-14.45, p = 0.032). Mean reduction in estimated glomerular filtration rate was significantly higher in control group. Thus, a sodium-restricted diet can help reduce blood pressure and slow the progression of renal insufficiency in patients with CKD.

ClinicalTrials.Gov Identifier: NCT05716386 on 28/01/2023

Health sciences/Health care

Health sciences/Nephrology

CKD progression

low-salt diet

randomized controlled trial

The global prevalence of noncommunicable diseases (NCD), including cardiovascular disease (CVD), diabetes mellitus (DM), hypertension (HTN), and chronic kidney disease (CKD), is on the rise, leading to a worldwide health crisis. The World Health Organization (WHO) reports that NCDs account for over 50% of the global disease burden, with CVDs contributing to 30% of this figure [1]. In Thailand, the prevalence of HTN in the population aged > 15 years has increased over the past 10 years; in 2022, the HTN prevalence was 21.4%, and the admission rate of CVDs increased from 109.4 to 793.3 per 100,000 population [2]. A growing body of evidence suggests that higher sodium consumption contributes to higher blood pressure (BP) [3], thereby increasing the risk of CVD [4, 5]. According to WHO, restricting sodium intake to < 2.3 g/day of sodium corresponding to 5.8 g of salt (or 100 mmol) is one of the most cost-effective measures for improving public health [6]. In a large cohort study of over 100,000 patients from 18 countries, higher salt consumption was associated with increased BP [7] and poor cardiovascular outcomes [8]. In one meta-analysis, reducing salt intake to 1,800 mg per day helped 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 of only 700–800 mmol/day was associated with 20% and 5–7% reduction in CVD and mortality risks, respectively.

A long-standing line of evidence also demonstrates the beneficial effects of salt reduction in patients with CKD, as well as in healthy people [9, 10]. A recent review of the evidence on the relationship between salt intake and CKD progression concluded that there is consistent evidence suggesting that dietary salt intake is linked to albuminuria and tissue injury [9, 11]. High salt intake is closely associated with CKD progression. Furthermore, 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 increased transforming growth factor (TGF)-β1 production and enhanced oxidative stress and inflammatory response by the kidney [14–16]. A trial evaluating the effect of low-salt diet on CKD progression demonstrated that in patients with CKD, salt reduction has additional beneficial effects on renal function and reduction of proteinuria, independent of the blood pressure-lowering effect; furthermore, salt reduction helps control blood pressure and reduce proteinuria [17]. However, the follow-up period of this trial was short. Garofalo et al. [18] performed a meta-analysis of nine studies including 738 patients with CKD; they reported that low sodium intake (4.4 gm/day) significantly reduced systolic BP by 4.9 mmHg (95% confidence interval [CI]: 6.8/31 mmHg, p < 0.001) and diastolic BP by 2 mmHg (95%CI: 6.8/3.1 mmHg, p < 0.001). In the CRIC study [19], which followed a cohort of 3,757 patients with CKD for nearly 7 years, the authors found that the high urine sodium group (> 195 mmoL/day) had a significantly increased risk of CKD progression and CVD. These data support the evidence that reducing dietary sodium can reduce cardiovascular risk and rate of CKD progression.

Moreover, restriction of dietary sodium intake also activates the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system [20, 21]. Low dietary sodium levels are reportedly associated with insulin resistance [22]. To date, studies on the association between sodium intake and CKD progression have yielded inconsistent results [23]. Although several studies have shown that high dietary sodium intake increases the risk of CKD development or progression [12, 13, 24], some studies have failed to find significant connections with renal outcome [25–28]. 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 [28, 29]. In this study, we aimed to determine whether an intensive short-term, sodium-restricted, dietary intervention will have beneficial effects on the glomerular filtration rate (GFR) and on the susceptibility to proteinuria, both measures of kidney function, in addition to blood pressure, and metabolic markers.

This prospective, open-label, randomized controlled trial was conducted from December 2022 to August 2023 at the Faculty of Medicine, Vajira Hospital and at a private hospital (Kasemrad Prachachuen Hospital). Written informed consent was obtained from all participants before their inclusion. This study was approved by the local ethics committees of both centers and complied with the Declaration of Helsinki. The Consolidated Standards of Reporting Trials (CONSORT) checklist was used as reference. This study was registered in The ClinicalTrials.Gov Identifier: NCT05716386 on 28/01/2023.

Participants and Randomization

The inclusion criteria were as follows: (i) patients aged 18–80 years with CKD stage 1–3 (estimated GFR [eGFR] ≥ 30 mL/min/1.73 m²); (ii) those without a recent history of acute illness or hospitalization; and (iii) those with a BP of > 135/85 mmHg or controlled BP with the use of antihypertensive medications. Exclusion criteria were as follows: (i) patients with serious primary diseases affecting major organs, such as the heart, brain, lung, liver, or the hematopoietic system; (ii) those with active cancers and/or other acute infectious diseases; (iii) those that were pregnant; (iv) those that had undergone post-solid organ transplantation; or (v) those with terminal illness.

Eligible patients received an invitation, information regarding the procedure and confidentiality, an informed consent form, and a baseline questionnaire. Eligible patients were randomly assigned to two groups using a computer-based block randomization procedure: (i) low-sodium diet group and (ii) control group. The low-sodium diet group was prescribed a diet containing 1.5 gm/day of salt distributed across three main meals for a duration of three months. The diet was prepared by nutritionists and delivered directly to the patients’ homes. The specific components of this diet are described in Supplementary File 1. The control group, in contrast, continued with their usual diet. Both groups received standard care according to the National Kidney Foundation–Kidney Disease Outcomes Quality Initiative (NKF KDOQI) and Thai CKD guidelines [30]. Throughout the intervention, patients were paired with dietitians and research assistants who conducted dietary recall interviews and provided instructions on the low-salt diet protocol. The dietary history of the control group, which involved collecting information about what type of food was consumed over an extended period of time using open-ended questionnaires, has been favorably compared with other dietary assessment methods, such as food records or 24-hour recall. This method has been comprehensively reviewed with respect to nutrients other than sodium [31]. Diet history was recorded using a food frequency questionnaire (FFQ), which is composed of a list of foods. Patients were asked to identify the frequency of consumption of each food item in broad terms (e.g., per day/per week) [32]. The proportion and estimation of sodium intake, along with other nutrient components, were calculated using the “Immucal” program (Nutrient calculation software V.4.0 database NM2 20219), designed by the Institute of Nutrition, Mahidol University. This software converts the dietary record into proportions of each nutrient.

Measurements and Outcomes Data Acquisition

It is imperative to measure dietary adherence in a dietary intervention trial to ensure that changes in outcomes are attributable to changes in intake. Data were collected at baseline and at every 1 month during the three-month intervention period. Sociodemographic, anthropometric, and medical data were collected at baseline. Biochemical data (complete blood count values; renal function test values; and electrolyte, calcium, and phosphorus levels) were recorded. During each monthly patient visit, BP levels were measured. Urinary sodium excretion was estimated from a 24-hour urine collection at baseline and at 1, 2, and 3 months. Urinary volume, urinary creatinine excretion, and reported urine collection time were used to assess completeness of urine collection, and these are considered by WHO as the gold standard for monitoring adherence [33]. The control group was assessed using a self-reported dietary intake assessment method, as previously described [21]. Diet history is considered a useful method for capturing daily food intake and aligns closest to the dietary assessment methods used in clinical trials. Diet of control group is presented in Supplemental File 2. Blood tests were repeated at the end of the study.

The primary endpoint was the rate of eGFR decline. The secondary endpoint was the effect of the low-salt diet on blood pressure, acid-base status, calcium phosphate balance, and proteinuria.

Sample size calculation

This randomized control trial was designed to determine the effect of low dietary salt on CKD progression by comparing the rate of change in the eGFR between the control and intervention groups. Sample size was calculated using the following formula to test two independent means [34].

$${{n}_{trt}}_{ }=\frac{{\left({Z}_{1-\alpha /2}+{Z}_{1-\beta }\right)}^{2}\left[{{\sigma }_{trt}}^{2}+\frac{{{\sigma }_{con}}^{2}}{r}\right]}{{\varDelta }^{2}}$$

n _trt = Sample size in the intervention group

n _con =Sample size in the intervention group and n_con= r*n_trt

Z _1−α/2 =Standard normal distribution, where α = 0.05, therefore Z_1−α = 1.96

Z1- _β = Standard normal distribution that corresponds to the power of the test at 80%, therefore Z_1−β = 0.842

r = ratio of sample size in the control group to that in the intervention group, where r = n_con / n_trt

$\varDelta$ = The difference between mean of control and intervention group

$$\varDelta ={\mu }_{trt}-{\mu }_{con}$$

µ _trt = Mean number of patients in the intervention group

µ _con = Mean number of patients in the control group

σ ² _trt = Variance in intervention group

σ ² _con = Variance in control group

Based on the study by Ahn S et al. [35], we then calculated the sample size as follows:

n_trt = (1.96 + 0.842)² (4.63² + 3.04²/1)

n_trt = 90

Taking into account a dropout rate of 10%, we aimed to include 200 patients in the trial, with 100 patients in each group.

Statistical Analysis

Descriptive statistics were computed to describe the baseline characteristics of the study population. To investigate the effectiveness of the intervention, continuous variables with a normal distribution are presented as means ± standard deviation (SD). Continuous variables with skewed distribution are presented as median and interquartile range. Categorical variables are presented as frequency and percentage, and they were compared using Pearson’s chi-square or Fisher’s exact test according to the data type. A p value of < 0.05 was considered statistically significant.

The comparison between the rates of CKD progression, which included parameters such as eGFR, blood urea nitrogen, creatinine, 24 hour urine protein, blood pressure, acid-base balance, and calcium-phosphate balance at each time point (before and after intervention), was evaluated using Student’s t-test or Mann–Whitney U test, according to the distribution of variables. The repeated measures analysis of variance (ANOVA), repeated measures analysis of covariance (ANCOVA), generalized estimating equation (GEE), or generalized linear mixed model (GLMM) were used to compare changes in the same patients over the 3-month intervention period according to the distribution of variables. The comparison of serum creatinine increment by ≥ 50% and reduction in eGFR by ≥ 30% between control and intervention groups was calculated by multivariable analysis with Poisson regression, and the results were reported as a risk ratio and risk difference with 95% confidence interval (CI).

IBM SPSS Statistics for Windows version 28.0 (Armonk, NY, USA) was used for analysis.

The study flow is summarized in the CONSORT flow chart in Figure 1.In total, 194 of 254 (76.37.0%) eligible patients provided written informed consent and were included in the primary intention-to-treat analysis. Thereafter, the patients were allocated into the two groups (intervention group, n=99; control group, n=95). During the course of the trial, 19 patients dropped out, leaving 194(91.10%) patients who completed the trial. The baseline characteristics of the participants are presented in Table 1. Briefly, the mean ± SD age of the participants was 61.72 ± 11.47 years in the intervention group (n=99) and 61.00 ± 12.67 years in the control group (n=95). There were no significant differences between the two groups regarding demographic features, mean eGFR, 24-hour urine sodium, and other electrolyte values. The majority of patients were considered to have CKD stage 3 (66.7% in the intervention group and 68.5% in the control group), and one-fourth of the patients in each group has morbid obesity (body mass index [BMI] ≥30 kg/m²).

Effect of dietary sodium restriction on ambulatory BP and other outcomes

The changes in BP are presented in Table 2 and Figure 2. Blood pressure decreased significantly in both groups. Of note, reduction in systolic BP reduction at 3 months was significantly greater in the low-salt group than that in the control group (change from baseline in the intervention group, -6.57, [95%CI: -10.24, -2.89], p <0.001; control group, -0.58, [95%CI: -4.33, 3.17], p =0.072). A median reduction of -2.27/-1.38 mmHg (95% CI: -3.39, -1.14, and -2.15, -0.61, p<0.001) in systolic BP/diastolic BP was achieved in the intervention group and of -0.29/-0.98 mmHg (95% CI: -1.43, 0.86, p=0.626 and -1.76, -0.20, p=0.015) in systolic BP/diastolic BP was observed in the control group. Overall systolic BP reduction in both groups during the 3-month study period was -3.62 (95% CI: -6.70 to -0.54 mmHg, p=0.021).There were no changes in values of heart rate, body weight, and BMI from the baseline values in either group, although body weight had the tendency to decrease in the intervention group (mean change, -0.35 95%; CI: -0.72 to -0.03). The difference in BP changes between the groups was not statistically significant.

Effect of dietary sodium restriction on 24-hour urinary electrolytes

Several significant differences were observed at the end of the intervention period (Table 3).

Mean 24‐hour urinary sodium excretion was 136.12 ± 73.62 mmol/L at baseline in intervention group. At 3 months, reduction in urine sodium excretion was observed in the intervention group, however, it reached statistically significance at month 2 (value at month 2: 120.28 ± 69.34 mmol/L; change from baseline: -14.45 mmol/24 h [95%CI: -27.68 to -1.22], p=0.032), while no significant decrease in urinary sodium excretion was observed in the control group (138.20 ± 70.22 vs. 133.90± 66.50 mmol/L, at baseline and at 3 months, respectively)(Figure 3A).

Overall 24-hour urinary sodium level reduction in both groups during the 3-month study period from baseline was -17.22 mmol/L (95%CI: -31.47 to -2.96, p =0.018). However, this reduction was not significantly different between the groups (-6.60 mmoL/day; 95%CI: -16.30, 3.09, p=0.182). Moreover, there was a significant change in mean 24-hour urinary potassium levels in the control group at month 2 (-4.31 mmol/L, 95% CI: -7.65, -0.97, p= 0.012)(Figure 3 B. No significant differences were detected between the groups for any of the other urine indices.

Effects of dietary sodium restriction on renal progression and proteinuria

Albuminuria and renal function, as measured by the eGFR, at the start of the treatment period, did not change significantly in the intervention group (Tables 3 and 4). The eGFR decreased in both groups at 3 months, and this effect was significantly greater in the control group (Figure 4); eGFR value in the intervention group, 54.26 ± 17.68 mL/min/1.73m² at baseline and 52.77 ± 18.03 mL/min/1.73 m² at 3 months, p=0.086; eGFR value in the control group, 55.28± 17.73 mL/min/1.73m² at baseline and 52.27 ± 15.83 mL/min/1.73 m² at 3 months; p=0.013). The hematocrit decreased significantly in both groups after 3 months. No significant changes in other laboratory data were detected for either treatment, except for serum sodium and chloride levels of the intervention group, which showed significant increase at 3 months, while serum phosphorus levels of the control group showed significant increase at 3 months (Table 4).

This randomized controlled trial examined the effects of an intensive short-term, sodium-restricted, dietary intervention on eGFR and susceptibility to proteinuria—both measures of renal function, blood pressure, and metabolic markers. The following were the key findings:

At 3 months, reduction in systolic BP was significantly greater in the low-salt intervention group than that in the control group.

At 3 months, significant reduction in urine sodium excretion was observed in the intervention group, while no significant decrease in urinary sodium excretion was observed in the control group.

At 3 months, eGFR decreased in both groups, and this effect was significantly greater in the control group.

There is consistent evidence identifying excessive dietary sodium intake as a risk factor for CVD and it impacting CKD progression in patients with CKD. However, there is limited evidence regarding the role of low salt consumption in clinically significant reductions in ESRD, cardiovascular events, and all-cause mortality [36]. We found that a low-sodium dietary intervention resulted in a significant reduction in BP. This is comparable to previous studies that showed that lowering salt intake can induce a significant reduction in blood pressure [37–49].Concomitantly, we found that body weight decreased in the low-sodium group, although the difference was not significant. High salt intake has recently been reported to be positively associated with stomach cancer and obesity. Thus, lower salt intake leads to lower body weight [40]. Various mechanisms have been proposed for salt-dependent hypertension, including volume expansion, modified renal function, disorders in sodium balance, impaired reaction of the RAAS and associated receptors, stimulation of the sympathetic nervous system, and inflammatory processes. The overall effect of a low-salt diet on hypertensive individuals is likely to depend on salt sensitivity, dividing individuals into salt-sensitive and salt-insensitive groups [40]. It is estimated that approximately 50–60% of hypertensive individuals are salt sensitive. In addition to genetic polymorphisms, salt sensitivity increases with age in Black individuals and in persons with metabolic syndrome or obesity. Not every individual reacts to changes in dietary salt intake with alterations in blood pressure, and our group of patients is likely to be in the salt-sensitive category. Although mechanisms of salt-dependent hypertensive effects are increasingly known, more research on measurement, storage and kinetics of sodium, physiological properties, and genetic determinants of salt sensitivity are necessary to solidify the basis for salt reduction recommendations.

Sodium intake can fluctuate considerably on a day-to-day basis, and this study measured 24-hour urinary sodium excretion to reflect sodium intake. However, inherent errors exist in all these methods, including urinary sodium measurement, and the strengths and limitations of each method must be considered. The validity of 24-hour sodium excretion as an accurate estimate of sodium intake for individuals with CKD has not yet been established. Large-scale studies suggest that patients with CKD commonly excrete between 150 and 200 mmol of sodium in their urine over 24 hours [41]. The urinary sodium excretion in our study was comparable to this range (136.12 ± 73.62 mmol/L in intervention group vs. 138.20 ± 70.44 mmol/L in the control group at baseline). The intervention group, which received a salt-restricted diet delivered directly to their homes (three meals per day), showed a greater decrease in urinary sodium compared to the control group, although the difference was not significant. However, it should be highlighted that one limitation of the study is that in the intervention group, patients may have had additional dietary sources contributing to additional salt intake, which could have diminished the effect of salt restriction. The control group also showed a reduction in urinary sodium excretion, possibly due to increased self-awareness while recording the dietary intake, leading to an unintentional reduction in salt intake.

Our study did not show significant changes in proteinuria (mean difference: 034; 95% CI: −27.38 to 28.06). eGFR declined in both groups, which may be attributed to the anticipated progression of CKD. However, the mean change in eGFR from baseline was greater in the control group (mean difference − 3.092, 95%CI: -5.519, -0.665) vs. that in the intervention group (-1.599, 95% CI: -3.310, 0.111), although there were no between-group differences in the final eGFR at follow-up period. Numerous studies have indicated that increased salt consumption is associated with increased albuminuria and the possibility of decreased eGFR [18, 42]. A previous meta-analysis reported no compelling evidence of a reduction in the eGFR decline rate or proteinuria following a low-salt diet [43]. However, pooled analysis in one meta-analysis showed a significant improvement in proteinuria of 0.4 g/day (95% CI: 0.2–0.6 g/day) associated with lower salt intake [18]. Proteinuria and albuminuria have been reported as major risk factors for the progression of type 2 diabetic kidney disease [44, 45]. Therefore, salt restriction through dietary education may be effective in maintaining renal function. Our study showed a tendency for a slow decline in eGFR in the low-salt diet group, but no effect on proteinuria was observed.

Pimenta et al. used total food provision as a means for delivering the low sodium intervention and achieved a mean urinary sodium excretion of 46 ± 27 mmol per day (target 50 mmol/day) [46], indicating closer adherence than that achieved in Dietary Approaches to Stop Hypertension (DASH) [39] with smaller variation between participants. Our study achieved target urinary sodium more than 100 mmoL/day, compatible with CKD subgroups. While these studies provide an indication of the efficacy of sodium restriction in reducing BP in their respective populations, most of the studies lasted for 2–8 weeks, and the daily salt reduction was in the range of 4.3–9.3 g/day. This resulted in a reduction of blood pressure in the range of 3.9–5.9/1.9–3.8 mmHg (systolic/diastolic) in hypertensive individuals and 1.2–2.4/0.3–1.1 mmHg (systolic/diastolic) in normotensive individuals [47]. In our study, the intervention group consumed 1.5 g of sodium per day, whereas the control group consumed an average of 838 mg sodium per day.

Our study has several strengths. For example, multiple nonconsecutive 24-hour urine collections were used to prospectively measure sodium excretion at three time points, which is the gold standard for sodium intake assessment [7]. Another strength of this study is the inclusion of diverse patients, making the results more generalizable to patients with CKD. The intervention group received a highly controlled and standardized dietary intervention with precise control of sodium intake.

The study also had certain limitations. First, sodium intake in the control group was assessed using self-completed frequency food questionnaires (FFQs) and was therefore subject to misreporting and recall bias. Second, different CKD stages may impact urinary sodium excretion. Therefore it is necessary to evaluate the dietary salt intake as a reference value. Third, the patients were assessed for only three months, and we could not conclude whether dietary sodium restriction could slow the progression of kidney disease. Consecutively, a longer study period is warranted to monitor definitive outcomes.

Our findings reveal that dietary reduction in sodium induces clinically relevant reductions in BP, especially systolic BP, among patients with CKD. A low-salt diet helped reduce eGFR decline, although no effect on proteinuria was demonstrated, and no significant differences in other metabolic parameters were found. At month 2, the levels of urinary sodium excretion in patients consuming the low-salt diet were significantly lower than those in patients consuming the normal diet. A short-term low-salt diet resulted in better control of BP and preservation of eGFR. This could offer new insights into dietary interventions for kidney disease management.

Acknowledgements

The authors thank Mr. Anucha Kamsom and Ms. Worachanee Imjaijit for performing the statistical analyses. The authors thank Ms. Khemika Rojtangkom, Ms. Siwaporn Rungrojthanakit, Mr. Peerawit Thinpangnga, and Ms. Monthathip Srisoontorn for preparing the dietary data and for performing the institutional program calculations. The authors extend their gratitude to Ms. Patthanant Srimuang, a nutritionist, for preparing the dietary interventions.

Author Contributions

T.T, W.C, and S.K. designed the study and devised the research plan. S.A, B.M, T.N, S.S, T.T, and S.K. conducted the statistical analysis, research, and data interpretation; drafted the manuscript; and ensured data integrity and accuracy of the analysis. T.T, W.C., and S.K contributed to the discussion and reviewed the manuscript. T.T., Y.H., and H. wrote/edited the original draft and reviewed the manuscript. The final manuscript has been reviewed and approved by all authors.

Data availability

Data generated in this study may downloaded from the ‘figshare’ database https://doi.org/10.6084/m9.figshare.25216343.v1

Funding

We are grateful for the financial support from the Fundamental Fund from Thailand Science Research and Innovation (TSRI) [grant number: 180301/2566].

Conflict of Interest Disclosure

All authors declare that they have no conflicts of interest.

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Table 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

SupplementaryFileLowsalt.docx
Supplementary File 1: Diet of the intervention group
Supplementaryfile2LowSalt.xlsx
Supplementary File 2: Diet of the control group
TableLowSalt.docx

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Effect of low salt diet on progression of chronic kidney disease: A prospective, open-label, randomized controlled trial

Status:

Version 1

Abstract

Figures

INTRODUCTION

METHODS

Participants and Randomization

Measurements and Outcomes Data Acquisition

Sample size calculation

n_trt = (1.96 + 0.842)² (4.63² + 3.04²/1)

n_trt = 90

Statistical Analysis

RESULTS

DISCUSSION

CONCLUSION

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1

Effect of low salt diet on progression of chronic kidney disease: A prospective, open-label, randomized controlled trial

Status:

Version 1

Abstract

Figures

INTRODUCTION

METHODS

Participants and Randomization

Measurements and Outcomes Data Acquisition

Sample size calculation

ntrt = (1.96 + 0.842)2 (4.632 + 3.042/1)

ntrt = 90

Statistical Analysis

RESULTS

DISCUSSION

CONCLUSION

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1

n_trt = (1.96 + 0.842)² (4.63² + 3.04²/1)

n_trt = 90