Abstract
Background: While low sodium intake (<2.3g/day) is recommended for all, there is uncertainty about feasibility and net cardiovascular effects. In COSTICK, we evaluated the effects of a dietary counselling intervention (reduced sodium intake) on intermediate cardiorenal outcomes in patients with(STICK) and without (COSIP) mild/moderate kidney disease. Methods: This is a protocol for two phase IIb randomised, two-group, parallel, open-label, controlled, single centre trials. Participants were aged >40 years with stable blood pressure, unchanged anti-hypertensive medications, willing to modify diet and provided written informed consent. Participants were excluded for abnormal sodium handling, heart failure, high dose diuretics, immunosuppression, pregnancy/lactation, postural hypotension, cognitive impairment, high or low body mass index (BMI) or inclusion in another trial. STICK participants had estimated glomerular filtration rate (eGFR) 30-60ml/min/1.73m 2 and were excluded for acute kidney Injury, rapidly declining eGFR; known glomerular disease or current use of non-steroidal anti-inflammatory drugs. For COSIP, participants were excluded for known kidney or cardiovascular disease. Participants were randomized to usual care only (healthy eating) or an additional sodium lowering intervention (target <100mmol/day) through specific counseling (sodium use in foods, fresh over processed foods, sodium content of foods and eating outside of home). In STICK the primary outcome is change in 24-hour urinary creatinine clearance. In COSIP, the primary outcome is change in five biomarkers (renin, aldosterone, high sensitivity troponin T, pro-B-type natriuretic peptide and C-reactive protein). Our primary report (COSTICK), reports six biomarker outcome measures in the entire population at 2 years follow-up. Discussion: These Phase II trials will explore uncertainty about low sodium intake and cardiovascular and kidney biomarkers, and help determine the feasibility of low sodium intake. Trial results will also provide preliminary information to guide a future definitive clinical trial, if indicated. Trial registration: STICK: ClinicalTrials.gov NCT02738736 (04/04/2016); COSIP: ClinicalTrials.gov NCT02458248 (15/05/2016).
Highlights
Effective, simple, inexpensive interventions are essential for population-based strategies to impact blood pressure (BP), which may impact the global burden of cardiovascular disease (CVD) and chronic kidney disease (CKD)[1]
There is major uncertainty about whether low sodium intake is associated with more benefit than harm, which needs to be interrogated with clinical trials
The authors state that “These trials will help determine the feasibility of sodium restriction to current guideline levels and determine if this reduction in intake is sustainable.”. This is an important point, supported by the fact that the duration of sodium reduction in RCTs sponsored by the National Heart, Lung and Blood Institute decreased from 36 months (The Hypertension Prevention Trial: Arch Intern Med 1990; 150: 153–162) to 6 months (The Trials of Hypertension Prevention, JAMA 1992; 267: 1213–1220 and Arch Intern Med 1997; 157: 657–667) to 1-month (the Dietary Approaches to Stop Hypertension (DASH) diet N Engl J Med 2001; 344: 3–10)
Summary
In this study protocol of two randomized controlled trials, which intend to investigate the optimal sodium intake in cardiovascular and kidney diseases, the authors correctly state that the evidence supporting low sodium intake (compared to moderate intake, 2.3–4.6g/day) is based on Phase II trials reporting a reduction in BP. It would be helpful to mention this reference, when mentioned the first time in the introduction, i.e. move reference 32 to reference 16 In this context the authors may benefit from consulting two additional references: Kidney International 2018; 93: 921-931 and Kidney International 2018; 93: 776-778, to further explore the known evidence of the association between sodium intake and renal function. Study intervention The diet counselling is more intense in the intervention group, which leaves the question whether there will be other dietary differences between the two groups than differences in sodium intake (Table 2) Such interactions may complicate the final interpretation of the results. The many 24-h urine measurements (Table 3) eliminate one of the previous issues of conflict (the method of sodium intake measurement), which has resulted in reservations on the interpretation of outcomes in previous studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
