The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study): protocol of a randomized trial

Abstract

BackgroundDespite evidence implicating dietary sodium in the pathogenesis of cardiovascular disease (CVD) in chronic kidney disease (CKD), quality intervention trials in CKD patients are lacking. This study aims to investigate the effect of reducing sodium intake on blood pressure, risk factors for progression of CKD and other cardiovascular risk factors in CKD.Methods/designThe LowSALT CKD study is a six week randomized-crossover trial assessing the effect of a moderate (180 mmol/day) compared with a low (60 mmol/day) sodium intake on cardiovascular risk factors and risk factors for kidney function decline in mild-moderate CKD (stage III-IV). The primary outcome of interest is 24-hour ambulatory blood pressure, with secondary outcomes including arterial stiffness (pulse wave velocity), proteinuria and fluid status. The randomized crossover trial (Phase 1) is supported by an ancillary trial (Phase 2) of longitudinal-observational design to assess the longer term effectiveness of sodium restriction. Phase 2 will continue measurement of outcomes as per Phase 1, with the addition of patient-centered outcomes, such as dietary adherence to sodium restriction (degree of adherence and barriers/enablers), quality of life and taste assessment.DiscussionThe LowSALT CKD study is an investigator-initiated study specifically designed to assess the proof-of-concept and efficacy of sodium restriction in patients with established CKD. Phase 2 will assess the longer term effectiveness of sodium restriction in the same participants, enhancing the translation of Phase 1 results into practice. This trial will provide much-needed insight into sodium restriction as a treatment option to reduce risk of CVD and CKD progression in CKD patients.Trial registrationUniversal Trial Number: U1111-1125-2149. Australian New Zealand Clinical Trials Registry Number: ACTRN12611001097932

A Randomized Trial of Dietary Sodium Restriction in CKD

“…Phase 2 of this study will entail follow-up to 6 months and will assess long-term effects of sodium restriction on the outcomes presented in this article as well as assessment of dietary compliance to determine the translation of benefits outside of the clinical trial setting. 39 The difference between weight and BMI between those who completed and those who withdrew from the study may have affected the study results; however, reasons for attrition were not related to the treatment but rather to the intensity of the data collection schedule and to medical reasons unrelated to the study. Although the small sample size may have limited the generalizability of the results to other CKD populations, it was sufficient to afford an observed power of 80%.…”

“…A detailed description of the LowSALT CKD study was published elsewhere. 39 Trial registration numbers for the LowSALT CKD study are as follows: Universal Trial Number U1111-1125-2149, and Australian New Zealand Clinical Trials Registry Number ACTRN12611001097932.…”

Cafeteria Diet Increases Liquid Intake and Serum Creatinine Levels in Rats

“…The obesity model applied in this study contains high sodium content that exceeds the limits recommended by the guidelines 21 . High sodium intake is associated with the development of cardiovascular diseases including hypertension 22,23 . The association between sodium intake and thirst is well established.…”

Sodium Intake and Blood Pressure in Patients with Chronic Kidney Disease: A Salty Relationship

“…Several factors contribute to the development of CVD in this population, mostly related to previous comorbidities such as hypertension and diabetes mellitus. However, other risk factors are peculiar to CKD, namely, anemia, bone mineral disorders and (particularly relevant to this review) the inability to excrete the amount of sodium needed and consequent fluid overload [9]. Indeed, dietary sodium intake has been associated with numerous modifiable risk factors for CVD in CKD patients, including increased BP, volume overload, left ventricular hypertrophy, inflammation and endothelial damage [10-12].…”

“…Excess sodium in chronic kidney disease (CKD) is caused by decreased sodium excretion and high sodium intake (partially mediated by taste sensitivity). This increases cardiovascular risk not only via altered increments in extracellular volume and BP but also through the direct toxic effects of sodium in blood vessels (adapted from McMahon et al [9]).…”