Lowering Salt Intake in Chronic Kidney Disease: A Pilot Randomized Crossover Trial
Lowering Salt Intake in Chronic Kidney Disease: A Pilot Randomized Crossover Trial
ABSTRACT

 Background:

 It is well recognized that excess dietary salt intake plays a major role in the development
 of hypertension. Chronic Kidney Disease (CKD) is associated with excess salt and water
 retention (excess volume) which is associated with hypertension.

 Hypotheses:

 Hypothesis 1:

 Dietary salt restriction will improve volume status in subjects with CKD stages 3-4 as
 assessed by Bioelectrical Impedance Analysis (BIA).

 Hypothesis 2:

 Dietary salt restriction will result in improved blood pressure control in patients with CKD
 stages 3-4.

 Hypothesis 3:

 Dietary salt restriction will decrease albuminuria in patients with CKD stages 3-4.

 Patients and Trial Design: This randomized crossover pilot study is designed to assess the
 effect of salt restriction on volume status in patients with CKD stages 3 and 4.

 Subjects will be randomized to a treatment order: (1) 4 weeks of salt restriction of <85 mmol
 sodium per day, a 2 week washout period, and 4 weeks of usual salt diet, OR (2) 4 weeks of
 usual diet, 2 weeks washout, and 4 weeks of salt restriction. Patients will receive dietary
 counseling in person at each study visit and at weekly intervals by phone calls from study
 dieticians. At weeks 0, 4, 6 and 10, patients will undergo assessments for (i) physical
 examination with assessments for weight, blood pressure, pulse, anthropometrics and a
 standardized clinical assessment of volume status. (ii) volume status using bioelectrical
 impedance analysis (BIA) (iii) 24-hour urine testing for, albumin, creatinine and aldosterone
 Every 2 weeks throughout the study, a 24-hour urine sodium will be measured for compliance,
 and serum electrolytes will be assessed for safety.

 Data Analysis: BIA measurements in the low salt group will be compared with the regular diet
 group using the standard linear model analysis for 2x2 crossover trials. Additionally,
 24-hour ambulatory and static blood pressure and 24-hour urine aldosterone levels will be
 compared between the two groups.

 Future Implications: A significant reduction in the degree of volume expansion (as assessed
 by BIA) and blood pressure as a result of a salt restricted diet would have implications for
 renal and cardiovascular protection and would warrant confirmation by a larger randomized
 trial.
Inclusion Criteria:

 Individuals eligible to participate in this study must meet all of the following criteria:

 -  Willing and able to provide written, signed informed consent after the nature of the
 study has been explained, and prior to any research-related procedures.

 -  Age ≥ 18 years and ≤ 85 years.

 -  Willing and able to comply with all study procedures.

 -  Patients with eGFR of 20 to 60 ml/min/173m2 by the abbreviated (4-variable) MDRD
 equation and a relatively stable clinical course.

 -  Sitting systolic blood pressure ≥ 100 mmHg prior to study entry (to exclude people at
 risk from hypotension from dietary salt reduction).

 Exclusion Criteria:

 Individuals who meet any of the following exclusion criteria will not be eligible to
 participate in the study:

 -  Recent acute illness (≤1 month). Minor ailments such as a recovered common cold or
 allergic rhinitis would not be considered as exclusion criteria but would be left to
 the site PI's discretion.

 -  Recent hospitalization (≤1 month) unless clearly for a minor elective procedure
 unlikely to interfere with BIA measurements. The final decision will be left to the
 site PI's discretion.

 -  Any psychological condition (including alcoholism) that could interfere with the
 patient's ability to comply with the study protocol.

 -  Subjects with baseline 24-hour urinary sodium excretion ≤100 mmol/day.

 -  Amputation of a limb other than fingers or toes.

 -  Pacemaker, defibrillator, implantable pump, artificial joint, pins, plates or other
 types of metal objects in the body (other than dental fillings).

 -  Coronary stents or metal suture material in the heart.

 -  Use of any investigational product or investigational medical device within 30 days
 prior to screening, or requirement for any investigational agent prior to completion
 of all scheduled study assessments.

 -  Weight over 300 pounds (limitation for examination table).

 -  Pregnancy or lactation.

 -  Patients with kidney diseases known to be associated with salt wasting (see above).

 -  Patients with atrial fibrillation as ambulatory blood pressure measurements may not be
 accurate in this setting.

 -  Any condition that, in the view of the PI, places the subject at high risk of poor
 treatment compliance or of not completing the study.