Accurate Estimation of Sodium Intake with Limited Patient Burden

High sodium (Na+) intake is associated with worse cardiovascular and renal
outcomes, whereas the contrary is observed when potassium (K+) rich diets are
consumed. Because of this, patients with kidney and cardiovascular disease are
advised to limit Na+ intake to 2 g/d. To monitor Na+ intake, patients collect
24-hour urine in which Na+ excretion is measured. This method is based on the
assumption that 24-hour Na+ excretion equals 24-hour Na+ intake. Recent studies
demonstrated that this assumption is false and that Na+ can be stored in and
released from a newly discovered skin compartment. The use of 24-hour K+
excretion for estimation of K+ intake, although not commonly used, has also
shown to be inaccurate. As a result, dietary advices to patients based on
24-hour urine collections are inadequate. We need improved urine-based methods
for estimation of dietary Na+ and K+ intake, preferably with limited patient
burden.

The primary aim of this study is to assess whether repetitive morning, daytime
or pre-night spot urine sampling can accurately estimate dietary Na+ intake and
to determine the number of spot urine collections that are needed. We will
assess whether using repetitive spot urine collection is superior to using a
single 24-hour urine collection in estimating dietary Na+ intake. We will also
explore this approach for K+ intake. The secondary objective is to define
whether the dietary Na+/K+ ratio can be more accurately predicted than dietary
Na+ or K+ intake separately, by measuring the urinary Na+/K+ ratio. If so, we
will determine the number of spot and 24-hour urine collections that are needed
for accurate estimation of the dietary Na+/K+ ratio. Further, we will assess
whether Na+ or K+ intake estimation by 24-hour urine collection can be improved
when Na+ or K+ excretion is corrected for aldosterone and cortisol excretion.

We will compare the abovementioned objectives between healthy participants and
patients with chronic kidney disease, because Na+ measurements in the latter
group can be influenced by medication use, kidney function and albuminuria.

This is an observational study. All study participants will receive a 14-day
standardized diet, which will serve as a control for Na+ and K+ intake,
containing a fixed amount of Na+ (157 mmol/day = 3600 mg/day) and K+ (85
mmol/day = 3300 mg/day).

Participants will need to collect all urine for 17 days and will follow a
14-day study diet Participants are urged to not conduct strenuous exercise
during the study. They will be instructed to keep daily documentation of
consumed foods, beverages and diuresis. They will need to attend one 60-minute
screening visit, three 30-minute study visits and four 15-minute study visits
at our research facility. If desired, we will perform four home visits to
replace the 15-minute study visits to lower the study burden. They will undergo
a 10 mL blood draw twice.

Study insights will contribute to increased accuracy of urine-based Na+ and K+
intake estimation methods and may reduce patient burden. This will allow for
better dietary advice on Na+ intake reduction, which will improve
cardiovascular and renal outcomes. Using data from this study, we will develop
a guideline on Na+ intake estimation in clinical practice.