Lack of Validation of a Same-Day Outpatient Protocol for Determination of Salt Sensitivity of Blood Pressure

Salt sensitivity of blood pressure has been studied in humans with a 48-hour inpatient protocol of salt loading and depletion or with longer outpatient protocols using high- and low-salt diets. Results have been reproducible, but both methods are laborious and costly. A 6-hour protocol of intravenous salt loading and furosemide has been reported but never validated. We studied 14 normal volunteers (39±2 years old; 86% women and 21% black) with the inpatient and 6-hour protocols, separated by 30 days. Four subjects (29%) were salt sensitive in the inpatient protocol. They had higher systolic blood pressure, higher body mass index, and somewhat lower plasma renin activity than salt-resistant subjects. Baseline systolic blood pressure before both protocols was highly reproducible (r=0.90; P<0.0001; limits of agreement: +6.2 to -8.0 mm Hg), whereas the response to salt depletion was not (r=0.09). Three salt-sensitive and 4 salt-resistant subjects were misclassified by the short protocol. Three-hour natriuresis by furosemide in the short protocol (344±15 mmol) was not different from the 12-hour natriuresis in the inpatient protocol (357±19). However, stimulation of plasma renin activity and aldosterone was significantly less in the short (+0.10±0.07 ngA(I)/L/sec and -61±44 pmol/L) than in the inpatient protocol (+1.80±0.60 ngA(I)/L/sec and +256±88 pmol/L; P<0.03 for both). Activation of hormonal changes that regulate depressor responses to salt depletion may not have occurred with the 3-hour natriuresis of the short protocol. This methodology cannot be used to study salt sensitivity of blood pressure, because the phenotype, mechanisms, and prognosis of the latter have been defined with the inpatient protocol.