No abstract

The present study evaluated the reliability of equations using spot urine (SU) samples in the estimation of 24-hour urine sodium excretion (24-HUNa). Equations estimating 24-HUNa from SU samples were derived from first-morning SU of 101 participants (52.4 ± 11.1 years, range 24–70 years). Equations developed by us and other investigators were validated with SU samples from a separate group of participants (n = 224, 51.0 ± 10.9 years, range 24–70 years). Linear, quadratic, and cubic equations were derived from first-morning SU samples because these samples had a sodium/creatinine ratio having the highest correlation coefficient for 24-HUNa/creatinine ratio (r = 0.728, p < 0.001). In the validation group, the estimated 24-HUNa showed significant correlations with measured 24-HUNa values. The estimated 24-HUNa by the linear, quadratic, and cubic equations developed from our study were not significantly different from measured 24-HUNa, while estimated 24-HUNa by previously developed equations were significantly different from measured 24-HUNa values. The limits of agreement between measured and estimated 24-HUNa by six equations exceeded 100 mmol/24-hour in the Bland-Altman analysis. All equations showed a tendency of under- or over-estimation of 24-HUNa, depending on the level of measured 24-HUNa. Estimation of 24-HUNa from single SU by equations as tested in the present study was found to be inadequate for the estimation of an individual’s 24-HUNa.

S alt-sensitive hypertension (SSH) is characterized by an increase in blood pressure (BP) in response to sodium load and is associated with an increased risk of cardiovascular events. [1][2][3] Owing to high dietary salt intake and genetic predisposition, salt sensitivity of BP is of particular clinical relevance in Asian populations. [4][5][6][7][8] Considering its pathophysiology, thiazide-type diuretics are the preferred antihypertensive agents for patients with SSH.9-11 However, conditions such as hyponatremia and hypokalemia caused by thiazide-type diuretics often contribute to morbidity and mortality, if left unrecognized. Hence, antihypertensive agents that improve urinary sodium excretion without altering electrolyte concentrations would be a better therapeutic option for patients with SSH. Among multiple pathophysiological mechanisms, a relative deficiency of atrial natriuretic peptide (ANP) is considered to result in sodium retention and a suboptimal vasodilatory response to sodium loading observed in patients with SSH.12-15 The renin-angiotensin-aldosterone system (RAAS) also plays a role in the pathogenesis of SSH by modulating renal sodium reabsorption.16 Therefore, enhancing the activity of natriuretic peptides along with inhibition of the RAAS may be an effective, Abstract-Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, doubleblind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6-and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: −20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulato...