Estimation of sodium consumption by novel formulas derived from random spot and 12-hour urine collection

The gold standard for estimating sodium intake is 24h urine sodium excretion. Several equations have been used to estimate 24h urine sodium excretion, however, a validated formula for calculating 24h urine sodium excretion from 12h urine collection has not yet been established. This study aims to develop novel equations for estimating 24h urine sodium excretion from 12h and random spot urine collection and also to validate existing spot urine equations in the Thai population. A cross-sectional survey was carried out among 209 adult hospital personnel. Participants were asked to perform a 12h daytime, 12h nighttime, and a random spot urine collection over a period of 24 hours. The mean 24h urine sodium excretion was 4,055±1,712 mg/day. Estimated urine sodium excretion from 3 different equations using random spot urine collection showed moderate correlation and agreement with actual 24h urine sodium excretion (r = 0.54, P<0.001, ICC = 0.53 for Kawasaki; r = 0.57, P<0.001, ICC = 0.44 for Tanaka; r = 0.60, P<0.001, ICC = 0.45 for INTERSALT). Novel equations for predicting 24h urine sodium excretion were then developed using variables derived from 12h daytime urine collection, 12h nighttime urine collection, random spot urine collection, 12h daytime with random spot urine collection, and 12h nighttime with random spot urine collection which showed strong correlation and agreement with actual measured values (r = 0.88, P<0.001, ICC = 0.87; r = 0.83, P<0.001, ICC = 0.81; r = 0.67, P<0.001, ICC = 0.62; r = 0.90, P<0.001, ICC = 0.90; and r = 0.83, p<0.001, ICC = 0.82 respectively). Bland-Altman plots indicated good agreement between predicted values and actual 24h urine sodium excretion using the new equations. Newly derived equations from 12h daytime and 12h nighttime urine collection with or without casual spot urine collection were able to accurately predict 24h urine sodium excretion.

Roles of sodium-glucose cotransporter 2 of mesangial cells in diabetic kidney disease

We have been studying the presence of sodium-glucose cotransporter 2 (SGLT2) in mesangial cells and pericytes since 1992. Recent large placebo-controlled studies of SGLT2 inhibitors in patients with type 2 diabetes mellitus have reported desirable effects of the inhibitors on the diabetic kidney and the diabetic heart. Most studies have indicated that these effects of SGLT2 inhibitors could be mediated by the tubuloglomerular feedback (TGF) system. However, a recent study about urine sodium excretion in the presence of an SGLT2 inhibitor did not show any increases in urine sodium excretion. A very small dose of an SGLT2 inhibitor did not inhibit SGLT2 at the S1 segment of proximal tubules. Moreover, SGLT2 inhibition protects against progression in chronic kidney disease with and without type 2 diabetes. In these circumstances, the TGF hypothesis involves several theoretical concerns that must be clarified. The presence of SGLT2 in mesangial cells seems to be very important for diabetic nephropathy. We now propose a novel mechanism by which the desirable effects of SGLT2 inhibitors on diabetic nephropathy are derived from the direct effect on SGLT2 expressed in mesangial cells.

Spot Urine Formulas to Estimate 24-Hour Urinary Sodium Excretion Alter the Dietary Sodium and Blood Pressure Relationship

We evaluated the relationship between estimated 24-hour urinary sodium excretion from the Kawasaki, Tanaka, and INTERSALT (International Study of Sodium, Potassium, and Blood Pressure) formulas and blood pressure (BP). We pooled 10 034 person-visit data from 3 cohort studies in Bangladesh that had measured 24-hour urine sodium (m-24hUNa), potassium, creatinine excretion, and BP. We used m-24hUNa, potassium, and creatinine where necessary, rather than spot urine values in the formulas. Bland-Altman plots were used to determine the bias associated with formula-estimated sodium relative to m-24hUNa. We compared the sodium excretion and BP relationships from m-24hUNa versus formula-estimated sodium excretions, using restricted cubic spline plots for adjusted multilevel linear models. All formulas overestimated 24-hour sodium at lower levels but underestimated 24-hour sodium at higher levels. There was a linear relationship between m-24hUNa excretion and systolic BP, while estimated sodium excretion from all 3 formulas had a J-shaped relationship with systolic BP. The relationships between urine sodium excretion and diastolic BP were more complex but were also altered by using formulas. All formulas had associations with BP when a sex-specific constant sodium concentration was inserted in place of measured sodium. Since we used the m-24hUNa, potassium, and creatinine concentrations in formulas, the J-shaped relationships are due to intrinsic problems in the formulas, not due to spot urine sampling. Formula-estimated 24-hour urine sodium excretion should not be used to examine the relationship between sodium excretion and BP since they alter the real associations.

P0151SEXUAL DIMORPHISM IN HYPERTENSION ACCORDING TO THE CHANGE OF URINE SODIUM AND VOLUME EXCRETION BY SEX OR MENOPAUSE

Background and Aims A recent study demonstrated female rats more rapidly excreted urine sodium and water under saline bolus infusion than male rats, and suggested sexual dimorphisms in renal transporters. However, the sexual differences in renal salt and water excretion was not yet investigated with human data. We purposed to clarify whether the sexual difference of natriuretic and diuretic ability exists, and it contributes to decreasing blood pressure (BP) in nondiabetic chronic kidney disease (CKD) patients. Method This is a secondary analysis of an open-label, randomized, controlled study determining the effect of intensive low-salt diet education on BP and albuminuria in nondiabetic CKD patients. A total of 235 patients had stopped all renin-angiotensin blocking agents or diuretics during a run-in period for eight weeks (0w). After the run-in period, they received olmesartan (40mg daily) for eight weeks (8w), and then maintained the same medicine with low-salt diet education for an additional eight weeks (16w). Results Mean age of premenopausal women (n=50), same-aged young men (n=76), postmenopausal women (n=68), and same-aged older men (n=41) was 40.7, 40.2, 59.0, and 69.9 years old, respectively. Their MDRD eGFR was 76.2, 71.6, 59.8, and 58.8 mL/min/1.73m2, respectively. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was lower in premenopausal women (129/79 mmHg) than in young men (134/83 mmHg). Daily salt intake decreased in 16w in premenopausal women (1839 → 1288mg, p=0.008) and young men (2494 → 1552mg, p=0.001) compared with them in 0w, while there was no significant change in postmenopausal women (2443 → 2171mg, p=0.610) and older men (2870 → 2366mg, p=0.458). Except for the premenopausal women (136 (0w) → 133 (16w) mEq/day, p=0.749), urine sodium excretion for 24 hours significantly decreased in 16w compared with that in 0w or 8w (young men: 154 (8w) → 137 (16w)mEq/day p=0.042, postmenopausal women: 152 (0w) → 128m (16w)Eq/day p=0.016, older men: 181 (0w) → 145 (16w)mEq/day p=0.019). Also, urine volume was significantly larger in the premenopausal women than in young men in 8w and 16w (8w: 1009 vs. 980mL p=0.002, 16w: 1004 vs. 978mL, p=0.006), while it was not different between postmenopausal women and older men (8w: 1002 vs. 990 p=0.347, 16w: 1003 vs. 1001 p=0.895). The urine volume was positively correlated with BP in the premenopausal women, while it was negatively associated with BP in young men in 16w. Conclusion Although sodium intake was similarly decreased in premenopausal women and young men, urine sodium excretion did not fall, and urine volume increased in premenopausal women. This phenomenon disappeared in postmenopausal women. Augmented natriuretic and diuretic potency might contribute to lower BP in premenopausal women with nondiabetic CKD.