Cardiorenal Effects of Long‐Term Phosphodiesterase V Inhibition in Pre–Heart Failure

Background Phosphodiesterase V (PDEV) is upregulated in heart failure, leading to increased degradation of cGMP and impaired natriuresis. PDEV inhibition improves the renal response to B‐type natriuretic peptide in animal models. We tested the hypothesis that long‐term PDEV inhibition would improve renal function and cardiorenal response after short‐term volume load in subjects with pre–heart failure. Methods and Results A total of 20 subjects with pre–heart failure (defined as an ejection fraction ≤45% without previous diagnosis of heart failure) and renal impairment were randomized in a 2:1 manner to tadalafil or placebo. Baseline echocardiography and renal clearance study were performed, followed by a short‐term saline load and repeated echocardiography and renal clearance study. Subjects then received either tadalafil at a goal dose of 20 mg daily or placebo, and the study day was repeated after 12 weeks. Long‐term tadalafil did not improve glomerular filtration rate (median increase of 2.0 mL/min in the tadalafil group versus 13.5 mL/min in the placebo group; P =0.54). There was no difference in urinary sodium or cGMP excretion with PDEV inhibition following short‐term saline loading. Conclusions Glomerular filtration rate and urinary sodium/cGMP excretion were not significantly different after 12 weeks of tadalafil compared with placebo. These results do not support the use of PDEV inhibition to improve renal response in patients with pre–heart failure. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01970176.

Estimated 24 Hour Urinary Sodium and Potassium Excretion in a Population of Moroccan Adults

Background: Excessive sodium (Na) intake and low potassium (K) intake are associated with adverse cardiovascular health outcomes. Morocco lacks data on actual Na and K intake in adults. The aim of this study was to estimate the mean intake of Na and K in a Moroccan population of adults using the 24-h urinary excretion and to examine their association with blood pressure (BP). Methods: A total of 371 adults, who participated in the urinary validation sub-study of the STEP-wise Survey-Morocco-2017-2018, have complete data on demographic, anthropometric and blood pressure and have provided a valid 24-h urine collection according to the standard protocol of the World Health Organization (WHO). Results: The mean 24-h urinary sodium excretion was 2794 mg (SD, 1394) and the median was 2550 mg (IQR, 1780-3726). The mean 24-h urinary potassium excretion was 1898 mg (SD, 1044) and the median was 1640 mg (IQR, 1170-2410). Sodium excretion was between 3000 and 5000 mg/day in 31% of participants, < 3000 mg/day in 64%, and > 5000 mg/day in only 5%. No significant association of urinary sodium or potassium with blood pressure was found. Conclusion: Sodium intake in the studied population of Moroccan adults was higher than WHO recommendation and was comparable to levels reported in countries from Eastern Mediterranean Region. The vast majority of participants had a sodium intake < 5000 mg/day, with only 5% were above this level. Potassium intake was in the range of 1000 to 3000 mg/day. Within these ranges, there was no association between sodium or potassium intake and blood pressure. This information is crucial to help implement the national strategy to reduce sodium intake as a cost-effective intervention to prevent chronic disease in Morocco.

Urinary Sodium Excretion and Adherence to the Mediterranean Diet in Older Adults

Despite the well-known benefits of the Mediterranean Diet (MedDiet), data on the sodium intake is scarce. This study aimed to quantify the association between sodium excretion and the adherence to the MedDiet in the elderly. A representative sample of 1500 Portuguese adults (≥65 years) was assessed (1321 were eligible for the present analysis). A 24 h urine sample was collected and analysed for creatinine and sodium. Excessive sodium intake was defined as above 2000 mg/day. The adherence to the MedDiet was assessed by the PREDIMED. A binary logistic regression model was conducted to evaluate the association between urinary sodium excretion and the adherence to the MedDiet. Odds Ratios (OR) and respective 95% Confidence Intervals (95% CI) were calculated. Excessive sodium excretion was observed in 80.0% of men and 91.5% of women whereas a high adherence to the MedDiet was reported by 42.2% of women and 46.4% of men. After adjusting for confounders, excessive sodium excretion was associated with a high adherence to the MedDiet in men (OR = 1.94; 95% CI: 1.03–3.65) but not in women. These results show that the MedDiet can be an important source of sodium and highlight the need for implementing strategies to reduce sodium intake when following a MedDiet.

Urinary sodium excretion is not associated with the incidence of end-stage kidney disease and kidney-related death: results from the UK Biobank

Background: Sodium reduction lowers blood pressure and albuminuria, indicating a hypothesized but yet-to-be proven association between sodium intake and kidney-related endpoints. Objectives: We aimed to investigate the associations of 24-h urinary sodium excretion, reflecting daily sodium intake, with kidney-related outcomes. Methods: Prospective cohort of 444,086 middle- to early late-aged participants from the UK Biobank. The primary outcome was a composite of incident end-stage kidney disease (ESKD) and death due to a kidney-related cause, each of which was separately examined as a secondary outcome. Death due to a non-kidney related cause prior to ESKD was considered a competing event. Results: The mean 24-h urinary sodium excretion estimated from spot urinary biomarkers was 3.3 g. During a median follow-up of 11.8 years, 1,256 composite events occurred. Multivariable-adjusted cause-specific hazards models showed that, with every 1-g increment in 24-h urinary sodium excretion, hazard ratios (95% confidence intervals) were 1.03 (0.91-1.16), 1.08 (0.88-1.32), and 1.01 (0.88-1.16) for the composite outcome, incident ESKD, and kidney-related death, respectively. Similar null results were observed when the exposure was treated as binary (<2 g/d vs. ≥2 g/d) or multicategorical (quartiles). Nonlinear associations were not detected with restricted cubic splines. The findings also held constant in prespecified sensitivity and subgroup analyses. Conclusions: Estimated 24-h urinary sodium excretion was not linearly or nonlinearly associated with the incidence of ESKD or death due to kidney-related causes. Our findings did not support the hypothesized notion that sodium intake should be reduced to prevent kidney-related endpoints at the population level.

Validity of predictive equations for 24-h urinary sodium excretion at the population and individual levels among Chinese adults aged 18–69 years

Spot urine (SU) collection is a convenient method commonly used for sodium estimation, but its validity in predicting 24-h urinary sodium (24-hUNa) excretion has not been thoroughly evaluated among the general population. The aim of this study was to comprehensively assess the validity of eight existing methods in predicting 24-hUNa excretion by using SU samples among Chinese adults. We analyzed 1424 representative individuals aged 18 to 69 years. We compared the measured and estimated measurements of 24-hUNa at the population level by examining bias, the correlation, intraclass correlation coefficients (ICCs), receiver operating characteristic (ROC) curves and Bland–Altman plots and analyzed the relative and absolute differences and misclassification at the individual level. The bias for all methods was significant (all p < 0.001), among which the smallest bias was − 7.9 mmol for the Toft formula and the largest bias was − 53.8 mmol for the Mage formula. Correlation coefficients were all less than 0.380, all formulas exhibited an area under the ROC curve below 0.683, and the Bland–Altman plots indicated slightly high dispersion of the estimation biases at higher sodium levels regardless of the formula. The proportions of relative differences > 40% for the eight methods were all over one-third, the proportions of absolute differences > 51.3 mmol/24 h (3 g/day NaCl) were all over 40%, and the misclassification rates (7, 10, and 13 g/day NaCl as cutoff points) were all over 65%. Caution remains due to poor validity between estimated and actual measurements when using the eight formulas to obtain a plausible estimation for surveillance of the Chinese population sodium excretion, and the results do not support the application of SU to estimate sodium intake at the individual level due to its poor performance with respect to classification.

Association between 24 h Urinary Sodium and Potassium Excretion and Dietary Intake in Japanese Male Adolescent Football Players

High urinary sodium-to-potassium ratio is considered a strong risk factor for hypertension. This study aimed to evaluate urinary excretion of sodium and potassium, and we analyzed these levels associated with dietary intake in Japanese adolescent football players. This cross-sectional study included 120 Japanese male adolescent football players. Over 24 h, urine was collected and measured for creatinine, sodium, and potassium levels. A dietary assessment was performed using a self-administered diet history questionnaire. The study analyzed 79 participants. The mean urinary sodium was 143.2 mmol/day, urinary potassium was 42.8 mmol/day, and the mean urinary sodium-to-potassium ratio was 3.6. Compared with the Japanese Dietary Reference Intakes, the estimated salt intake was 73.4% for the participants who exceeded the sodium intake, and the estimated potassium intake was 73.4% for the participants who did not satisfy it. Multiple regression analysis revealed that milk and dairy product intake was independently and positively associated with urinary potassium (β = 0.252) and independently and negatively associated with the urinary sodium-to-potassium ratio (β = −0.254). Adolescent football players had a high-sodium and low-potassium diet, well above the Japanese Dietary Reference Intakes recommendations. Milk and dairy products could be effective for increasing urinary potassium and decreasing the urinary sodium-to-potassium ratio.