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.

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.

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.

Paternal Long-Term PM2.5 Exposure Causes Hypertension via Increased Renal AT1R Expression and Function in Male Offspring

Maternal exposure to fine particulate matter (PM2.5) causes hypertension in offspring. However, paternal contribution of PM2.5 exposure to hypertension in offspring remains unknown. In the present study, male Sprague-Dawley rats were treated with PM2.5 suspension for 12 weeks and/or fed with tap water containing an antioxidant tempol. The blood pressure, 24 h-urine volume and sodium excretion were determined in male offspring. The offspring were also administrated with losartan for four weeks. The expressions of AT1R and GRK4 were determined. We found that long-term PM2.5 exposure to paternal rats caused hypertension and impaired urine volume and sodium excretion in male offspring. Both the mRNA and protein expression of GRK4 and its downstream target AT1R were increased in offspring of PM2.5-exposed paternal rats, which was reflected in its function because treatment with losartan, an AT1R antagonist, decreased the blood pressure and increased urine volume and sodium excretion. In addition, the oxidative stress level was increased in PM2.5-treated paternal rats. Administration with tempol in paternal rats restored the increased blood pressure and decreased urine volume and sodium excretion in the offspring of PM2.5-exposed paternal rats. Treatment with tempol in paternal rats also reversed the increased expressions of AT1R and GRK4 in the kidney of their offspring. We suggest that paternal PM2.5 exposure causes hypertension in offspring. The mechanism may be involved that paternal PM2.5 exposure-associated oxidative stress induces the elevated renal GRK4 level, leading to the enhanced AT1R expression and its-mediated sodium retention, consequently causes hypertension in male offspring.

Association of Urinary Sodium Excretion and Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study

BackgroundDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide. Epidemiological evidence of the association between urinary sodium excretion and the presence of DKD in patients with type 2 diabetes mellitus (T2DM) has not yet been well established.MethodsWe performed a cross-sectional study of 1545 patients with T2DM over aged 20 years old from January 2018 to December 2020. Urinary sodium excretion was measured by 24-hour urine samples in inpatients and morning fasting urine samples in outpatients. The associations between urinary sodium excretion and the risks of DKD were examined using stepwise regression analysis, logistic regression analysis and multivariable-adjusted restricted cubic splines (RCS).ResultsRegression analysis showed that urinary sodium was independently associated with urinary albumin to creatinine ratio (UACR) level (P = 0.006) and the risks of DKD (P = 0.042). In multivariable-adjusted RCS analysis, urinary sodium excretion was significantly associated with UACR in all patients (P = 0.008), and exhibited a J-shaped relationship. Logistic regression analysis showed that increased urinary sodium excretion was significantly associated with increased risks of DKD [OR (95% CI); 1.56 (1.07-2.27); P = 0.020]. However, the relationships between urinary sodium excretion and the risks of DKD and albuminuria showed no significance, after further adjustment for HOMA-IR and ba-PWV (brachial-ankle pulse wave velocity) (Both P &gt; 0.05).ConclusionsHigher urinary sodium excretion level was associated with increased risks of DKD among patients with T2DM, dependent of vascular sclerosis and insulin resistance.

Knockout of Macula Densa Neuronal Nitric Oxide Synthase Increases Blood Pressure in db/db Mice

Hypertension is a common comorbid condition in patients with diabetes. The pathogenesis of hypertension in diabetes has not been fully clarified. Primary tubular hyperreabsorption may contribute, which may be counteracted by glomerular hyperfiltration in the early diabetic kidney. In this study, we hypothesize that in early diabetes, the macula densa neuronal nitric oxide synthase (NOS1)-derived nitric oxide (NO) production is enhanced, which blunts tubuloglomerular feedback (TGF) response, promotes glomerular hyperfiltration, and maintains normal blood pressure; conversely, insufficient NO generation by the macula densa induces hypertension by lowering glomerular filtration rate and thus inhibiting natriuresis. To test this hypothesis, we examined the changes of macula densa NOS1 expression and phosphorylation as well as NO production, TGF response, glomerular filtration rate, sodium excretion, and blood pressure in a murine model of leptin receptor-deficient (db/db) diabetes with or without macula densa-specific NOS1 deletion. We found that db/db mice presented reduced fractional renal sodium excretion and only a small increase in blood pressure, associated with upregulated expression and activity of macula densa NOS1, inhibited TGF response, and glomerular hyperfiltration. Genetic knockout of macula densa NOS1 restored the TGF response and attenuated glomerular hyperfiltration in db/db mice but also further reduced fractional renal sodium excretion and substantially increased blood pressure. In conclusion, the present study demonstrates that in the early stage of leptin receptor-deficient diabetes, the upregulation of macula densa NOS1 inhibits TGF and increases glomerular filtration rate, which counteracts renal sodium retention and limits the rise in blood pressure.