Association Of Urinary Sodium Excretion Research Articles

Urinary Sodium Excretion and Kidney Disease Progression in IgA Nephropathy: A Cohort Study

Introduction: The role of dietary sodium intake in the risk of chronic kidney disease progression remains controversial. This study aimed to evaluate the association of urinary sodium excretion and progression of IgA nephropathy. Methods: We assessed 596 patients with IgA nephropathy, and urinary sodium excretion was measured at the time of kidney biopsy. Cox proportional hazards models and restricted cubic splines were used to assess the association between urinary sodium excretion and kidney disease progression events, defined as 50% eGFR decline or development of kidney failure. Results: After a mean follow-up of 58.9 months, a total of 75 (12.6%) participants of IgA nephropathy reached composite kidney disease progression events. The risk of kidney disease progression events was higher in patients with higher urinary sodium excretion. After adjustment for traditional risk factors, higher levels of ln-transformed urinary sodium excretion was associated with the kidney disease progression events in patients with IgA nephropathy (HR: 2.1; 95% CI: 1.4–3.2). In reference to the first tertile of urinary sodium excretion, hazard ratios were 1.9 (95% CI: 1.0–3.4) for the second tertile and 2.1 (95% CI: 1.1–3.9) for the third tertile. Conclusion: Higher levels of urinary sodium excretion were associated with kidney disease progression events in IgA nephropathy independent of clinical and biopsy characteristics.

Sodium Intake and Incident Atrial Fibrillation in Individuals With Vascular Disease

Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality. To study the association between sodium intake and incident atrial fibrillation (AF). This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024. Estimated sodium intake from a morning fasting urine sample (Kawasaki formula). The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines. A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed (P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake. In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P<0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P<0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P<0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P<0.001). Stronger associations with glaucoma (P interaction=0.001) were noted in participants with a higher glaucoma polygenic risk score. Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The association of urinary sodium excretion with dietary sodium intake among selected low-income urban households.

The association of urinary sodium excretion with dietary sodium intake among selected low-income urban households.

Association between urinary sodium excretion and hard outcomes in non-dialysis chronic kidney disease patients

BackgroundRestriction of sodium intake is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains uncertain. We evaluated the association between urinary sodium excretion (as a surrogate for sodium intake) with the occurrence of renal failure and mortality in patients with non-dialytic CKD.MethodsWe conducted a retrospective study of patients followed at a CKD clinic care hospital from October 2006 to March 2017. Adult patients with non-dialytic CKD were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a categorical variable (categorized as quintiles: 1st quintile: 0.54–2.51 g; 2nd quintile: 2.52–3.11 g, 3rd quintile: 3.12–3.97 g, 4th quintile: 3.98–5.24 g and 5th quintile: 5.26–13.80 g) and the outcomes of interest. The primary outcome was defined as progression to end-stage renal disease requiring any type of renal replacement therapy. The secondary outcome was mortality.ResultsTwo hundred five patients were included in the study (mean follow up of 2.6 years) with a mean eGFR of 26 (19–41) ml/min/1.73m2. 37 patients (18%) required renal replacement therapy and 52 (25,3%) died. There was association between urinary sodium excretion and need for renal replacement therapy (adjusted HR 0.245; 95%CI 0.660–0.912). There was no association between urinary sodium excretion and mortality in adjusted models.ConclusionModerate sodium intake was associated with a lower risk of renal failure.

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 > 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.

Association of Urinary Sodium Excretion and Left Ventricular Hypertrophy in People With Type 2 Diabetes Mellitus: A Cross-Sectional Study

BackgroundIt has been well documented that left ventricular hypertrophy (LVH) is highly associated with the incidence of cardiovascular disease (CVD). Evidence indicated that high sodium intake was closely related with LVH in general population. However, information is not available regarding the association between urinary sodium excretion and LVH in patients with type 2 diabetes mellitus (T2DM). This study aimed to explore the association between urinary sodium excretion and LVH in patients with T2DM.MethodsThis cross-sectional analysis included baseline data from 1,556 individuals with T2DM enrolled in the NanFang Prospective Diabetes Study (NFPDS). Urinary sodium excretion levels were measured from 24-hour urine samples of inpatients and morning fasting urine samples of outpatients. Left ventricular dimensions were assessed by echocardiography. The associations between urinary sodium excretion and the risks of cardiovascular events, LVH and left ventricular mass index (LVMI) were examined using linear regression analysis, logistic regression and restricted cubic splines (RCS).ResultsUrinary sodium excretion levels were positively associated with cardiometabolic risk factors, including systolic blood pressure, body mass index, waist circumference and LVMI (All P<0.001). Odds ratios of the highest quartile of urinary sodium excretion compared with the lowest quartile were 1.80 (95% CI, 1.28-2.54; P=0.001) for LVH and 1.77 (95% CI, 1.06-2.94; P=0.028) for CVD, after adjusted for demographics, lifestyle risk factors and cardiovascular risk factors. Multivariable-adjusted RCS analysis of the association between urinary sodium excretion and LVMI showed a significant association (P=0.001) and lacked evidence of a nonlinear association (P=0.406).ConclusionThis study indicated that high urinary sodium excretion was independently associated with increased risk of LVH and CVD in patients with T2DM, suggesting that control of sodium intake may be valuable for the prevention of diabetic cardiovascular complications.

Associations of urinary sodium excretion with central hemodynamics and changes in vascular structure and function at high altitude.

Research reports on associations of urinary sodium excretion with central hemodynamic parameters and vascular changes are quite limited in general or non‐hypertensive population. The purpose of the current study was to explore such associations in Chinese general Tibetans living at high altitude. This cross‐sectional study was conducted in Luhuo County, Ganzi Tibetan Autonomous Prefecture with average elevation of 3800 meters from December 2018 to January 2019. A total of 294 Tibetans were included in the current study. Twenty‐four hour urinary sodium excretion was estimated by second fasting spot urine in the morning using Kawasaki formula. Central hemodynamic parameters, including central systolic blood pressure (CSBP), central diastolic blood pressure (CDBP), central pulse pressure (CPP), central mean arterial pressure (CMAP), augmentation pressure (AP), and augmentation index standardized for heart rate of 75 (AIx75), were evaluated using the SphygmoCor system. Vascular structures and functions were assessed by carotid intima media thickness (CIMT) test and brachial ankle pulse wave velocity (baPWV), respectively. Estimated mean 24h urinary sodium excretion of Tibetans in Luhuo County was 5.26±1.61 g. After adjustment, estimated 24h urinary sodium was positively associated with CSBP (β = 1.15, p = .008) and CPP (β = 0.87, p = .013). Line graph of means across urinary sodium quartiles showed that associations of 24 h urinary sodium excretion with AIx75 and baPWV presented approximate “J” shape after controlling for confounders. Estimated 24 h sodium excretion was independently and positively associated with CSBP and CPP. Moreover, association between urinary sodium excretion and arterial elasticity, as evaluated by baPWV and AIx75, presented “J” shape. Further studies are needed to verify J‐shaped association and “safe” zone of sodium intake.

Association of urinary sodium excretion with fluid overload in patients with chronic kidney disease

Objective: To investigate the relationship between urinary sodium excretion and fluid overload (FO) in non-dialysis patients with chronic kidney disease (CKD). Methods: Patients with CKD stage 1-4 who underwent bioelectrical impedance (BIA) in the Department of Nephrology, Jiangsu Province Hospital from December 2019 to January 2021 were recruited. All enrolled patients were categorized into two groups according to whether or not they develop FO. Further, clinical parameters were compared between the two groups. Spearman correlation analysis was used to investigate the association between over hydration/extracellular water (OH/ECW) and clinical characteristics. Multivariate logistic regression analysis was performed to evaluate the relationship between urinary sodium excretion and FO (FO was defined as OH/ECW≥7%). Results: A total of 385 patients with CKD stage 1-4 were finally included in the study, with a mean age of (46±15) years. There were 216 male cases (56.1%), and 150 cases (39.0%) existed FO. Spearman correlation analysis indicated that OH/ECW positively correlated with urinary sodium excretion (r=0.147, P=0.004), urinary protein excretion (r=0.555, P<0.001) and systolic blood pressure (r=0.241, P<0.001), but inversely related to estimated glomerular filtration rate (eGFR) (r=-0.111, P=0.030) and serum albumin (r=-0.659, P<0.001). After adjusting for confounding factors including age, systolic blood pressure, diabetes, urinary protein excretion, serum albumin, serum sodium, serum chlorine, urinary calcium excretion, urinary phosphorus excretion and use of diuretics, multivariate logistic regression analysis demonstrated that higher level of urinary sodium excretion was associated with increased risk of FO in patients with CKD (OR=1.005, 95%CI: 1.000-1.011, P=0.048). Conclusion: High urinary sodium excretion is independently associated with fluid FO in non-dialysis patients with CKD.

Association of Sodium with Obstructive Sleep Apnea. The ELSA-Brasil Study.

Rationale: Excessive sodium may have a role in the pathogenesis of obstructive sleep apnea (OSA) for patients with hypervolemic conditions, but it is unclear whether this is valid for all patients with OSA, including those with no significant comorbidities.Objectives: To test the association of urinary sodium and OSA in a large sample of participants from the ELSA-Brasil (Estudo Longitudinal de Saúde do Adulto-Brasil) Study. In addition, we stratified the analysis participants according to the presence of hypertension.Methods: In this cross-sectional study, OSA was defined by an apnea-hypopnea index ≥15 events/h. A validated 12-hour urine collection as representative of the 24-hour period was obtained from all participants to measure sodium excretion. We performed a logistic regression analysis to test the association of urinary sodium excretion with OSA (dependent variable) adjusting for age, sex, race and income, glomerular filtration rate, diabetes, physical activity, and antihypertensive classes related to sodium excretion. To address potential residual factors that may influence sodium excretion, we performed additional analysis replacing sodium excretion for salt intake (food frequency questionnaire) using the same models.Results: We studied 1,946 participants (age 49 ± 8 yr; 43.4% men). A third of them had OSA. Compared with those with no OSA, participants with OSA presented with higher sodium excretion (1.66 [1.19-2.29] vs. 1.99 [1.44-2.69] g/12 h; P < 0.001). After adjustments for confounding factors, we found no overall significant associations of sodium excretion with OSA (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.97-1.23; P = 0.150). Regardless of the OSA status, the sodium excretion was higher in hypertensive than in normotensive participants (1.93 [1.35-2.64] vs. 1.71 [1.22-2.37] g/12 h). An independent association of sodium excretion with OSA was observed in patients with hypertension only (OR, 1.326; 95% CI, 1.067-1.648; P = 0.011), but the interaction of urinary sodium with hypertension was not significant (P = 0.37). The analysis of salt intake revealed consistent findings.Conclusions: The potential role of sodium in the pathogenesis of OSA seems to be modest and limited for those with higher salt intake and, consequently, higher fluid retention such as observed in patients with hypertension.

Association of Urinary Sodium Excretion with Vascular Damage: A Local Kidney Effect, Rather Than a Marker of Generalized Vascular Impairment.

Evidence suggests that increased salt consumption induces blood pressure- (BP) mediated organ damage, yet it remains unclear whether it reflects a generalized micro- and macrovascular malfunction independent of BP. We studied 197 newly diagnosed and never-treated individuals with hypertension, intermediate hypertensive phenotypes, and normal BP, classified by use of 24-hour ambulatory BP monitoring. Sodium excretion and microalbuminuria were estimated in 24-hour urine samples, dermal capillary density was estimated from capillaroscopy, and arterial stiffness was estimated with pulse wave velocity (PWV) and augmentation index (AIx). Sodium excretion correlated with microalbuminuria (p<0.001) and 24-hour and day- and nighttime systolic BP, but not with office blood pressure, arterial stiffness, or capillary density. In the multivariate analysis, the association with microalbuminuria was maintained (p=0.007). In a population free from the long-standing effects of hypertension, increased salt intake appears to be associated with early signs of vascular kidney damage, rather than a diffuse micro- and macrovascular impairment.

Association of Low Urinary Sodium Excretion With Increased Risk of Stroke

The positive relationship between sodium intake and blood pressure is well established. However, results of observational studies on dietary sodium intake and risk of stroke are inconsistent. Moreover, prospective studies with multiple 24-hour urine samples for accurate estimation of habitual sodium intake are scarce. We examined the association of urinary sodium excretion (UNaV) as an accurate estimate of intake with risk of stroke. We studied 7330 individuals free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort of Dutch men and women. The UNaV was measured in two 24-hour urine specimens at baseline (1997-1998) and two specimens during follow-up (2001-2003). Baseline median UNaV was 137 mmol/24 h (interquartile range, 106-171 mmol/24 h). During a median follow-up of 12.5 years (interquartile range, 11.9-12.9 years), a total of 183 stroke events occurred. An inverse association between UNaV and risk of stroke was observed after adjustment for age and sex (hazard ratio [HR] per 1-SD [51 mmol/24 h] decrement, 1.36; 95% CI, 1.11-1.65), which remained independent of additional adjustment for anthropometric, dietary, lifestyle, and other potential confounding factors (HR, 1.44; 95% CI, 1.14-1.82). After adjustment for potential mediators (systolic blood pressure and antihypertensive medication, plasma renin, aldosterone, and sodium levels), the association of UNaV with risk of stroke remained unchanged, with HRs (95% CIs) of 1.44 (1.14-1.82), 1.50 (1.18-1.90), 1.54 (1.21-1.97), and 1.49 (1.17-1.90), respectively. This prospective study revealed an association of low UNaV with an increased risk of stroke.

Association of urinary sodium excretion with blood pressure and risk factors associated with hypertension among Cameroonian pygmies and bantus: a cross-sectional study

BackgroundHigh salt intake increases blood pressure (BP) and hypertension risk. This study aimed to examine association of urinary sodium excretion with BP and hypertension correlates among Cameroonian pygmies under hunter-gatherer subsistence mode and Bantus, living in urban area under unhealthy behavioral habits.MethodsIn this cross-sectional cluster sampling study, we randomly enrolled rural pygmies living in Lolodorf and urban Bantus living in Douala. The World Health Organization steps questionnaire was used to collect socio-demographic and lifestyle data. Height, weight, BP and single overnight spot urine samples were obtained in all participants. BP was measured in triplicate. Urinary sodium and potassium excretion was determined by flame photometry. Data were recorded and analyzed using SPSS 16.0.ResultsWe included 150 Pygmies and 150 Bantus aged 38 ± 12 years and 33 ± 11 years, respectively (p < 0.0001). Compare to Bantus, pygmy’s height and weight were respectively: 1.54 ± 0.09 m vs 1.72 ± 0.12 m; and 54.4 ± 9.2 kg vs 77.2 ± 14.8 kg, all p < 0.0001. Age-standardized prevalence of hypertension was 3.3% among Pygmies and 28% among Bantus (p < 0.0001). Age-adjusted systolic and diastolic BP were lower in Pygmies than in Bantus (107 ± 12 vs 119 ± 17 mmHg and 71 ± 11 vs 78 ± 13 mmHg respectively, all P < 0.0001). BP increased with age but to a lesser extent in Pygmies (all p < 0.01). Urinary sodium excretion was lower in Pygmies than in Bantus (46.9 ± 32.4 vs 121.5 ± 61.0 mmol/l, p < 0.0001). Systolic and diastolic BP were positively associated with urinary sodium excretion in Bantus (all p < 0.05). In the two groups, urinary potassium excretion was similar, and was not related to blood pressure. In the total study group and in Bantus taken separately, urinary sodium excretion was higher in hypertensive than in normotensive subjects. Multivariable logistic regression showed that urinary sodium excretion, Bantu status and age emerged as independent determinants of hypertension in the whole study group (OR (95%CI): 1.012 (1.005–1.018); 11.408 (3.599–36.165); 1.095 (1.057–1.135) respectively, p < 0.0001).ConclusionHunter-gatherer pygmies exhibit low level of urinary sodium excretion related to low rate of hypertension and slower BP increase with age. Salt intake was a major driver of hypertension in our study population. Our findings highlight the need of efforts to implement nationwide prevention programs promoting risk factor screening and healthier lifestyles including reduction of dietary salt intake in Cameroonian.

The association of urinary sodium excretion and the need for renal replacement therapy in advanced chronic kidney disease: a cohort study

BackgroundRestriction of dietary sodium is routinely recommended for patients with chronic kidney disease (CKD). Whether or not sodium intake is associated with the progression of CKD and mortality remains controversial. We evaluated the association of urinary sodium excretion (as a surrogate for sodium intake) on the need for renal replacement therapy and mortality in patients with advanced CKD.MethodsWe conducted a retrospective study of patients followed at a CKD clinic of a tertiary care hospital from January 2010 to December 2012. Adult patients with advanced CKD (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2) were included. Using a time-to-event analysis, we examined the association of urinary sodium excretion as a continuous and also as a categorical variable (categorized as low sodium diet - LSD (<100 mEq/day), medium sodium diet - MSD (100–150 mEq/day), and high sodium diet - HSD (>150 mEq/day) and the outcomes of interest. The primary outcome was defined as composite of progression to end-stage renal disease requiring any type of renal replacement therapy and mortality. The secondary outcome was change in eGFR/year.Results341 patients (82 LSD, 116 MSD and 143 HSD) were included in the study (mean follow up of 1.5 years) with a mean eGFR decline of 2.7 ml/min/1.73 m2/year. 105 patients (31 %) required renal replacement therapy and 10 (3 %) died. There was no association between urinary sodium excretion and change in the eGFR or need for renal replacement therapy and mortality in crude or adjusted models (unadjusted HR 1.002; 95%CI 1.000–1.004, adjusted HR 1.001; 95%CI 0.998–1.004).ConclusionIn patients with advanced CKD (eGFR < 30 ml/min/1.73 m2), sodium intake does not appear to impact the progression of CKD to end-stage renal disease; however, more definitive studies are needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0338-z) contains supplementary material, which is available to authorized users.

PT077 Association of Urinary Sodium Excretion With Blood Pressure and Cardiovascular Clinical Events in 17,033 Latin Americans

PT077 Association of Urinary Sodium Excretion With Blood Pressure and Cardiovascular Clinical Events in 17,033 Latin Americans

Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies

Several studies reported a U-shaped association between urinary sodium excretion and cardiovascular disease events and mortality. Whether these associations vary between those individuals with and without hypertension is uncertain. We aimed to explore whether the association between sodium intake and cardiovascular disease events and all-cause mortality is modified by hypertension status. In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure. Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009). Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets. Full funding sources listed at end of paper (see Acknowledgments).

Association of Urinary Sodium Excretion With Insulin Resistance in Korean Adolescents: Results From the Korea National Health and Nutrition Examination Survey 2009-2010.

High sodium intake is a well-known risk factor for elevated blood pressure and is responsible for a higher incidence of cardiovascular events. Reports have suggested an association of sodium intake with insulin resistance (IR) and type 2 diabetes mellitus in adults. However, evidence on an association between sodium intake assessed on the basis of urinary sodium excretion and IR in adolescents is scarce. The present study aimed at investigating the association between urinary sodium excretion and IR among South Korean adolescents.This population-based, cross-sectional study analyzed the data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) 2009 to 2010. The data of a total of 1353 adolescents (779 boys and 574 girls) were included in the final analysis. Spot urine samples were collected, and urinary sodium excretion was estimated by using the urinary sodium concentration (U[Na+]), U[Na+] to urinary creatinine ratio (U[Na+]/Cr), and U[Na+] to specific gravity unit (SGU) ratio (U[Na+]/SGU). IR was assessed by using the homeostasis model assessment of IR (HOMA-IR). Hierarchical multivariable logistic regression analysis was performed to assess the risk for a high HOMA-IR according to urinary sodium excretion.The mean levels of U[Na+], U[Na+]/Cr, and U[Na+]/SGU were significantly higher in subjects in the highest HOMA-IR quartile (Q4) than in subjects in the lowest, second, or third quartiles (Q1–3) of HOMA-IR. The mean values of HOMA-IR and several cardiometabolic parameters tended to progressively increase with the U[Na+], U[Na+]/Cr, and U[Na+]/SGU quartiles. Q3 of U[Na+] was at a significantly higher risk than Q1 of U[Na+] of an association with Q4 of HOMA-IR, after adjustment for confounding variables. Q3 and Q4 of U[Na+]/Cr and U[Na+]/SGU, respectively, had significantly higher risks, than the respective Q1s, of an association with Q4 of HOMA-IR. The risk of an association with Q4 of HOMA-IR demonstrated significantly increasing trends with increasing quartiles of U[Na+], U[Na+]/Cr, and U[Na+]/SGU irrespective of confounding factors.Urinary sodium excretion was positively associated with IR in South Korean adolescents. The monitoring and control of urinary sodium excretion may be recommended as an important intervention for the prevention of IR and related diseases in adolescents.

Association of Urinary Sodium Excretion With Blood Pressure and Cardiovascular Clinical Events in 17,033 Latin Americans.

Information on actual sodium intake and its relationships with blood pressure (BP) and clinical events in South America is limited. The aim of this cohort study was to assess the relationship of sodium intake with BP, cardiovascular (CV) events, and mortality in South America. We studied 17,033 individuals, aged 35-70 years, from 4 South American countries (Argentina, Brazil, Chile, and Colombia). Measures of sodium excretion, estimated from morning fasting urine, were used as a surrogate for daily sodium intake. We measured BP and monitored the composite outcome of death and major CV events. Overall mean sodium excretion was 4.70±1.43g/day. A positive, nonuniform association between sodium and BP was detected, with a significant steeper slope for the relationship at higher sodium excretion levels (P < 0.001 for interaction). With a median follow-up of 4.7 years, the primary composite outcome (all-cause death, myocardial infarction, stroke, or heart failure) occurred in 568 participants (3.4%). Compared with sodium excretion of 5-6g/day (reference group), participants who excreted >7g/day had increased risks of the primary outcome (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.24 to 2.40; P < 0.001), as well as death from any cause (OR 1.87; 95% CI 1.23 to 2.83; P = 0.003) and major CV disease (OR 1.77; 95% CI 1.12 to 2.81; P = 0.014). Sodium excretion of <3g/day was associated with a statistically nonsignificant increased risk of the primary outcome (OR 1.20; 95% CI 0.86 to 1.65; P = 0.26) and death from any cause (OR 1.25; 95% CI 0.81 to 1.93; P = 0.29), and a significant increased risk of major CV disease (OR 1.50; 95% CI 1.01 to 2.24; P = 0.048), as compared to the reference group. Our results support a positive, nonuniform association between estimated urinary sodium excretion and BP, and a possible J-shaped pattern of association between sodium excretion over the entire range and clinical outcomes.

PS11 - 2. Higher urinary sodium excretion is weakly associated with albuminuria, but not with retinopathy in type 1 diabetes: the EURODIAB Study

Nutritional advice that favourably affects cardiovascular risk factors, such as blood pressure (BP), may also have a favourable effect on microvascular complications. Restriction of salt intake is known to reduce BP. We studied the association of urinary sodium excretion, as a marker of salt intake, with the prevalence of microalbuminuria, macroalbuminuria, non-proliferative and proliferative retinopathy in individuals with type 1 diabetes (T1DM).

Blood Pressure in Relation to Interactions Between Sodium Dietary Intake and Renal Handling

There is abundant evidence that sodium intake is related to blood pressure. However, the relationship varies between individuals and is probably determined by renal sodium handling. We investigated clinic and ambulatory blood pressure in relation to interactions between sodium dietary intake and renal handling, as assessed by 24-hour urinary sodium excretion and endogenous lithium clearance, respectively. We calculated fractional excretion of lithium and fractional distal reabsorption rate of sodium, as markers of proximal and distal sodium handling, respectively. The 766 subjects included 379 men and 478 ambulatory hypertensive patients. They were never treated (n=697) or did not take antihypertensive medication for ≥2 weeks (n=69). In adjusted analyses, none of the associations of urinary sodium excretion, fractional excretion of lithium, and fractional distal reabsorption rate of sodium with clinic or ambulatory blood pressure were statistically significant (P≥0.09). However, there was significant (P=0.01) interaction between urinary sodium excretion and fractional excretion of lithium in relation to nighttime diastolic blood pressure. In tertile 3 but not tertiles 1 and 2 of fractional excretion of lithium, nighttime diastolic pressure was positively associated with urinary sodium excretion (P=0.03). However, nighttime diastolic pressure was higher in tertile 1 than tertile 3 of fractional excretion of lithium (+2.0 mm Hg; P=0.01), especially in the bottom tertile of urinary sodium excretion (+4.9 mm Hg; P<0.001). Similar trends were observed for nighttime systolic pressure and clinic and 24-hour diastolic pressure. In conclusion, sodium dietary intake and proximal tubular handling interact to be associated with blood pressure.