BACKGROUND: Diuretic resistance is a relevant clinical issue in acute heart failure (AHF), but a standardized, quantitative definition is still missing. The aim of this analysis was to highlight discrepancies between previously proposed definitions of diuretic response and to propose a new urinary sodium (NaU)-based definition of diuretic efficiency (DE) to identify diuretic resistant (DR) patients.
METHODS: Three historical definitions of diuretic response and a new NaU-based DE definition, evaluating total NaU after the first diuretic bolus per 40 mg furosemide administered, were applied in a retrospective analysis to an AHF population treated with intravenous (i.v.) loop diuretics. Baseline characteristics, in-hospital clinical data and outcomes at discharge and mid-term follow-up were collected and compared among DR and non-DR patients for each definition.
RESULTS: Among 53 patients, 39 (73.6%), 51 (96.2%) and 3 (5.7%) were DR according to weight-derived, diuresis-derived, and spot NaU definition, respectively. The median value of the new NaU-based definition was 31 mmol/40 mg and patients were stratified accordingly. DR patients showed lower cumulative diuresis (5200 mL, 3300-6700 vs 9825, mL 6200-12,200, p = 0.007) and weight loss (4 kg, 1-5 vs 6 kg, 3-8.5, p = 0.023), higher BNP levels (808, 443-1037 vs 351, 209-859, p = 0.062) at the conclusion of protocol-guided i.v diuretic therapy, which was less frequently stopped due to decongestion in DR as compared to non-DR patients (57.7 vs 85.2%, p = 0.026). Six-months mortality or HF hospitalizations were more frequent in DR patients (OR 18.6, 95% CI 2.1-161.2, p = 0.008).
CONCLUSIONS: The NaU-based DE definition might solve discrepancies of other previously proposed definitions.

OBJECTIVE: Spot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF.
METHODS: This observational and ambispective study included 1145 outpatients with chronic HF followed in a single center specialized HF clinic. UNa+ assessment was carried out 1-5 days before each visit. The endpoints of the study were the association between UNa+ and risk of a) long-term death and b) AHF-hospitalization and total WHF events (including AHF-hospitalization, emergency department visits or parenteral loop-diuretic administration in HF clinic), assessed by multivariate Cox and negative binomial regressions.
RESULTS: The mean±standard deviation of age was 73±11 years, 670 (58.5%) were men, 902 (78.8%) were on stable NYHA class II, and 595 (52%) had LFEF ≥50%. The median (interquartile range) UNa+ was 72 (51-94) mmol/L. Over a median follow-up of 2.63 (1.70-3.36) years, there were 293 (25.6%) deaths and 382 WHF events (244 AHF-admissions) in 233 (20.3%) patients. After multivariate adjustment, baseline UNa+ was inverse and linearly associated with the risk of total WHF (IRR, 1.07; 95%CI, 1.02-1.12; P=.007) and AHF-admissions (IRR, 1.08; 95%CI, 1.02-1.14; P=.012) and borderline associated with all-cause mortality (HR, 1.04; 95%CI, 0.99-1.09; P=.068).
CONCLUSIONS: In outpatients with chronic HF, lower UNa+ was associated with a higher risk of recurrent WHF events.

BACKGROUND: Several studies reported that exposure to higher levels of fine particulate matter (PM2.5) was associated with deteriorated lipid profiles in children and adolescents. However, whether a sodium-rich diet could modify the associations remains unknown. We aimed to examine the associations of long-term exposure to PM2.5 with blood lipids in children and adolescents, and further examine the effect modification by dietary and urinary sodium levels based on a multi-community population in China.
METHODS: The 3711 study participants were from a cross-sectional study, which interviewed children and adolescents aged 6 to 17 years across Sichuan Province, China between 2015 and 2017. Blood lipid outcomes including blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were assessed. Information on daily dietary sodium consumption was estimated with a semi-quantitative food frequency questionnaire (FFQ), and urinary sodium was used as an internal exposure biomarker. A linear regression model was applied to estimate the associations of prior 2-years\' average exposure to ambient PM2.5 with blood lipids. The effect modification by dietary and urinary sodium was examined by stratified analyses.
RESULTS: The participants from rural areas had higher levels of daily sodium consumptions. The results of multivariable regression analysis indicated that per 10 μg/m3 incremental change in PM2.5 was associated with a 1.56% (95% confidence interval 0.90%-2.23%) and a 2.26% (1.15%-3.38%) higher blood TC and LDL-C levels, respectively. Among the study participants with higher levels of dietary sodium or urinary sodium, exposure to higher levels of PM2.5 was significantly associated with deteriorated lipid profiles. For example, each 10 μg/m3 incremental change in exposure to PM2.5 was correlated with a 2.83 (-4.65 to -0.97) lower percentage decrease in blood HDL-C levels among the participants who were from the highest quartile of urinary sodium levels. While, these associations changed to be nonsignificant in the participants who were from the lowest quartile of dietary sodium levels.
CONCLUSIONS: Exposure to higher levels of PM2.5 was associated with deteriorated blood lipid levels in children and adolescents. It is noteworthy that these associations might be ameliorated through the adoption of a low-sodium dietary regimen.

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear.
METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer\'s disease, and vascular dementia from multiple sources.
RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer\'s disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g.
CONCLUSIONS: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples.
CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) study, published in August of 2023, was the first randomized clinical trial to compare natriuresis-guided decongestion (based on spot urinary sodium measurement) to standard of care in patients with acute heart failure with congestion receiving loop diuretic therapy. Based on results from their trial, the authors concluded that natriuresis-guided loop diuretic treatment was safe and improved natriuresis and diuresis without impacting long-term clinical outcomes. The original PUSH-AHF trial included limited information about renal outcomes and left clinicians with important questions about how natriuresis-guided decongestion might affect their patients\' renal function. On May 12, 2024, however, at the 2024 Annual Congress of the HFA-ESC, Dr. Kevin Damman provided an in-depth exploration of renal outcomes from the trial when he presented a pre-specified, secondary analysis, renal function in the PUSH-AHF trial. This review puts the sub-study findings into context by considering the history of the original trial from which they came from and explaining the need for a close study of its renal outcomes particularly. It highlights the potential impact of renal function in PUSH-AHF on clinical practice and future directions that should be considered by the cardiology research community.

OBJECTIVE: 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.
METHODS: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study.
METHODS: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data.
METHODS: 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.
METHODS: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

BACKGROUND: Spot urinary sodium concentration (UNa) is advocated in guidelines to assess diuretic response and titrate dosage in acute heart failure (AHF). However, no randomised controlled trial data exists to support this approach. We performed a prospective pilot trial to investigate the feasibility of this approach.
METHODS: 60 patients with AHF (n = 30 in each arm) were randomly assigned to titration of loop diuretics for the first 48 hours of admission according to UNa levels (intervention arm) or based on clinical signs and symptoms of congestion (standard care arm). Diuretic insufficiency was defined as UNa < 50 mmol/L. Endpoints relating to diuretic efficacy, safety and AHF outcomes were evaluated.
RESULTS: UNa-guided therapy patients experienced less acute kidney injury (20% vs 50%, p = 0.01) and a tendency towards less hypokalaemia (serum K+<3.5 mmol, 7% vs 27%, p = 0.04), with greater weight loss (3.3 kg vs 2.1 kg, p = 0.01). They reported a greater reduction in the clinical congestion score (-4.7 vs -2.6, p < 0.01) and were more likely to report marked symptom improvement (40% vs 13.3%, p = 0.04) at 48 hours. There was no difference in the length of hospital stay (median LOS: 8 days in both groups, p = 0.98), 30-day mortality or readmission rate.
CONCLUSIONS: UNa-guided titration of diuretic therapy in AHF is feasible and safer than titration based on clinical signs and symptoms of congestion, with more effective decongestion at 48 hours. Further large-scale trials are needed to determine if the superiority of this approach translates into improved patient outcomes.

Heart failure (HF) is the common final pathway of several conditions and is characterized by hyperactivation of numerous neurohumoral pathways. Cardiorenal interaction plays an essential role in the progression of the disease, and the use of diuretics is a cornerstone in the treatment of hypervolemic patients, especially in acute decompensated HF (ADHF). The management of congestion is complex and, to avoid misinterpretations and errors, one must understand the interface between the heart and the kidneys in ADHF. Congestion itself may impair renal function and must be treated aggressively. Transitory elevations in serum creatinine during decongestion is not associated with worse outcomes and diuretics should be maintained in patients with clear hypervolemia. Monitoring urinary sodium after diuretic administration seems to improve the response to diuretics as it allows for adjustments in doses and a personalized approach. Adequate assessment of volemia and the introduction and titration of guideline-directed medical therapy are mandatory before discharge. An early visit after discharge is highly recommended, to assess for residual congestion and thus avoid readmissions.

UNASSIGNED: Excess dietary salt consumption is a major contributor to hypertension and cardiovascular disease. Public education programs on the dangers of high salt intake, and population level interventions to reduce the salt content in foods are possible strategies to address this problem. In Jamaica, there are limited data on the levels of salt consumption and the population\'s knowledge and practices with regards to salt consumption. This study therefore aims to obtain baseline data on salt consumption, salt content in foods sold in restaurants, and evaluate knowledge, attitudes, and practices of Jamaicans regarding salt consumption.
UNASSIGNED: The study is divided into four components. Component 1 will be a secondary analysis of data on urinary sodium from spot urine samples collected as part of a national survey, the Jamaica Health and Lifestyle Survey 2016-2017. Component 2 will be a survey of chain and non-chain restaurants in Jamaica, to estimate the sodium content of foods sold in restaurants. Component 3 is another national survey, this time on a sample 1,200 individuals to obtain data on knowledge, attitudes and practices regarding salt consumption and estimation of urinary sodium excretion. Component 4 is a validation study to assess the level of agreement between spot urine sodium estimates and 24-hour urinary sodium from 120 individuals from Component 3.
UNASSIGNED: This study will provide important baseline data on salt consumption in Jamaica and will fulfil the first components of the World Health Organization SHAKE Technical Package for Salt Reduction. The findings will serve as a guide to Jamaica\'s Ministry of Health and Wellness in the development of a national salt reduction program. Findings will also inform interventions to promote individual and population level sodium reduction strategies as the country seeks to achieve the national target of a 30% reduction in salt consumption by 2025.

Urinary sodium was indicated to be associated with dyslipidemia, but inconsistent conclusions for this association exist across the present observational studies.
This study aimed to evaluate the causal association between urinary sodium and circulating lipid levels [low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein cholesterol (HDL-C)] through Mendelian randomization.
Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) with pleiotropy-resistant methods were performed. Data for urinary sodium were obtained from the genome-wide association study (GWAS) from 446,237 European individuals. Data for lipid profiles were extracted from GWAS based on the UK Biobank (for the discovery analysis) and the Global Lipids Genetics Consortium (for the replication analysis).
In the discovery analysis, UVMR provided evidence that per 1-unit log-transformed genetically increased urinary sodium was associated with a lower level of HDL-C level (beta = -0.32; 95% CI: -0.43, -0.20; p = 7.25E-08), but not with LDL-C and triglycerides. This effect was still significant in the further MVMR when considering the effect of BMI or the other two lipid contents. In contrast, higher genetically predicted triglycerides could increase urinary sodium in both UVMR (beta = 0.030; 95% CI: 0.020, -0.039; p = 2.12E-10) and MVMR analyses (beta = 0.029; 95% CI: 0.019, 0.037; p = 8.13E-10). Similar results between triglycerides and urinary sodium were found in the replication analysis.
Increased urinary sodium may have weak causal effects on decreased circulating HDL-C levels. Furthermore, genetically higher triglyceride levels may have independent causal effects on increased urinary sodium excretion.