Association of Urinary Potassium Excretion with Blood Pressure Variability and Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease.
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ABSTRACT:
SUBMITTER: Suh SH
PROVIDER: S-EPMC8706671 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:WNK1--a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control--is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7 x 10(-3), combined with BRIGHT data-set p = 2 x 10(-4), n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p<10(-7)). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (>10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH.
| S-EPMC2661139 | biostudies-literature
Project description:Many public health policies in Latin America target an optimized sodium and potassium intake. The aims of this study were to assess the sodium and potassium intake using 24-hour urinary analysis and to study their association with blood pressure in a Uruguayan population cohort using cluster analysis. A total of 149 participants (aged 20-85 years) were included in the study, and office blood pressure, anthropometric measurements, biochemical parameters in the blood, and 24-hour urine samples were obtained. The overall mean sodium and potassium excretion was 152.9 ± 57.3 mmol/day (8.9 ± 3.4 g/day of salt) and 55.4 ± 19.6 mmol/day, respectively. The average office systolic/diastolic blood pressure was 124.6 ± 16.7/79.3 ± 9.9 mmHg. Three compact spherical clusters were defined in untreated participants based on predetermined attributes, including blood pressure, age, and sodium and potassium excretion. The major characteristics of the three clusters were (1) high systolic blood pressure and moderate sodium excretion, (2) moderate systolic blood pressure and very high sodium excretion, and (3) low systolic blood pressure and low sodium excretion. Participants in cluster three had systolic blood pressure values that were 23.9 mmHg (95% confidence interval: -29.5 to -1.84) lower than those in cluster one. Participants in cluster two had blood pressure levels similar to those in cluster one (P = 0.32) and worse metabolic profiles than those in cluster one and three (P < 0.05). None of the clusters showed high blood pressure levels and high sodium excretion. No linear association was found between blood pressure and urinary sodium excretion (r < 0.14; P > 0.47). An effect of sodium and potassium intake on blood pressure levels was not found at the population level using regression or cluster analysis.
| S-EPMC6304641 | biostudies-literature
Project description: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.
| S-EPMC4901858 | biostudies-other
Project description:The direction and magnitude of the association between sodium and potassium excretion and blood pressure (BP) may differ depending on the characteristics of the study participant or the intake assessment method. Our objective was to assess the relationship between BP, hypertension and 24-h urinary sodium and potassium excretion among Chinese adults. A total of 1424 provincially representative Chinese residents aged 18 to 69 years participated in a cross-sectional survey in 2017 that included demographic data, physical measurements and 24-h urine collection. In this study, the average 24-h urinary sodium and potassium excretion and sodium-to-potassium ratio were 3811.4 mg/day, 1449.3 mg/day, and 4.9, respectively. After multivariable adjustment, each 1000 mg difference in 24-h urinary sodium excretion was significantly associated with systolic BP (0.64 mm Hg; 95% confidence interval [CI] 0.05-1.24) and diastolic BP (0.45 mm Hg; 95% CI 0.08-0.81), and each 1000 mg difference in 24-h urinary potassium excretion was inversely associated with systolic BP (- 3.07 mm Hg; 95% CI - 4.57 to - 1.57) and diastolic BP (- 0.94 mm Hg; 95% CI - 1.87 to - 0.02). The sodium-to-potassium ratio was significantly associated with systolic BP (0.78 mm Hg; 95% CI 0.42-1.13) and diastolic BP (0.31 mm Hg; 95% CI 0.10-0.53) per 1-unit increase. These associations were mainly driven by the hypertensive group. Those with a sodium intake above about 4900 mg/24 h or with a potassium intake below about 1000 mg/24 h had a higher risk of hypertension. At higher but not lower levels of 24-h urinary sodium excretion, potassium can better blunt the sodium-BP relationship. The adjusted odds ratios (ORs) of hypertension in the highest quartile compared with the lowest quartile of excretion were 0.54 (95% CI 0.35-0.84) for potassium and 1.71 (95% CI 1.16-2.51) for the sodium-to-potassium ratio, while the corresponding OR for sodium was not significant (OR, 1.28; 95% CI 0.83-1.98). Our results showed that the sodium intake was significantly associated with BP among hypertensive patients and the inverse association between potassium intake and BP was stronger and involved a larger fraction of the population, especially those with a potassium intake below 1000 mg/24 h should probably increase their potassium intake.
| S-EPMC7876040 | biostudies-literature
Project description:Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.
| S-EPMC6692500 | biostudies-literature
Project description:Whether hemodialysis patients should be allowed or even encouraged to eat during dialysis remains a controversial topic. This cross-over study aimed to evaluate the impact of feeding during dialysis on intradialytic blood pressure (BP) profile and dialysis adequacy in 26 patients receiving thrice-weekly, in-center hemodialysis. Over three consecutive mid-week dialysis sessions, intradialytic BP was monitored using the Mobil-O-Graph device (IEM, Stolberg, Germany). Blood samples were also obtained for the determination of the urea reduction ratio (URR). At baseline, patients underwent dialysis without the provision of a meal. In phases A and B, a meal with either high-protein (1.5 gr/kg of body weight) or low-protein (0.7 gr/kg of body weight) content was administered 1 h after the initiation of dialysis. The sequence of meals (high-protein and low-protein or vice versa) was randomized. Average intradialytic systolic BP (SBP) was similar on all three occasions. However, compared with baseline, the standard deviation (SD) (11.7 ± 4.1 vs. 15.6 ± 7.6 mmHg, p < 0.01), coefficient of variation (CV) (9.5 ± 3.7% vs. 12.4 ± 6.0%, p < 0.01) and average real variability (ARV) (9.4 ± 3.9 vs. 12.1 ± 5.2 mmHg, p < 0.01) of intradialytic SBP were higher in phase A. Similarly, compared with the baseline evaluation, all three indices of intradialytic SBP variability were higher in phase B (SD: 11.7 ± 4.1 vs. 14.1 ± 4.5 mmHg, p < 0.05; CV: 9.5 ± 3.7% vs. 11.1 ± 3.8%, p < 0.05; ARV: 9.4 ± 3.9 vs. 10.9 ± 3.9 mmHg, p < 0.05). Compared with dialysis without a meal, the consumption of a high-protein or low-protein meal resulted in a lower URR (73.4 ± 4.3% vs. 65.7 ± 10.7%, p < 0.001 in phase A and 73.4 ± 4.3% vs. 67.6 ± 4.3%, p < 0.001 in phase B, respectively). In conclusion, in the present study, feeding during dialysis was associated with higher intradialytic SBP variability and reduced adequacy of the delivered dialysis.
| S-EPMC9002965 | biostudies-literature
Project description:Alcohol consumption is linked to urinary sodium excretion and both of these traits are linked to hypertension and cardiovascular diseases (CVDs). The interplay between alcohol consumption and sodium on hypertension, and cardiovascular diseases (CVDs) is not well-described. Here, we used genetically predicted alcohol consumption and explored the relationships between alcohol consumption, urinary sodium, hypertension, and CVDs.MethodsWe performed a comparative analysis among 295,189 participants from the prospective cohort of the UK Biobank (baseline data collected between 2006 and 2010). We created a genetic risk score (GRS) using 105 published genetic variants in Europeans that were associated with alcohol consumption. We explored the relationships between GRS, alcohol consumption, urinary sodium, blood pressure traits, and incident CVD. We used linear and logistic regression and Cox proportional hazards (PH) models and Mendelian randomization in our analysis.ResultsThe median follow-up time for composite CVD and stroke were 6.1 years and 7.1 years respectively. Our analyses showed that high alcohol consumption is linked to low urinary sodium excretion. Our results showed that high alcohol GRS was associated with high blood pressure and higher risk of stroke and supported an interaction effect between alcohol GRS and urinary sodium on stage 2 hypertension (Pinteraction = 0.03) and CVD (Pinteraction = 0.03), i.e., in the presence of high urinary sodium excretion, the effect of alcohol GRS on blood pressure may be enhanced.ConclusionsOur results show that urinary sodium excretion may offset the risk posed by genetic risk of alcohol consumption.
| S-EPMC9319523 | biostudies-literature
Project description:Systolic blood pressure variability is an independent risk factor for mortality and cardiovascular events. Standard measures of blood pressure predict outcome poorly in haemodialysis patients. We investigated whether systolic blood pressure variability was associated with mortality in incident haemodialysis patients. We performed a longitudinal observational study of patients commencing haemodialysis between 2005 and 2011 in East Anglia, UK, excluding patients with cardiovascular events within 6 months of starting haemodialysis. The main exposure was variability independent of the mean (VIM) of systolic blood pressure from short-gap, pre-dialysis blood pressure readings between 3 and 6 months after commencing haemodialysis, and the outcome was all-cause mortality. Of 203 patients, 37 (18.2%) patients died during a mean follow-up of 2.0 (SD 1.3) years. The age and sex-adjusted hazard ratio (HR) for mortality was 1.09 (95% confidence interval (CI) 1.02-1.17) for a one-unit increase of VIM. This was not altered by adjustment for diabetes, prior cardiovascular disease and mean systolic blood pressure (HR 1.09, 95% CI 1.02-1.16). Patients with VIM of systolic blood pressure above the median were 2.4 (95% CI 1.17-4.74) times more likely to die during follow-up than those below the median. Results were similar for all measures of blood pressure variability and further adjustment for type of dialysis access, use of antihypertensives and absolute or variability of fluid intake did not alter these findings. Diastolic blood pressure variability showed no association with all cause mortality. Our study shows that variability of systolic blood pressure is a strong and independent predictor of all-cause mortality in incident haemodialysis patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management.
| S-EPMC3904871 | biostudies-literature
Project description:Background and objectivesData on whether low or high urinary potassium excretion is associated with poor kidney outcome have been conflicting. The aim of this study was to clarify the association between urinary potassium excretion and CKD progression.Design, setting, participants, & measurementsWe investigated the relationship between lower urinary potassium excretion and CKD progression and compared three urinary potassium indices among 1821 patients from the Korean Cohort Study for Outcome in Patients with CKD. Urinary potassium excretion was determined using spot urinary potassium-to-creatinine ratio, spot urinary potassium concentration, and 24-hour urinary potassium excretion. Patients were categorized into four groups according to quartiles of each urinary potassium excretion metric. The study end point was a composite of a ?50% decrease in eGFR from baseline values and ESKD.ResultsDuring 5326 person-years of follow-up, the primary outcome occurred in 392 (22%) patients. In a multivariable cause-specific hazard model, lower urinary potassium-to-creatinine ratio was associated with higher risk of CKD progression (adjusted hazard ratio, 1.47; 95% confidence interval, 1.01 to 2.12) comparing the lowest quartile with the highest quartile. Sensitivity analyses with other potassium metrics also showed consistent results in 855 patients who completed 24-hour urinary collections: adjusted hazard ratios comparing the lowest quartile with the highest quartile were 3.05 (95% confidence interval, 1.54 to 6.04) for 24-hour urinary potassium excretion, 1.95 (95% confidence interval, 1.05 to 3.62) for spot urinary potassium-to-creatinine ratio, and 3.79 (95% confidence interval, 1.51 to 9.51) for spot urinary potassium concentration.ConclusionsLow urinary potassium excretion is associated with progression of CKD.
| S-EPMC6419276 | biostudies-literature
Project description:This study examined the impact of overweight/obesity on sodium, potassium, and blood pressure associations using the Shandong-Ministry of Health Action on Salt Reduction and Hypertension (SMASH) project baseline survey data. Twenty-four-hour urine samples were collected in 1948 Chinese adults aged 18 to 69 years. The observed associations of sodium, potassium, sodium-potassium ratio, and systolic blood pressure (SBP) were stronger in the overweight/obese population than among those of normal weight. Among overweight/obese respondents, each additional standard deviation (SD) higher of urinary sodium excretion (SD=85 mmol) and potassium excretion (SD=19 mmol) was associated with a 1.31 mm Hg (95% confidence interval, 0.37-2.26) and -1.43 mm Hg (95% confidence interval, -2.23 to -0.63) difference in SBP, and each higher unit in sodium-potassium ratio was associated with a 0.54 mm Hg (95% confidence interval, 0.34-0.75) increase in SBP. The association between sodium, potassium, sodium-potassium ratio, and prevalence of hypertension among overweight/obese patients was similar to that of SBP. Our study indicated that the relationships between BP and both urinary sodium and potassium might be modified by BMI status in Chinese adults.
| S-EPMC8031527 | biostudies-literature