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1.  Alcohol and blood pressure: the INTERSALT study. 
BMJ : British Medical Journal  1994;308(6939):1263-1267.
OBJECTIVES--To assess the relation between alcohol intake and blood pressure in men and women and in men at younger and older ages; to examine the influence of amount and pattern of alcohol consumption, as well as of acute effects, taking into account body mass index, smoking, and urinary sodium and potassium excretion. DESIGN--Subjects reported alcohol consumption for each of seven days before standardised blood pressure measurement, and whether they had consumed any alcohol in the 24 hours before measurement. SETTING--50 centres worldwide. SUBJECTS--4844 men and 4837 women aged 20-59. MAIN OUTCOME MEASURES--Effect of alcohol on blood pressure estimated by taking a weighted average of regression coefficients from centres. Acute effect assessed by examining mean differences in blood pressure of non-drinkers and of heavy drinkers who had and had not consumed alcohol in the 24 hours before measurement. Effect of pattern of consumption assessed by examining mean differences in blood pressure of non-drinkers compared with drinkers (i) whose intake was concentrated in fewer days or who were drinking more frequently, and (ii) whose alcohol intake varied little over the seven days or varied more substantially, as indicated by the standard deviation of daily consumption. RESULTS--Of the 48 centres in which some people reported consuming at least 300 ml/week of alcohol, 35 had positive regression coefficients linking heavy alcohol consumption to blood pressure. Overall, alcohol consumption was associated with blood pressure, significantly at the highest intake. After account was taken of key confounders, men who drank 300-499 ml alcohol/week had systolic/diastolic blood pressure on average 2.7/1.6 mmHg higher than non-drinkers, and men who drank > or = 500 ml alcohol/week had pressures of 4.6/3.0 mmHg higher. For women, heavy drinkers (> or = 300 ml/week) had blood pressures higher by 3.9/3.1 mmHg than non-drinkers. Heavy drinking and blood pressure were strongly associated in both sexes, and in men at both younger (20-39 years) and older (40-59 years) ages. In men who were heavy drinkers, episodic drinkers (those with great variation in daily alcohol consumption) had greater differences in blood pressure compared with non-drinkers than did regular drinkers of relatively constant amounts. CONCLUSION--The significant relation of heavy drinking (3-4 or more drinks/day) to blood pressure, observed in both men and women, and in younger and older men, was independent of and added to the effect on blood pressure of body mass index and urinary excretion of sodium and potassium. The findings indicate the usefulness of targeting those at high risk as well as the general population to reduce the adverse effects of alcohol on blood pressure.
PMCID: PMC2540174  PMID: 7802765
2.  Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. 
BMJ : British Medical Journal  1988;297(6644):319-328.
The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.
PMCID: PMC1834069  PMID: 3416162
3.  Lower potassium intake is associated with increased wave reflection in young healthy adults 
Nutrition Journal  2014;13:39.
Background
Increased potassium intake has been shown to lower blood pressure (BP) even in the presence of high sodium consumption however the role of dietary potassium on vascular function has received less attention. The aim of this study was to evaluate the relationship between habitual intake of sodium (Na) and potassium (K) and measures of arterial stiffness and wave reflection.
Methods
Thirty-six young healthy adults (21 M, 15 F; 24 ± 0.6 yrs; systolic BP 117 ± 2; diastolic BP 63 ± 1 mmHg) recorded their dietary intake for 3 days and collected their urine for 24 hours on the 3rd day. Carotid-femoral pulse wave velocity (PWV) and the synthesis of a central aortic pressure waveform (by radial artery applanation tonometry and generalized transfer function) were performed. Aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform.
Results
Subjects consumed an average of 2244 kcals, 3763 mg Na, and 2876 mg of K. Average urinary K excretion was 67 ± 5.3 mmol/24 hr, Na excretion was 157 ± 11 mmol/24 hr and the average Na/K excretion ratio was 2.7 ± 0.2. An inverse relationship between AI and K excretion was found (r = -0.323; p < 0.05). A positive relationship between AI and the Na/K excretion ratio was seen (r = 0.318; p < 0.05) while no relationship was noted with Na excretion alone (r = 0.071; p > 0.05). Reflection magnitude, the ratio of reflected and forward waves, was significantly associated with the Na/K excretion ratio (r = 0.365; p <0.05) but not Na or K alone. PWV did not correlate with Na or the Na/K excretion ratio (p > 0.05) but showed an inverse relationship with K excretion (r = -0.308; p < 0.05).
Conclusions
These data suggest that lower potassium intakes are associated with greater wave reflection and stiffer arteries in young healthy adults.
doi:10.1186/1475-2891-13-39
PMCID: PMC4036422  PMID: 24775098
Potassium; Sodium; Wave reflection; Arterial stiffness
4.  Salt and blood pressure in Belgium. 
Blood pressure, pulse rate, body weight, and height were measured on two occasions in the inhabitants of a random 10% sample of households in a Belgian village. Twenty-four-hour urinary excretion of creatinine, sodium, and potassium was also determined. In subjects over the age of 19 there was a significant correlation for both systolic and diastolic pressure with age and body weight and, in women, also with pulse rate. After adjusting for these three variables, the systolic blood pressure in men was negatively correlated with the daily urinary potassium excretion, and the diastolic blood pressure in women negatively with the urinary sodium: creatinine ratio. The present data, obtained within one society, do not support a role for dietary sodium in the distribution of blood pressure within this population. Comparison of the present results with data from other countries does not refute the salt-genetic hypothesis but suggests also that a high potassium intake may lower blood pressure.
PMCID: PMC1052173  PMID: 7338700
5.  Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach 
PLoS Medicine  2008;5(3):e52.
Background
Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.
Methods and Findings
We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66–3.55, p = 4.8 × 10−6) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17–2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39–9.49, p = 1.1 × 10−12) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18–6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.
Conclusions
These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Using a mendelian randomization approach Sarah Lewis and colleagues find strong support for the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Editors' Summary
Background.
High blood pressure (hypertension) is a common medical condition that affects nearly a third of US and UK adults. Hypertension has no symptoms but can lead to heart attacks or strokes. It is diagnosed by measuring blood pressure—the force that blood moving around the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic pressure) and lowest when it is filling up with blood (diastolic pressure). Normal blood pressure is defined as a systolic pressure of less than 130 millimeters of mercury (mmHg) and a diastolic pressure of less than 85 mmHg (a blood pressure of 130/85). A reading of more than 140/90 indicates hypertension. Many factors affect blood pressure, but overweight people and individuals who eat too much salty or fatty foods are at high risk of developing hypertension. Mild hypertension can often be corrected by lifestyle changes, but many people also take antihypertensive drugs to reduce their blood pressure.
Why Was This Study Done?
Another modifiable lifestyle factor thought to affect blood pressure is alcohol intake. Observational studies that ask people about their drinking habits and measure their blood pressure suggest that alcohol intake correlates with blood pressure, but they cannot prove a causal link because of “confounding”—other risk factors associated with alcohol drinking, such as diet, might also affect the study participant's blood pressures. A trial that randomly assigns people to different alcohol intakes could provide this proof of causality, but such a trial is impractical. In this study, therefore, the researchers have used “Mendelian randomization” to investigate whether alcohol intake affects blood pressure. An inactive variant of aldehyde dehydrogenase 2 (ALDH2; the enzyme that removes alcohol from the body) has been identified. People who inherit the variant form of this gene from both parents have an ALDH2 *2*2 genotype (genetic makeup) and become flushed and nauseated after drinking. Consequently, they drink less than people with a *1*2 genotype and much less than those with a *1*1 genotype. Because inheritance of these genetic variants does not affect lifestyle factors other than alcohol intake, an association between ALDH2 genotypes and blood pressure would indicate that alcohol intake has an effect on blood pressure without any confounding.
What Did the Researchers Do and Find?
The researchers identified ten published studies (mainly done in Japan where the ALDH2 gene variant is common) on associations between ALDH2 genotype and blood pressure or hypertension using a detailed search protocol (a “systematic review”). A meta-analysis (a statistical method for combining the results of independent studies) of the studies that had investigated the association between ALDH2 genotype and hypertension showed that men with the *1*1 genotype (highest alcohol intake) and those with the *1*2 genotype (intermediate alcohol intake) were 2.42 and 1.72 times more likely, respectively, to have hypertension than those with the *2*2 genotype (lowest alcohol intake). There was no association between ALDH2 genotype and hypertension among the women in these studies because they drank very little. Systolic and diastolic blood pressures showed a similar relationship to ALDH2 genotype in a second meta-analysis of relevant studies. Finally, the researchers estimated that for men the lifetime effect of drinking 1 g of alcohol a day (one unit of alcohol contains 8 g of alcohol in the UK and 14 g in the US; recommended daily limits in these countries are 3–4 and 1–2 units, respectively) would be an increase in systolic blood pressure of 0.24 mmHg.
What Do These Findings Mean?
These findings support the suggestion that alcohol has a marked effect on blood pressure and hypertension. Consequently, some cases of hypertension could be prevented by encouraging people to reduce their daily alcohol intake. Although the Mendelian randomization approach avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks. Alternatively, ALDH2 could affect blood pressure independent of alcohol intake. The possibility that ALDH2 could effect blood pressure independently of alcohol is intake made unlikely by the fact that no effect of genotype on blood pressure is seen among women who drink very little. Additional large-scale studies are needed to address these possibilities, to confirm the current finding in more people, and to improve the estimates of the effect that alcohol intake has on blood pressure.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050052.
The MedlinePlus encyclopedia has a page on hypertension (in English and Spanish)
The American Heart Association provides information for patients and health professionals about hypertension
The UK Blood Pressure Association provides information for patients and health professionals on all aspects of hypertension, including information about alcohol affects blood pressure
The Explore@Bristol science center (a UK charity) provides an alcohol unit calculator and information on the effects of alcohol
The International Center for Alcohol Policies provides drinking guidelines for countries around the world
doi:10.1371/journal.pmed.0050052
PMCID: PMC2265305  PMID: 18318597
6.  Lifestyle modifications to prevent and control hypertension. 1. Methods and an overview of the Canadian recommendations. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada 
OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on lifestyle changes to prevent and control hypertension in otherwise healthy adults (except pregnant women). OPTIONS: For people at risk for hypertension, there are a number of lifestyle options that may avert the condition--maintaining a healthy body weight, moderating consumption of alcohol, exercising, reducing sodium intake, altering intake of calcium, magnesium and potassium, and reducing stress. Following these options will maintain or reduce the risk of hypertension. For people who already have hypertension, the options for controlling the condition are lifestyle modification, antihypertensive medications or a combination of these options; with no treatment, these people remain at risk for the complications of hypertension. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period January 1996 to September 1996 for each of the interventions studied. Reference lists were scanned, experts were polled, and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: Lifestyle modification by means of weight loss (or maintenance of healthy body weight), regular exercise and low alcohol consumption will reduce the blood pressure of appropriately selected normotensive and hypertensive people. Sodium restriction and stress management will reduce the blood pressure of appropriately selected hypertensive patients. The side effects of these therapies are few, and the indirect benefits are well known. There are certainly costs associated with lifestyle modification, but they were not measured in the studies reviewed. Supplementing the diet with potassium, calcium and magnesium has not been associated with a clinically important reduction in blood pressure in people consuming a healthy diet. RECOMMENDATIONS: (1) It is recommended that health care professionals determine the body mass index (weight in kilograms/[height in metres]2) and alcohol consumption of all adult patients and assess sodium consumption and stress levels in all hypertensive patients. (2) To reduce blood pressure in the population at large, it is recommended that Canadians attain and maintain a healthy body mass index. For those who choose to drink alcohol intake should be limited to 2 or fewer standard drinks per day (maximum of 14/week for men and 9/week for women). Adults should exercise regularly. (3) To reduce blood pressure in hypertensive patients, individualized therapy is recommended. This therapy should emphasize weight loss for overweight patients, abstinence from or moderation in alcohol intake, regular exercise, restriction of sodium intake and, in appropriate circumstances, individualized cognitive behaviour modification to reduce the negative effects of stress. VALIDATION: The recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth international Conference on Preventive Cardiology. They are similar to those of the World Hypertension League and the Joint National committee, with the exception of the recommendations on stress management, which are based on new information. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at health Canada, and the Heart and Stroke Foundation of Canada.
PMCID: PMC1230333  PMID: 10333847
7.  Sodium and potassium intake and blood pressure change in childhood. 
BMJ : British Medical Journal  1990;300(6729):899-902.
OBJECTIVE--To assess the association between sodium and potassium intake and the rise in blood pressure in childhood. DESIGN--Longitudinal study of a cohort of children with annual measurements during an average follow up period of seven years. SETTING--Epidemiological survey of the population of a suburban town in western Netherlands. SUBJECTS--Cohort of 233 children aged 5-17 drawn at random from participants in the population survey. MAIN OUTCOME MEASURES--At least six annual timed overnight urine samples were obtained. The mean 24 hour sodium and potassium excretion during the follow up period was estimated for each participant and the sodium to potassium ratio calculated. Individual slopes of blood pressure over time were calculated by linear regression analysis. RESULTS--No significant association was observed between sodium excretion and the change in blood pressure over time. The mean systolic blood pressure slopes, however, were lower when potassium intake was higher (coefficient of linear regression -0.045 mm Hg/year/mmol; 95% confidence interval -0.069 to -0.020), and the change in systolic pressure was greater when the urinary sodium to potassium ratio was higher (0.356 mm Hg/year/unit; 95% confidence interval 0.069 to 0.642). In relation to potassium this was interpreted as a rise in blood pressure that was on average 1.0 mm Hg (95% confidence interval -1.65 to -0.35) lower in children in the upper part of the distribution of intake compared with those in the lower part. The mean yearly rise in systolic blood pressure for the group as a whole was 1.95 mm Hg. Urinary electrolyte excretion was not associated with diastolic blood pressure. CONCLUSION--Dietary potassium and the dietary sodium to potassium ratio are related to the rise in blood pressure in childhood and may be important in the early pathogenesis of primary hypertension.
PMCID: PMC1662662  PMID: 2337712
8.  Urinary angiotensinogen as a potential biomarker of severity of chronic kidney diseases 
We previously reported that urinary excretion rates of angiotensinogen (AGT) provide a specific index of the activity of the intrarenal renin-angiotensin system in angiotensin II-dependent hypertensive rats. Meanwhile, we have recently developed direct enzyme-linked immunosorbent assays (ELISAs) to measure plasma and urinary AGT in humans. This study was performed to test a hypothesis that urinary AGT levels are enhanced in chronic kidney disease (CKD) patients and correlated with some clinical parameters. Eighty patients with CKD (37 women and 43 men, from 18 to 94 years old) and seven healthy volunteers (two women and five men, from 27 to 43 years old) were included. Plasma AGT levels showed a normal distribution; however, urinary AGT-creatinine ratios (UAGT/UCre) deviated from the normal distribution. When a logarithmic transformation was executed, Log(UAGT/UCre) levels showed a normal distribution. Therefore, Log(UAGT/UCre) levels were used for further analyses. Log(UAGT/UCre) levels were not correlated with age, gender, height, body weight, body mass index, systolic blood pressure, diastolic blood pressure, serum sodium levels, serum potassium levels, urinary sodium-creatinine ratios, plasma renin activity, or plasma AGT levels. However, Log(UAGT/UCre) levels were significantly correlated positively with urinary albumin-creatinine ratios, fractional excretion of sodium, urinary protein-creatinine ratios, and serum creatinine, and correlated negatively with estimated glomerular filtration rate. Log(UAGT/UCre) levels were significantly increased in CKD patients compared with control subjects (1.8801 ± 0.0885 vs. 0.9417 ± 0.1048; P = .0024). These data confirmed our earlier report and showed that a new ELISA assay is a valid approach for measuring urinary AGT.
doi:10.1016/j.jash.2008.04.008
PMCID: PMC2574500  PMID: 18958182
Blood pressure; ELISA; renin-angiotensin system; plasma
9.  Cross-Sectional Study of 24-Hour Urinary Electrolyte Excretion and Associated Health Outcomes in a Convenience Sample of Australian Primary Schoolchildren: The Salt and Other Nutrients in Children (SONIC) Study Protocol 
JMIR Research Protocols  2015;4(1):e7.
Background
Dietary sodium and potassium are involved in the pathogenesis of cardiovascular disease. Data exploring the cardiovascular outcomes associated with these electrolytes within Australian children is sparse. Furthermore, an objective measure of sodium and potassium intake within this group is lacking.
Objective
The primary aim of the Salt and Other Nutrient Intakes in Children (“SONIC”) study was to measure sodium and potassium intakes in a sample of primary schoolchildren located in Victoria, Australia, using 24-hour urine collections. Secondary aims were to identify the dietary sources of sodium and potassium, examine the association between these electrolytes and cardiovascular risk factors, and assess children’s taste preferences and saltiness perception of manufactured foods.
Methods
A cross-sectional study was conducted in a convenience sample of schoolchildren attending primary schools in Victoria, Australia. Participants completed one 24-hour urine collection, which was analyzed for sodium, potassium, and creatinine. Completeness of collections was assessed using collection time, total volume, and urinary creatinine. One 24-hour dietary recall was completed to assess dietary intake. Other data collected included blood pressure, body weight, height, waist and hip circumference. Children were also presented with high and low sodium variants of food products and asked to discriminate salt level and choose their preferred variant. Parents provided demographic information and information on use of discretionary salt. Descriptive statistics will be used to describe sodium and potassium intakes. Linear and logistic regression models with clustered robust standard errors will be used to assess the association between electrolyte intake and health outcomes (blood pressure and body mass index/BMI z-score and waist circumference) and to assess differences in taste preference and discrimination between high and low sodium foods, and correlations between preference, sodium intake, and covariates.
Results
A total of 780 children across 43 schools participated. The results from this study are expected at the end of 2015.
Conclusions
This study will provide the first objective measure of sodium and potassium intake in Australian schoolchildren and improve our understanding of the relationship of these electrolytes to cardiovascular risk factors. Furthermore, this study will provide insight into child taste preferences and explore related factors. Given the cardiovascular implications of consuming too much sodium and too little potassium, monitoring of these nutrients during childhood is an important public health initiative.
doi:10.2196/resprot.3994
PMCID: PMC4319086  PMID: 25592666
sodium, dietary; sodium chloride, dietary; potassium, dietary; child; urine specimen collection; blood pressure; obesity; taste; Australia
10.  Urinary and dietary sodium and potassium associated with blood pressure control in treated hypertensive kidney transplant recipients: an observational study 
BMC Nephrology  2012;13:121.
Background
In kidney transplant (Kt) recipients , hypertension is a major risk for cardiovascular complications but also for graft failure. Blood pressure (BP) control is therefore mandatory. Office BP (OBP) remains frequently used for clinical decisions, however home BP (HBP) have brought a significant improvement in the BP control. Sodium is a modifiable risk factor, many studies accounted for a decrease of BP with a sodium restricted diet. Increased potassium intake has been also recommended in hypertension management. Using an agreement between office and home BP, the present study investigated the relations between the BP control in Kt recipients and their urinary excretion and dietary consumption of sodium and potassium.
Methods
The BP control defined by OBP <140/90 mmHg and HBP <135/85 mmHg was tested in 70 Kt recipients (mean age 56 ± 11.5 years; mean graft survival 7 ± 6.6 years) treated with antihypertensive medications. OBP and HBP were measured with a validated oscillometric device (Omron M6®). The 24-hour urinary sodium (Na+) and potassium (K+) excretions as well as dietary intakes were compared between controlled and uncontrolled (in office and at home) recipients. Non parametric Wilcoxon Mann–Whitney Test was used for between groups comparisons and Fisher's exact test for frequencies comparisons. Pearson correlation coefficients and paired t-test were used when sample size was >30.
Results
Using an agreement between OBP and HBP, we identified controlled (21%) and uncontrolled recipients (49%). Major confounding effects susceptible to interfere with the BP regulation did not differ between groups, the amounts of sodium excretion were similar (154 ± 93 vs 162 ± 88 mmol/24 h) but uncontrolled patients excreted less potassium (68 ± 14 vs 54 ± 20 mmol/24 h; P = 0.029) and had significantly lower potassium intakes (3279 ± 753 vs 2208 ± 720 mg/24 h; P = 0.009), associated with a higher urinary Na+/K + ratio. Systolic HBP was inversely and significantly correlated to urinary potassium (r = −0.48; P = 0.002), a positive but non significant relation was observed with urinary sodium (r = 0,30;P = 0.074).
Conclusions
Half of the treated hypertensive Kt recipients remained uncontrolled in office and at home. Restoring a well-balanced sodium/potassium ratio intakes could be a non pharmacological opportunity to improve blood pressure control.
doi:10.1186/1471-2369-13-121
PMCID: PMC3506486  PMID: 23013269
Kidney transplantation; Office blood pressure; Home blood pressure; Sodium; Potassium; Urinary sodium/potassium ratio
11.  Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations. Intersalt Cooperative Research Group. 
BMJ : British Medical Journal  1996;312(7041):1249-1253.
OBJECTIVES--To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age. DESIGN--Standardised cross sectional study within and across populations. SETTING--52 population samples in 32 countries. SUBJECTS--10,074 men and women aged 20-59. MAIN OUTCOME MEASURES--Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias. Relation of sample median daily urinary sodium excretion to difference in blood pressure with age. RESULTS--In within population analyses (n = 10,074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses). Associations were larger at ages 40-59. In cross population analyses (n = 52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg. CONCLUSIONS--The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies. Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood. These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels.
PMCID: PMC2351086  PMID: 8634612
12.  Influence of increased adrenergic activity and magnesium depletion on cardiac rhythm in alcohol withdrawal. 
British Heart Journal  1994;72(6):554-560.
OBJECTIVE--To investigate the prevalence of arrhythmias in alcoholic men during detoxification and its relation to neuroendocrine activation and electrolyte disturbances. DESIGN--Consecutive case-control study. SETTING--Primary and secondary care, detoxification ward. PATIENTS AND CONTROLS--19 otherwise healthy alcoholic men (DSM-III-R) with withdrawal symptoms necessitating detoxification in hospital. 19 age matched, healthy non-alcoholic men as controls for Holter recordings. INTERVENTIONS--Treatment with chlomethiazole; additional treatment with carbamazepine in patients with previous seizures. MAIN OUTCOME MEASURES--Computer based analyses of mean heart rate and arrhythmias from 24 hour Holter recordings, 24 hour urinary excretion of adrenaline and noradrenaline, magnesium retention measured by means of intravenous loading test, and serum concentrations of electrolytes. RESULTS--The 24 hour mean heart rate was higher in the alcoholic men (97.4 beats/minute, 95% confidence interval (CI) 91.2 to 103.6) than in the controls (69.6 beats/minute, 95% CI 65.4 to 73.8, P < 0.001). However, there was no difference in diurnal heart rate variation. The prevalence of premature supraventricular depolarisations was lower in the alcoholic men (P < 0.05). Neither atrial fibrillation nor malignant ventricular arrhythmias occurred. The sinus tachycardia in the alcoholic men correlated with the concomitant urinary excretion of catecholamines (P < 0.05). The mean serum magnesium concentration was 0.78 mmol/l (95% CI 0.73 to 0.83) in the alcoholic men and 0.83 mmol/l (95% CI 0.81 to 0.85) in a reference population of 55 men aged 40. Magnesium depletion (defined as magnesium retention > 30%) was detected in 10 alcoholic men (53%). Three alcoholic men had serum potassium concentrations < or = 3.3 mmol/l on admission. CONCLUSION--Increased adrenergic activity, magnesium depletion, and hypokalaemia are often seen after heavy drinking, but in alcoholic men without clinical heart disease these changes were not accompanied by arrhythmias other than sinus tachycardia during detoxification in hospital.
PMCID: PMC1025642  PMID: 7857739
13.  Urinary cadmium and lead concentrations and their relation to blood pressure in a population with low exposure. 
The 24 hour urinary excretion of cadmium (U-Cd) and lead (U-Pb), and the excretion of beta-2- microglobulins and retinol binding protein concentration in spot urines, were determined in a random 4% sample of the population of a small Belgian town. Blood pressure and body weight were measured on two separate occasions. U-Cd averaged 2.4 nmol/24 h in 46 youths, increased with age, and was significantly higher in 57 adult men as compared with 59 women (9.3 v 7.2 nmol/24 h; p less than 0.01). U-Pb averaged 28 nmol/24 h in youths and similarly increased with age: adult men excreted more lead than women (64 v 40.0 nmol/24 h; p less than 0.001). Among men, manual workers excreted more cadmium (12.6 v 7.5 nmol/24 h; p less than 0.05) but a similar amount of lead (62 v 61 nmol/24 h) compared with office workers. After adjusting for sex and age, U-Cd and U-Pb were not related to body weight and cigarette consumption. In simple regression analysis, U-Cd was positively correlated with both systolic (r = +0.30; p less than 0.05) and diastolic (r = +0.38; p less than 0.01) blood pressure in women. After adjusting for other contributing variables, however, a weak but negative relation became apparent between systolic pressure and U-Cd in women (t = -2.21; p = 0.033) and between diastolic pressure and U-Cd in men (t = -2.04; p = 0.047). In women urinary beta-2-microglobulin was related to diastolic pressure (r-0.44; p<0.01) and after adjusting for age to both systolic (t=2.75; p=0.009) and diastolic (t=-3.07; p=0.004) pressure. In none of the sex-age groups did U-Pb and retinol binding protein contribute to the blood pressure variability.
PMCID: PMC1009290  PMID: 6372852
14.  High Sodium Intake in Women with Metabolic Syndrome 
Korean Circulation Journal  2014;44(1):30-36.
Background and Objectives
Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome.
Subjects and Methods
Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis.
Results
Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001).
Conclusion
Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.
doi:10.4070/kcj.2014.44.1.30
PMCID: PMC3905113  PMID: 24497887
Sodium, dietary; Metabolic syndrome; Hypertension
15.  Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation. 
BMJ : British Medical Journal  1989;298(6668):227-230.
OBJECTIVE--To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN--Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING--Patients attending diabetic outpatient clinic of city hospital. PATIENTS--Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS--After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT--Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS--Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS--Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.
Images
PMCID: PMC1835532  PMID: 2493869
16.  Urinary kallikrein and plasma renin activity as determinants of renal blood flow. The influence of race and dietary sodium intake. 
Journal of Clinical Investigation  1977;60(1):129-138.
We investigated the relationship of the kallikrein-kinin system and the renin-angiotensin system in the regulation of blood pressure, salt and water excretion, and renal blood flow. Normotensive and hypertensive black and white men were studied during unresticted sodium intake as well as on a 10-meq/day sodium intake; potassium intake was held constant throughout the study (80 meq/day). During unrestricted sodium intake, urinary kallikrein activity was greater in white normotensives than white hypertensives or black normotensives. There was no difference (P greater than 0.05) between white and black hypertensives or between black normotensives and black hypertensives. All groups had greater urinary kallikrein activity on low sodium vs. unrestricted sodium intake, but the increase in black hypertensives was small, and they excreted significantly less kallikrein than the ogher groups on the low sodium diet. Plasma renin activity showed similar increments after sodium restriction in all groups. Urinary kallikrein activity correlated with renal blood flow in all groups except the black normotensives on low sodium intake. Renal blood flow could be correlated uniformly with log (urinary kallikrein activity/supine plasma renin activity) in all groups on either diet. Urinary sodium and potassium excretion and urine volume were not different among the groups. We conclude: (a) important racial differences exist in urinary kallikrein activity that are unrelated to sodium or potassium excretion or urine volume; (b) dietary sodium restriction further delineates racial differences and suggests alternative pathophysiologic mechanisms for huma hypertension; (c) urinary kallikrein activity correlates with renal blood flow; and (d) our data support the concept that the kallikrein-kinin system and the renin-angiotensin system contribute to the regulation of renal blood flow and may account for racial differences in renal vascular resistance.
PMCID: PMC372351  PMID: 874078
17.  Dietary and Urinary Metabonomic Factors Possibly Accounting for Higher Blood Pressure of African-Americans Compared to White Americans – – The INTERMAP Study RR 
Hypertension  2013;62(6):1074-1080.
African-Americans compared to non-Hispanic-White-Americans have higher systolic, diastolic blood pressure and rates of prehypertension/hypertension. Reasons for these adverse findings remain obscure. Analyses here focused on relations of foods/nutrients/urinary metabolites to higher African-American blood pressure for 369 African-Americans compared to 1,190 non-Hispanic-White-Americans ages 40-59 from 8 population samples. Standardized data were from four 24-hour dietary recalls/person, two 24-h urine collections, 8 blood pressure measurements; multiple linear regression quantitating role of foods, nutrients, metabolites in higher African-American blood pressure. Compared to non-Hispanic-White-Americans, African-Americans average systolic/diastolic pressure was higher by 4.7/3.4 mm Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of African-American women reduced excess African-American systolic/diastolic pressure to 6.8/3.8 mm Hg. African American intake of multiple foods, nutrients related to blood pressure was less favorable - - less vegetables, fruits, grains, vegetable protein, glutamic acid, starch, fiber, minerals, potassium; more processed meats, pork, eggs, sugar-sweetened beverages, cholesterol, higher sodium to potassium ratio. Control for 11 nutrient and 10 non-nutrient correlates reduced higher African-American systolic/diastolic pressure to 2.3/2.3 mm Hg (52% and 33% reduction) (men) and to 5.3/2.8 mm Hg (21% and 27% reduction) (women). Control also for foods/urinary metabolites had little further influence on higher African-American blood pressure. Multiple nutrients with less favorable intakes by African-Americans than non-Hispanic-White-Americans account at least in part for higher African-American blood pressure. Improved dietary patterns can contribute to prevention/control of more adverse African-American blood pressure levels.
doi:10.1161/HYPERTENSIONAHA.113.01810
PMCID: PMC3912568  PMID: 24101663
African-American; blood pressure; nutrient; food intake; urinary metabolites
18.  Idiopathic Recurrent Calcium Urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ? A tripartite study in male patients providing insight into oxidative metabolism as possible driving force towards alteration of urine composition, calcium salt crystallization and stone formation* 
Background
In IRCU it is uncertain whether variation of urinary protein, especially non-albumin protein (NAlb-P), is due to the presence of stones or reflects alteration of oxidative metabolism.
Aims
To validate in a tripartite cross-sectional study of 187 ambulatory male patients, undergoing a standardized laboratory programme, whether stones impact on N-Alb-P or the state of oxidative metabolism interferes with IRCU pathophysiology.
Methods
In part 1 the strata low and high of fasting urinary excretion rate per 2 h of N-Alb-P, malonedialdehyde, hypoxanthine, xanthine, pH and other urine components were compared, and association with renal stones in situ evaluated; in part 2 the co-variation of oxidatively modulated environment, fasting urinary pH, calcium (Ca) salt crystallization risk and the number of patients with stones in situ was examined; in part 3, the nucleation of Ca oxalate and Ca phosphate was tested in undiluted postprandial urine of patients and related to the state of oxidative metabolism.
Results
In part 1, N-Alb-P excretion > 4.3 mg was associated with increase of blood pressure, excretion of total protein, hypoxanthine (a marker of tissue hypoxia), malonedialdehyde (a marker of lipid peroxidation), sodium, magnesium, citrate, uric acid, volume, pH, and increase of renal fractional excretion of both NAlb-P and uric acid; when stones were present, urinary pH was elevated but other parameters were unaffected. Significant predictors of N-Alb-P excretion were malonedialdehyde, fractional N-Alb-P and hypoxanthine. In part 2, urine pH > 6.14 was associated with unchanged blood pressure and plasma vasopressin, increase of blood pH, urinary volume, malonedialde hyde, fractional excretion of N-Alb-P, uric acid, Ca phosphate, but not Ca oxalate, supersaturation; this spectrum was accompanied by decrease of concentration of urinary total and free magnesium, total and complexed citrate, plasma uric acid (in humans the major circulating antioxidant) and insulin; the number of stone-bearing patients was increased. Significant predictors of urine pH were body mass index, plasma insulin and uric acid (negative), and urinary xanthine (positive). In part 3 low plasma uric acid, not high urinary malonedialdehyde or high ratio malonedialdehyde/uric acid was significantly associated with diminished Ca but not oxalate tolerance, with the first nucleating crystal type being mostly Ca phosphate (hydroxyapatite), in the rest Ca oxalate dihydrate; uricemia correlated marginally positively (p = 0.055) with Ca tolerance of urine, stronger with blood pressure and insulin, and negatively with urinary xanthine, fractional N-Alb-P, volume, sodium.
Conclusions
In IRCU 1) not renal stones in situ, but disturbed oxidative metabolism apparently modulates nephron functionality, ending up in higher renal NAlb-P release, urinary volume, sodium and pH of fasting urine; 2) etiologically unknown decline of uricemia may represent antioxidant deficiency and cause a risk of hydroxyapatite crystallization and stone formation in a weakly acidic or alkaline inhibitor-deficient and NAlb-P-rich milieu; 3) several observations, linking oxidative and systemic metabolism, are compatible with Ca stone initiation beyond tubules.
doi:10.1186/2047-783X-14-9-378
PMCID: PMC3351970  PMID: 19748857
Calcium urolithiasis; Stones in situ; Urinary protein; Oxidative and systemic metabolism; Urinary pH; Calcium salt crystallization
19.  Evidence for Environmental Familiality of Kallikrein Excretion in Utah Kindreds 
Western Journal of Medicine  1986;144(5):559-563.
In investigating the role of urinary kallikrein in the pathophysiology of hypertension, we measured 12-hour kallikrein excretion in 1,100 persons in 68 Utah kindreds. The kallikrein excretion was statistically adjusted to account for variations in body size and urine output.
Adjusted kallikrein excretion was greater in youths than in adults and correlated with potassium excretion and sodium excretion in persons with normal blood pressure. It was decreased in normotensive subjects with strong family histories of stroke and hypertension, but was not significantly different in adults with hypertension.
Adjusted kallikrein excretion was correlated between pairs of siblings, parent-offspring pairs and spouses. Our results indicate that kallikrein excretion is a familial variable, with the familiality due more to shared environmental than genetic factors.
PMCID: PMC1306703  PMID: 3636040
20.  Estimation of salt intake by 24-hour urinary sodium excretion: a cross-sectional study in Yantai, China 
BMC Public Health  2014;14:136.
Background
High levels of dietary sodium are associated with raised blood pressure and adverse cardiovascular health. To determine baseline salt intake, we investigated the average dietary salt intake from 24-hour urinary sodium excretion with a small sample of Yantai adults in the Shandong province of China.
Methods
One hundred ninety one adults aged 18–69 years were randomly selected from the Yantai adult population. Blood pressure, anthropometric indices and sodium excretion in a 24-hour urine collection were measured. Consumption of condiments was derived from 3-day weighted records. Completeness of urine collections was verified using creatinine excretion in relation to weight.
Results
The mean Na and K outputs over 24 hours were 201.5 ± 77.7 mmol/day and 46.8 ± 23.2 mmol/day, respectively (corresponding to 11.8 g NaCl and 1.8 g K). Overall, 92.1% of the subjects (96.9% of men and 87.1% of women) had intakes of over 6 g salt (NaCl)/d. The main sources of salt intake from weighed condiments records were from home cooking salt (74.7%) followed by soy sauce (15.0%). Salt intake from condiments and salt excretion were weakly correlated((r = 0.20, p = 0.005).A positive linear correlation between salt intake was associated with systolic blood pressure in all adjusted and unadjusted model (r = 0.16, p = 0.01). Each 100 mmol/day increase in sodium intake was associated with a 4.0 mmHg increase in systolic blood pressure.
Conclusion
Dietary salt intake in Yantai adults was high. Reducing the intake of table salt and soy sauce used in cooking will be an important strategy to reduce sodium intake among Yantai adults.
doi:10.1186/1471-2458-14-136
PMCID: PMC3921994  PMID: 24507470
Urinary sodium; Salt intake; Urine
21.  Association of Filtered Sodium Load With Medullary Volumes and Medullary Hypoxia in Hypertensive African Americans as Compared With Whites 
Background
African-Americans (AA) develop hypertension earlier with more target manifestations than Whites despite having higher GFR for any level of serum creatinine.
Study Design and Participants
This study tested the hypothesis that increased GFR and sodium reabsorption in AA is associated with increased metabolic work and medullary hypoxia in 49 non-diabetic, essential hypertensive subjects (29 Whites and 20 AAs) taking constant sodium diet (150 mEq/d) and renin-angiotensin system blockade.
Predictors
Ethnicity, age, measured GFR, sodium excretion, and body mass index.
Outcomes
We examined cortical and medullary volumes and blood flows using multi-detector CT and intra-renal deoxyhemoglobin (R2*) using blood oxygen level dependent (BOLD) MR.
Results
Blood pressure and sodium excretion were similar, while AA were more obese and had higher iothalamate GFR. Renal cortical volumes did not differ, but medullary volumes adjusted for body size and age were higher in AA (32.3 ± 11.2 vs 24.9±7.4 cc/m2 BSA, p<.001). Sodium reabsorption and blood flows were higher in AA. Basal cortical deoxyhemoglobin was similar between ethnic groups, while medullary R2* was higher in AA (39.7± 5.1 vs 36.3± 6.5 /sec, p=.02), but fell to levels similar to Whites after furosemide. The circulating isoprostane prostaglandin F2α was higher in AA and daily urinary prostaglandin F2α excretion in AAs correlated directly with renal blood flow (R=0.71, p<.01).
Limitations
Studies were limited to treated, volunteer subjects with normal kidney function without knowledge of prior nutrient intake.
Conclusions
These data demonstrate for the first time that increased sodium reabsorption in obese, hypertensive AA patients was associated with enlarged medullary volumes, functional hypoxia related to solute reabsorption, and a direct relationship between blood flows and urinary isoprostanes. Our results support a model of increased oxygen consumption and oxidative stress in AA that may accelerate hypertension and target-organ injury compared to white essential hypertensive patients.
doi:10.1053/j.ajkd.2011.09.023
PMCID: PMC3259240  PMID: 22130642
Hypertension; ethnicity; GFR; oxidative stress; BOLD MR; hemodynamics
22.  Severe electrolyte disorders following cardiac surgery: a prospective controlled observational study 
Critical Care  2004;8(6):R459-R466.
Introduction
Electrolyte disorders are an important cause of ventricular and supraventricular arrhythmias as well as various other complications in the intensive care unit. Patients undergoing cardiac surgery are at risk for development of tachyarrhythmias, especially in the period during and immediately after surgical intervention. Preventing electrolyte disorders is thus an important goal of therapy in such patients. However, although levels of potassium are usually measured regularly in these patients, other electrolytes such as magnesium, phosphate and calcium are measured far less frequently. We hypothesized that patients undergoing cardiac surgical procedures might be at risk for electrolyte depletion, and we therefore conducted the present study to assess electrolyte levels in such patients.
Methods
Levels of magnesium, phosphate, potassium, calcium and sodium were measured in 500 consecutive patients undergoing various cardiac surgical procedures who required extracorporeal circulation (group 1). A total of 250 patients admitted to the intensive care unit following other major surgical procedures served as control individuals (group 2). Urine electrolyte excretion was measured in a subgroup of 50 patients in both groups.
Results
All cardiac patients received 1 l cardioplegia solution containing 16 mmol potassium and 16 mmol magnesium. In addition, intravenous potassium supplementation was greater in cardiac surgery patients (mean ± standard error: 10.2 ± 4.8 mmol/hour in cardiac surgery patients versus 1.3 ± 1.0 in control individuals; P < 0.01), and most (76% versus 2%; P < 0.01) received one or more doses of magnesium (on average 2.1 g) for clinical reasons, mostly intraoperative arrhythmia. Despite these differences in supplementation, electrolyte levels decreased significantly in cardiac surgery patients, most of whom (88% of cardiac surgery patients versus 20% of control individuals; P < 0.001) met criteria for clinical deficiency in one or more electrolytes. Electrolyte levels were as follows (mmol/l [mean ± standard error]; cardiac patients versus control individuals): phosphate 0.43 ± 0.22 versus 0.92 ± 0.32 (P < 0.001); magnesium 0.62 ± 0.24 versus 0.95 ± 0.27 (P < 0.001); calcium 1.96 ± 0.41 versus 2.12 ± 0.33 (P < 0.001); and potassium 3.6 ± 0.70 versus 3.9 ± 0.63 (P < 0.01). Magnesium levels in patients who had not received supplementation were 0.47 ± 0.16 mmol/l in group 1 and 0.95 ± 0.26 mmol/l in group 2 (P < 0.001). Urinary excretion of potassium, magnesium and phosphate was high in group 1 (data not shown), but this alone could not completely account for the observed electrolyte depletion.
Conclusion
Patients undergoing cardiac surgery with extracorporeal circulation are at high risk for electrolyte depletion, despite supplementation of some electrolytes, such as potassium. The probable mechanism is a combination of increased urinary excretion and intracellular shift induced by a combination of extracorporeal circulation and decreased body temperature during surgery (hypothermia induced diuresis). Our findings may partly explain the high risk of tachyarrhythmia in patients who have undergone cardiac surgery. Prophylactic supplementation of potassium, magnesium and phosphate should be seriously considered in all patients undergoing cardiac surgical procedures, both during surgery and in the immediate postoperative period. Levels of these electrolytes should be monitored frequently in such patients.
doi:10.1186/cc2973
PMCID: PMC1065069  PMID: 15566592
cardiac surgery; electrolyte disorders; extracorporal circulation; hypokalaemia; hypomagnesaemia; hypophosphataemia; hypothermia; magnesium; potassium; phosphate
23.  The effect of salt usage behavior on sodium intake and excretion among Korean women 
Nutrition Research and Practice  2012;6(3):232-237.
This study was done to explore the effect of Korean women's salt usage behavior on their sodium intake and excretion according to aging. Dietary sodium intake and salt usage behavior were analyzed to compare the difference between young and middle-aged women. One hundred fifty six young women and 77 middle-aged women without hypertension or any current medication were recruited. Body mass index, waist hip ratio, blood pressure were measured from each subject. Salt usage behaviors were surveyed with questionnaire, sodium intake with 24-hr recall method, and sodium excretion with spot urine. Middle-aged women were more obese than young women according to body mass index and waist hip ratio. Blood pressure was significantly higher for the middle-aged. Young women consumed more fats and middle-aged women more carbohydrates. Middle-aged women consumed more sodium and potassium, and excreted more sodium. Among questionnaire items, kimchi, soup or pot stew, or salted vegetables were found to be related with high sodium diet. Salted vegetables and salted nuts and potato chips were significantly correlated with young women's high sodium diet, while soy sauce on fried food, kimchi, salted vegetables accounted for middle-aged women's high sodium diet. With these results, we concluded that middle-aged women consumed more carbohydrates, less fat, and more sodium and potassium than young women. Middle-aged women frequently choose kimchi, soup or pot stew, or salted vegetables, and they contribute to high sodium intake. We recommend to choose low-salt kimchi, less soup or pot stew, and more fresh vegetables for lower sodium diet.
doi:10.4162/nrp.2012.6.3.232
PMCID: PMC3395789  PMID: 22808348
Sodium intake; salt usage behavior; low sodium diet; blood pressure
24.  Are Sodium Transporters in Urinary Exosomes Reliable Markers of Tubular Sodium Reabsorption in Hypertensive Patients? 
Nephron. Physiology  2010;114(3):p25-p34.
Background
Altered renal sodium handling has a major pathogenic role in salt-sensitive hypertension. Renal sodium transporters are present in urinary exosomes. We hypothesized that sodium transporters would be excreted into the urine in different amounts in response to sodium intake in salt-sensitive versus salt-resistant patients.
Methods
Urinary exosomes were isolated by ultracentrifugation, and their content of Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC) was analyzed by immunoblotting. Animal studies: NKCC2 and NCC excretion was measured in 2 rat models to test whether changes in sodium transporter excretion are indicative of regulated changes in the kidney tissue. Human studies: in hypertensive patients (n = 41), we investigated: (1) a possible correlation between sodium reabsorption and urinary exosomal excretion of sodium transporters, and (2) the profile of sodium transporter excretion related to blood pressure (BP) changes with salt intake. A 24-hour ambulatory BP monitoring and a 24-hour urine collection were performed after 1 week on a low- and 1 week on a high-salt diet.
Results
Animal studies: urinary NKCC2 and NCC excretion rates correlated well with their abundance in the kidney. Human studies:6 patients (15%) were classified as salt sensitive. The NKCC2 and NCC abundance did not decrease after the high-salt period, when the urinary sodium reabsorption decreased from 99.7 to 99.0%. In addition, the changes in BP with salt intake were not associated with a specific profile of exosomal excretion.
Conclusions
Our results do not support the idea that excretion levels of NKCC2 and NCC via urinary exosomes are markers of tubular sodium reabsorption in hypertensive patients.
doi:10.1159/000274468
PMCID: PMC2840242  PMID: 20068364
Exosomes; Na-Cl cotransporter; Na-K-2Cl cotransporter; Renal sodium transporters; Salt sensibility; Urine biomarkers
25.  Relation of Urinary Calcium and Magnesium Excretion to Blood Pressure 
American Journal of Epidemiology  2011;174(1):44-51.
Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40–59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20–59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels.
doi:10.1093/aje/kwr049
PMCID: PMC3159430  PMID: 21624957
blood pressure; calcium; magnesium

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