Etiology-based dietary approach for managing hyperkalemia in people with chronic kidney disease.

Diet therapy for hyperkalemia in chronic kidney disease (CKD) is at a crossroads: many researchers and clinicians are no longer recommending the low-potassium diet, which has defined practice for the last half century, and instead are favoring a high-potassium, plant-rich diet. Central to this shift is the observation that reported dietary potassium intake is not associated with plasma potassium concentrations. However, kinetic studies using potassium salts indicate that people with CKD have impaired potassium tolerance that may make them susceptible to transient increases in plasma potassium levels from dietary potassium (postprandial hyperkalemia). Observational studies generally measure plasma potassium in the fasting state and before hemodialysis treatment, and therefore may not detect the acute effects of dietary potassium on plasma potassium concentrations. Differences between the acute and chronic effects of dietary potassium on plasma potassium levels may help explain clinical experiences and case studies attributing hyperkalemic episodes in patients with CKD to intakes of high-potassium foods despite their apparent lack of association. To reconcile these findings, an etiology-based approach to managing hyperkalemia is proposed in this review. The approach combines key elements of the low-potassium and plant-rich diets, and adds new features of meal planning to lower the risk of postprandial hyperkalemia.

The Dietary Approach to the Treatment of the Rare Genetic Tubulopathies Gitelman's and Bartter's Syndromes.

Gitelman's (GS) and Bartter's (BS) syndromes are rare, inherited autosomal recessive tubulopathies characterized by hypokalemia, metabolic alkalosis, renal sodium, chloride, and potassium and magnesium-wasting. While the treatment based on potassium, sodium, chloride, and magnesium supplementation in addition to other pharmacologic options are widely established, recommendations about the dietary approach to GS and BS still remain generic. In this review we focus on the dietary strategies to increase sodium, potassium, and magnesium intake in GS and BS patients. Potassium and magnesium-rich foods and supplements are considered together with those that may reduce through different mechanisms the potassium and magnesium plasma level. Magnesium supplementation is often poorly tolerated, causing abdominal pain and diarrhea in most patients. New formulations using liposome and, in particular, sucrosomial technology have been recently proposed for magnesium supplementation in order to increase magnesium supplement tolerability and intestinal absorption. The dietary approach to GS and BS may be very important in the therapeutic approach to these syndromes. Due to the relevance of the dietary approach to these syndromes, a nutritional counseling should always be recommended and the nutritionist should join nephrologists in the follow-up of GS and BS patient care.

Association of Dietary Potassium Intake with the Development of Chronic Kidney Disease and Renal Function in Patients with Mildly Decreased Kidney Function: The Korean Multi-Rural Communities Cohort Study.

BACKGROUND Dietary potassium has negative outcomes in patients with mildly impaired kidney function, while having positive outcomes in patients with hypertension. The association of dietary potassium intake with chronic kidney disease (CKD) development, with presence of hypertension, was studied in the Korean rural population with mildly impaired kidney function. MATERIAL AND METHODS From 3 rural areas of Korea, 5064 participants age ≥40 with CKD stage 2 at baseline were recruited. Patients were classified according to the quartile of dietary potassium intake. Newly developed CKD, defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² at the time of follow-up, and eGFR decline, defined as eGFR decrease >15% at follow-up, were studied. The effect of dietary potassium on CKD development and eGFR decline were studied by Cox proportional hazard models. The association of potassium with blood pressures and C-reactive protein was also studied to examine the underlying mechanisms. RESULTS Compared to 8.6% in normotensives, 15.7% of hypertensives developed CKD. The hazard ratio (HR) (95% confidence interval) of CKD was lower in high potassium diet only in hypertensives, with 0.60 (0.37-0.99) in the highest quartile. The eGFR decline was also lower in patients with higher potassium diet, with 0.70 (0.50-0.98) in Q3 and 0.54 (0.34-0.85) in Q4. Potassium intake has also been shown to decrease high diastolic blood pressure development (>90 mmHg) in hypertensives at 0.45 (0.25-0.83). CONCLUSIONS Dietary potassium was associated with lower risk of CKD development and eGFR decline, and this association was observed only in hypertensives.

Hypocalcaemia and hyponatraemia masquerading the diagnosis of Gitelman syndrome.

Gitelman syndrome is the most common renal tubulopathy, recently exhibiting a dramatic rise of incidence in Asia.A 50-year-old woman presented with vomiting, fatigue and quadriparesis. Physical examination revealed a positive Trousseau sign , hypotonia and areflexia.Suspecting hypocalcaemia, she was given intravenous 10% calcium gluconate (10 mL administered slowly over 10 min) but her manifestations persisted. An exhaustive laboratory work up revealed the diagnosis of Gitelman syndrome.The peculiarity of this case however, is entailed in its coexistence with hypocalcaemia and hyponatraemia. In addition, the age of primary presentation being 50 years further culminates its atypicality.Multiple electrolyte imbalances were corrected by oral and intravenous supplementation and a high sodium-potassium diet was advocated. Administration of spironolactone imposed a pitfall in the management of our patient due to exacerbation of pre-existing hyponatraemia.On follow-up, her electrolyte profile was stable and corresponding symptoms were alleviated.

Hypokalaemia periodic paralysis.

Hypokalaemic periodic paralysis is a rare skeletal muscle channelopathy causing flaccid paralysis, which predominantly presents in adolescents and young adults. I report a case of a 33-year-old Caucasian man who presented with sudden onset paralysis, following previous similar presentations without investigation. Blood tests revealed undetectable serum potassium levels in the context of paralysis. Other causes of hypokalaemia were excluded, and the patient was treated with planned lifelong prophylactic potassium replacement for a diagnosis of primary hypokalaemic periodic paralysis. This case demonstrates that, although rare, hypokalaemic periodic paralysis should be considered as a differential diagnosis in young patients who present with sudden flaccid paralysis and can easily be excluded by checking serum potassium levels at presentation.

Higher adherence to the Mediterranean diet is inversely associated with having hypertension: is low salt intake a mediating factor?

Blood pressure (BP) is a major risk factor for population health worldwide and a preventable disease through lifestyle modification. The aim of this study was to assess the association between adherence to the Mediterranean diet (MD) and occurrence of hypertension in a Mediterranean cohort. Demographic and dietary data of 1937 adults were collected in 2014-2015 from the general population of Catania, Sicily (Italy). Food frequency questionnaires and a MD adherence score were used to assess exposure variables. Higher adherence to the MD was inversely associated with hypertension. However, this association was no more significant after adjustment for sodium and potassium intake. These results suggest that salt may exert a mediating effect of high adherence to the MD towards hypertension.

Postprandial effect to decrease soluble epoxide hydrolase activity: roles of insulin and gut microbiota.

Epoxides of free fatty acids (FFAs), especially epoxyeicosatrienoic acids (EETs), are lipid mediators with beneficial effects in metabolic and cardiovascular (CV) health. FFA epoxides are quickly metabolized to biologically less active diols by soluble epoxide hydrolase (sEH). Inhibition of sEH, which increases EET levels, improves glucose homeostasis and CV health and is proposed as an effective strategy for the treatment of diabetes and CV diseases. Here, we show evidence that sEH activity is profoundly reduced in postprandial states in rats; plasma levels of 17 sEH products (i.e., FFA diols), detected by targeted oxylipin analysis, all decreased after a meal. In addition, the ratios of sEH product to substrate (sEH P/S ratios), which may reflect sEH activity, decreased ~70% on average 2.5 h after a meal in rats (P<.01). To examine whether this effect was mediated by insulin action, a hyperinsulinemic-euglycemic clamp was performed for 2.5 h, and sEH P/S ratios were assessed before and after the clamp. The clamp resulted in small increases rather than decreases in sEH P/S ratios (P<.05), indicating that insulin cannot account for the postprandial decrease in sEH P/S ratios. Interestingly, in rats treated with antibiotics to deplete gut bacteria, the postprandial effect to decrease sEH P/S ratios was completely abolished, suggesting that a gut bacteria-derived factor(s) may be responsible for the effect. Further studies are warranted to identify such a factor(s) and elucidate the mechanism by which sEH activity (or sEH P/S ratio) is reduced in postprandial states.

Relationship between sodium and potassium intake and blood pressure in a sample of overweight adults.

OBJECTIVE: The aim of this study was to examine the relationship between sodium and potassium intakes and blood pressure (BP) in a clinical sample. METHODS: Secondary analysis of baseline data from 328 participants (mean age: 43.6 ± 8 y, mean body mass index [BMI]: 32.4 ± 4.2 kg/m2, mean systolic BP [SBP]/diastolic BP [DBP]: 124.9 ± 14.5/73.3 ± 9.9 mm Hg) of the 12-mo HealthTrack randomized controlled weight loss trial was conducted. Resting BP and 24-h urine sodium and potassium were measured. Dietary intake was evaluated with 4-d food records and self-reported diet histories. RESULTS: Urinary sodium was positively correlated (Spearman's rho) with SBP (r = 0.176; P = 0.001) and DBP (r = 0.150; P = 0.003). The ratio of sodium to potassium was positively correlated with SBP (r = 0.1; P = 0.035). Urinary sodium (F [4,323] = 20.381; P < 0.0005; adjusted R2 = 0.231) and sodium-to-potassium ratio (F[4,323] = 25.008; P < 0.0005; adjusted R2 = 0.227) significantly predicted SBP after controlling for age, sex, BMI, and hypertension medication use. Dietary sodium and potassium significantly predicted urinary sodium (B = 0.33, t = 4.032, P < 0.01) and potassium (B = 0.67, t = 8.537, P < 0.01) excretion, respectively, after adjustment for energy and BMI. Median dietary sodium intake was 3197 mg/d and median dietary potassium intake was 2886 mg/d. Cereal-based products and dishes were the major contributors (22%) to total sodium intake. CONCLUSIONS: In the present study, a high dietary sodium intake and high sodium-to-potassium ratio predicted high SBP. This suggests a need to focus dietary advice on reduction of sources of sodium and increasing sources of potassium in weight loss interventions to improve BP control.

Dietary Intake and Sources of Potassium and the Relationship to Dietary Sodium in a Sample of Australian Pre-School Children.

The aim of this study was to determine the intake and food sources of potassium and the molar sodium:potassium (Na:K) ratio in a sample of Australian pre-school children. Mothers provided dietary recalls of their 3.5 years old children (previous participants of Melbourne Infant Feeding Activity and Nutrition Trial). The average daily potassium intake, the contribution of food groups to daily potassium intake, the Na:K ratio, and daily serves of fruit, dairy, and vegetables, were assessed via three unscheduled 24 h dietary recalls. The sample included 251 Australian children (125 male), mean age 3.5 (0.19) (SD) years. Mean potassium intake was 1618 (267) mg/day, the Na:K ratio was 1.47 (0.5) and 54% of children did not meet the Australian recommended adequate intake (AI) of 2000 mg/day for potassium. Main food sources of potassium were milk (27%), fruit (19%), and vegetable (14%) products/dishes. Food groups with the highest Na:K ratio were processed meats (7.8), white bread/rolls (6.0), and savoury sauces and condiments (5.4). Children had a mean intake of 1.4 (0.75) serves of fruit, 1.4 (0.72) dairy, and 0.52 (0.32) serves of vegetables per day. The majority of children had potassium intakes below the recommended AI. The Na:K ratio exceeded the recommended level of 1 and the average intake of vegetables was 2 serves/day below the recommended 2.5 serves/day and only 20% of recommended intake. An increase in vegetable consumption in pre-school children is recommended to increase dietary potassium and has the potential to decrease the Na:K ratio which is likely to have long-term health benefits.

The Effect of the Sodium to Potassium Ratio on Hypertension Prevalence: A Propensity Score Matching Approach.

This study investigated the effect of the sodium to potassium ratio on hypertension prevalence and blood pressure. The study population was constructed by pooling the Korean National Health and Nutrition Examination Surveys between 2010 and 2014. The study population was divided into quartiles based on the sodium to potassium ratio, and the effect was inferred by the difference in hypertension prevalence across quartiles by six pairwise comparisons using a propensity score matching technique. The quartiles with the higher sodium to potassium ratio had higher hypertension prevalence rates based on the following pairwise comparisons: the first vs. third quartile, the first vs. fourth quartile, the second vs. third quartile, and the second vs. fourth quartile. The prevalence differences were 2.74% point (p < 0.05), 3.44% point (p < 0.01), 2.47% point (p < 0.05), and 2.95% point (p < 0.01), respectively. In addition, statistically significant higher systolic (p < 0.05) and diastolic blood pressure (p < 0.01) was observed in the second quartiles compared to the first quartiles. Because a strong association was also detected between the sodium to potassium ratio and blood pressure even at a low level of sodium to potassium ratio, a lower sodium to potassium ratio diet than a usual diet is recommended to control high blood pressure in Korea.

Potassium Intake, Bioavailability, Hypertension, and Glucose Control.

Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+) ATPase pump. Approximately 90% of potassium consumed (60-100 mEq) is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect health outcomes. Hypertension (HTN) is the leading cause of cardiovascular disease (CVD) and a major financial burden ($50.6 billion) to the US public health system, and has a significant impact on all-cause morbidity and mortality worldwide. The relationship between increased potassium supplementation and a decrease in HTN is relatively well understood, but the effect of increased potassium intake from dietary sources on blood pressure overall is less clear. In addition, treatment options for hypertensive individuals (e.g., thiazide diuretics) may further compound chronic disease risk via impairments in potassium utilization and glucose control. Understanding potassium bioavailability from various sources may help to reveal how specific compounds and tissues influence potassium movement, and further the understanding of its role in health.

Effects of potassium supplementation on markers of osmoregulation and volume regulation: results of a fully controlled dietary intervention study.

OBJECTIVE: Lifestyle measures including dietary sodium restriction and increased potassium intake are recognized to lower blood pressure (BP). Potassium was found to be effective in reducing BP at higher levels of sodium intake, but to have little effect when sodium intake is restricted. The humoral mechanisms underlying these sodium intake dependent effects of potassium are unknown. We investigated the effects of potassium supplementation on top of a fully controlled sodium-restricted diet on markers of osmoregulation and volume regulation. METHODS: In this post-hoc analysis, we included 35 (pre)hypertensive individuals participating in a randomized, double-blind, placebo-controlled crossover trial. Individuals received capsules containing sodium [3.0 g (130 mmol)/day], potassium [2.8 g (72  mmol)/day], or placebo for three four-week periods. Linear mixed-effect models were used to estimate the effects of potassium supplementation compared with placebo. Skewed data were ln-transformed before analysis. RESULTS: Increased potassium intake was associated with a significant decrease in 24-h BP (-3.6/-1.6 mmHg). Furthermore, we found a significant decrease in ln MR-proANP [-0.08 (95% confidence interval -0.15, -0.01) pmol/l, P = 0.03] and significant increases in 24-h heart rate [2.5 (0.9, 4.0) bpm, P = 0.002], ln plasma copeptin [0.11 (0.01, 0.20) pmol/l, P = 0.02], ln renin [0.34 (0.08, 0.60) µIU/ml, P = 0.01], and ln aldosterone [0.14 (0.07, 0.22) nmol/l, P < 0.001] compared with placebo. CONCLUSIONS: We found that potassium has BP-lowering effects during sodium restriction. These BP-lowering effects, however, seem mitigated by several counter regulatory mechanisms (i.e. increased secretion of vasopressin, stimulation of RAAS, and increased heart rate) that were activated to maintain volume homeostasis and counterbalance the decrease in BP.

Dietary acid load in early life and bone health in childhood: the Generation R Study.

BACKGROUND: Dietary contribution to acid-base balance in early life may influence subsequent bone mineralization. Previous studies reported inconsistent results regarding the associations between dietary acid load and bone mass. OBJECTIVE: We examined the associations of dietary acid load in early life with bone health in childhood. DESIGN: In a prospective, multiethnic, population-based cohort study of 2850 children, we estimated dietary acid load as dietary potential renal acid load (dPRAL), based on dietary intakes of calcium, magnesium, phosphorus, potassium, and protein, and as a protein intake to potassium intake ratio (Pro:K) at 1 y of age and in a subgroup at 2 y of age : Bone mineral density, bone mineral content (BMC), area-adjusted BMC, and bone area were assessed by dual-energy X-ray absorptiometry at the median age of 6 y. Data were analyzed by using multivariable linear regression models. RESULTS: After adjusting for relevant maternal and child factors, dietary acid load estimated as either dPRAL or Pro:K ratio was not consistently associated with childhood bone health. Associations did not differ by sex, ethnicity, weight status, or vitamin D supplementation. Only in those children with high protein intake in our population (i.e., >42 g/d), a 1-unit increase in dPRAL (mEq/d) was inversely associated with BMC (difference: -0.32 g; 95% CI: -0.64, -0.01 g). CONCLUSIONS: Dietary acid load in early life was not consistently associated with bone health in childhood. Further research is needed to explore the extent to which dietary acid load in later childhood may affect current and future bone health.

Identification of a dietary pattern prospectively associated with bone mass in Australian young adults.

BACKGROUND: Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual. OBJECTIVES: We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults. DESIGN: The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age. RESULTS: We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area. CONCLUSIONS: A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age. Our results indicate that high consumption of low-fat dairy products, whole grains, and vegetables in adolescence are associated with beneficial effects on bone development.

Dietary magnesium and potassium intakes and circulating magnesium are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the EPIC-Norfolk cohort study.

BACKGROUND: In our aging population, maintenance of bone health is critical to reduce the risk of osteoporosis and potentially debilitating consequences of fractures in older individuals. Among modifiable lifestyle and dietary factors, dietary magnesium and potassium intakes are postulated to influence bone quality and osteoporosis, principally via calcium-dependent alteration of bone structure and turnover. OBJECTIVE: We investigated the influence of dietary magnesium and potassium intakes, as well as circulating magnesium, on bone density status and fracture risk in an adult population in the United Kingdom. DESIGN: A random subset of 4000 individuals from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of 25,639 men and women with baseline data was used for bone density cross-sectional analyses and combined with fracture cases (n = 1502) for fracture case-cohort longitudinal analyses (mean follow-up 13.4 y). Relevant biological, lifestyle, and dietary covariates were used in multivariate regression analyses to determine associations between dietary magnesium and potassium intakes and calcaneal broadband ultrasound attenuation (BUA), as well as in Prentice-weighted Cox regression to determine associated risk of fracture. Separate analyses, excluding dietary covariates, investigated associations of BUA and fractures with serum magnesium concentration. RESULTS: Statistically significant positive trends in calcaneal BUA for women (n = 1360) but not men (n = 968) were apparent across increasing quintiles of magnesium plus potassium (Mg+K) z score intake (P = 0.03) or potassium intake alone (P = 0.04). Reduced hip fracture risk in both men (n = 1958) and women (n = 2755) was evident for individuals in specific Mg+K z score intake quintiles compared with the lowest. Statistically significant trends in fracture risk in men across serum magnesium concentration groups were apparent for spine fractures (P = 0.02) and total hip, spine, and wrist fractures (P = 0.02). None of these individual statistically significant associations remained after adjustment for multiple testing. CONCLUSIONS: These findings enhance the limited literature studying the association of magnesium and potassium with bone density and demonstrate that further investigation is warranted into the mechanisms involved and the potential protective role against osteoporosis.

Clinical perspectives on the rationale for potassium supplementation.

Hypokalemia is a common electrolyte disturbance, observed in > 20% of hospitalized patients. Hypokalemia, although not formally defined, is generally considered to be when serum potassium levels fall below the normal value of 3.6 mmol/L. In contrast to other electrolytes, potassium is primarily an intracellular ion: only 2% of all potassium in the body is present in the extracellular fluid, so a small decrease in serum potassium may represent a significant decrease in intracellular potassium. Individuals with mildly decreased potassium levels (3.0-3.5 mmol/L) may be asymptomatic, but patients with more pronounced decreases may report symptoms including muscle weakness, fatigue, and constipation. Very low serum potassium levels (≤ 2.5 mmol/L) can lead to muscle necrosis, paralysis, cardiac arrhythmias, and impaired respiration, which can be life-threatening. Absent comprehensive and robust treatment guidelines, strategies for the prevention or treatment of hypokalemia, such as how to diagnose hypokalemia, when to treat patients, what dosage regimen of potassium supplementation to use and for how long, are often based on the experience of the physician and empirical evidence. However, proper evaluation and treatment of hypokalemia in patients is essential because of associated morbidities. Because small potassium deficits in serum represent large body losses, potassium repletion requires substantial and prolonged supplementation. For patients with known risk factors for hypokalemia (e.g. hypertension, heart failure, or diabetes), careful monitoring is crucial to avoid the adverse sequelae associated with potassium deficits and to ensure that adequate and timely preventive measures can be taken. In this review, we provide practical insights into the etiology, differential diagnosis, and treatment of hypokalemia, including treatment strategies for patients with known risk factors.

Effect of dried California Mission figs on mineral status and food replacement.

OBJECTIVE: Figs are a rich source of several different minerals and fibres. We studied the effect of the consumption of dried California Mission figs on mineral and nutrient levels, as well as the effect of the addition of figs to a self-selected habitual diet on dietary patterns. DESIGN: A crossover randomized controlled trial study design in which participants with a mean of age of approximately 56 years were randomly assigned to eat either their usual diet for 5 weeks or to add dried California Mission figs (120 g/d) to their usual diet for 5 weeks, after which they crossed over to the other group for an additional 5 weeks. Six 24 h dietary recalls and four blood samples were obtained from each participant. SETTING: Loma Linda University School of Public Health, USA. SUBJECTS: A follow-up study using data collected from eighty-eight American males and females from September to December 2008. RESULTS: Diets reported in the 24 h dietary recall during the fig-supplemented diet period were significantly higher in Ca and K in the dietary and total phase (P value<0·05). Nevertheless, data on mineral levels in the body gathered by means of biochemical analyses from blood samples were nearly the same for both the figs-added and the participants' standard diet. The estimated displacement suggests that eating figs resulted in the elimination of 4% of desserts, 5% of vegetables, 10% of dairy products, 23% of grain products and 168% of beverages from other sources that participants would otherwise consume. CONCLUSIONS: Based on 24 h dietary recalls, the daily consumption of figs may increase the intake of several different minerals. However, mineral levels in blood samples were not altered significantly.