Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on hypoglycemia and potassium reduction.

STUDY OBJECTIVE: Recent studies have identified that reduced alternative intravenous insulin doses, such as 5 units or 0.1 units/kg, may reduce the risk of hypoglycemia compared to standard doses of 10 units in patients treated for hyperkalemia. However, some studies suggest that these alternative doses may reduce the ability to lower serum potassium. This study was performed to determine the impact of alternative insulin dosing on hypoglycemia and potassium reduction in patients with hyperkalemia. DESIGN: Meta-analysis. DATA SOURCE: PubMed/MEDLINE, CENTRAL, Ovid, and ClinicalTrials.gov were searched from inception through November 2020. PATIENTS: Patients treated with standard (10 units) or alternative (<10 units) insulin dosing strategies for hyperkalemia. Only studies that evaluated hypoglycemia (serum glucose <70 mg/dl), severe hypoglycemia (serum glucose <50 mg/dl), and potassium reduction post-treatment were included in the meta-analysis. All articles were assessed for bias using the Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa scales for randomized prospective trials and retrospective trials, respectively. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Ten retrospective cohort studies (n = 3437) were included and had low- or moderate-risk of bias. Alternative insulin dosing strategies included 5 units, 0.1 units/kg, and <10 units. Alternative dosing had lower pooled odds of hypoglycemia (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.43-0.69, I2  = 8%) and severe hypoglycemia (OR 0.41, 95% CI 0.27-0.64, I2  = 0%). No difference in potassium reduction was detected (mean difference -0.02 mmol/L, 95% CI -0.11-0.07, I2  = 53%). CONCLUSIONS: Alternative insulin dosing strategies for hyperkalemia management resulted in less hypoglycemia and severe hypoglycemia without compromising potassium reduction compared to standard dose. Prospective studies are needed to confirm these findings.

Rise in Potassium Deficiency in the US Population Linked to Agriculture Practices and Dietary Potassium Deficits.

This paper, for the first time, provides evidence that current practices that lead to agricultural crop removal of potassium are unsustainable and likely contributed to the decline in dietary potassium intake and rise in hypokalemia prevalence in the US population. Potassium concentrations in beef, pork, turkey, fruit, vegetables, cereal crops, and so forth decreased between 1999 and 2015 based on the examination of potassium values of food items of USDA standard reference. Ratios of potassium input to removal by crops between 1987 and 2014, potassium in topsoil, and crop-available soil potassium in US farms all declined in recent years. Reported reductions in dietary potassium intake correspond to these decreases in the food supply and to increases in hypokalemia prevalence in the US population. Results of this paper provide new understanding on links between potassium management in agricultural practices and potassium intake deficits, which is needed for combating increasing hypokalemia prevalence in the US population.

Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.

Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.

Association between hypokalemia and small bowel capsule endoscopy completion rates in patients in South China: A prospective single-center study.

BACKGROUND/AIMS: Approximately 20-30% of small bowel capsule endoscopies (SBCEs) do not reach the cecum at the completion of the examination. We aimed to determine whether hypokalemia influences the completion rate and small bowel transit time (SBTT) of SBCE. PATIENTS AND METHODS: From January to December 2017, 112 patients (18-75 years old) who underwent SBCE were assessed consecutively for enrolment in our study. On the day of the procedure, a blood test was performed prior to capsule ingestion. The completion rate, gastric transit time (GTT), SBTT, and diagnostic yield were recorded for each SBCE. RESULTS: The SBCE completion rate was lower in the hypokalemia group than that in the normal potassium group (55.6% (15/27) vs. 76.5% (65/85), P = 0.036). The median GTT was 55.5 ± 47.1 min in the hypokalemia group and 46.7 ± 44.5 min in the normal potassium group (P > 0.05). The median SBTT was 412.8 ± 123.3 min in the hypokalemia group and 367.3 ± 172.5 min in the normal potassium group (P > 0.05). The diagnostic yields of the hypokalemia and normal potassium groups were 74.1% and 78.8%, respectively (P = 1.00). CONCLUSION: Hypokalemia may decrease the SBCE completion rate. Physicians should consider the possibility of hypokalemia after bowel preparation because this condition is not rare. Potassium deficiencies should be rectified prior to performing SBCE procedures to increase the SBCE completion rate.

Contemporary Dietary Intake: Too Much Sodium, Not Enough Potassium, yet Sufficient Iodine: The SALMEX Cohort Results.

Initiatives to reduce sodium intake are encouraged globally, yet there is concern about compromised iodine intake supplied through salt. The aim of the present study was to determine baseline sodium, potassium, and iodine intake in a sample of workers from our Institution in Mexico City (SALMEX Cohort). Methods. From a cohort of 1009 workers, appropriate 24-h urine and three-day dietary recall was collected in a sample of 727 adult subjects for assessment of urinary sodium, potassium, and iodine concentrations. Median urinary iodine excretion (UIE) was compared across categories of sodium intake of <2, 2⁻3.6, and ≥3.6 g/day. Results. Average sodium intake was 3.49 ± 1.38 g/day; higher in men than women (4.14 vs. 3.11 g/day, p ≤0.001). Only 10.6% of the population had sodium intake within the recommended range (<2 g/day); 45.4% had high (2⁻3.6 g/day) and 44% had excessive intake (>3.6 g/day). Average urinary Na/K ratio was 3.15 ± 1.22 (ideal < 1), higher in men (3.42 vs. 3.0, p ≤ 0.001). The multivariate analysis showed that sodium intake was associated with age (p = 0.03), male sex (p < 0.001), caloric intake (p = 0.002), UKE (p < 0.001) and BMI (p < 0.001). Median iodine intake was 286.7 µg/day (IQR 215⁻370 µg/day). Less than 2% of subjects had iodine intake lower than recommended for adults (95 µg/day); 1.3% of subjects in the recommended range of salt intake had low iodine intake. There is a direct relationship between iodine and sodium urinary excretion (r = 0.57, p < 0.0001). Conclusions. In the studied population, there was an excessive sodium intake and an imbalance between sodium and potassium intake. Only 10.6% of the population had sodium intake within the recommended values, but iodine intake in this group appears to be adequate.

Associations between dietary salt, potassium and blood pressure in South African adults: WHO SAGE Wave 2 Salt & Tobacco.

BACKGROUND & AIMS: In June 2016, South Africa implemented legislation mandating maximum sodium levels in a range of processed foods with a goal of reducing population salt intake and disease burden from hypertension. Our aim was to explore the relationship between salt and blood pressure (BP) in a subsample of the World Health Organization Study on global AGEing and adult health (SAGE) Wave 2 before implementation of legislation in South Africa. METHODS & RESULTS: Blood pressure (BP) was measured in triplicate (n = 2722; median age 56 years; 33% male) and 24-h urine collected in a nested subsample (n = 526) for sodium, potassium and creatinine analysis. Hypertension prevalence was 55% in older adults (50-plus years) and 28% in younger adults (18-49 years). Median salt intake (6.8 g/day) was higher in younger than older adults (8.6 g vs 6.1 g/day; p < 0.001), and in urban compared to rural populations (7.0 g vs 6.0 g/day; p = 0.033). Overall, 69% of participants had salt intakes above 5 g/day. Potassium intakes were generally low (median 35 mmol/day) with significantly lower intakes in rural areas and older adults. Overall, 91% of adults failed to meet the daily potassium recommendation of 90 mmol/d. Salt intakes above 5 g/day, and to a greater extent, a dietary sodium-to-potassium (Na:K) ratio above 2 mmol/mmol, were associated with significantly steeper regression slopes of BP with age. CONCLUSION: These preliminary results indicate that high dietary Na:K ratio may lead to a greater increase in BP and hypertension risk with age. Interventions to increase potassium intakes alongside sodium reduction initiatives may be warranted.

Excess dietary sodium and inadequate potassium intake in Italy: results of the MINISAL study.

OBJECTIVE: As excess sodium and inadequate potassium intake are causally related to hypertension and cardiovascular disease, the MINISAL-GIRCSI Program aimed to provide reliable estimates of dietary sodium and potassium intake in representative samples of the Italian population. DESIGN AND METHODS: Random samples of adult population were collected from 12 Italian regions, including 1168 men and 1112 women aged 35-79 yrs. Electrolyte intake was estimated from 24 hour urine collections and creatinine was measured to estimate the accuracy of the collection. Anthropometric indices were measured with standardised procedures. RESULTS: The average sodium excretion was 189 mmol (or 10.9 g of salt/day) among men and 147 mmol (or 8.5 g) among women (range 27-472 and 36-471 mmol, respectively). Ninety-seven % of men and 87% of women had a consumption higher than the WHO recommended target of 5g/day. The 24 h average potassium excretion was 63 and 55 mmol, respectively (range 17-171 and 20-126 mmol), 96% of men and 99% of women having an intake lower than 100 mmol/day (European and American guideline recommendation). The mean sodium/potassium ratio was 3.1 and 2.8 respectively, i.e. over threefold greater than the desirable level of 0.85. The highest sodium intake was observed in Southern regions. Sodium and potassium excretion were both progressively higher the higher the BMI (p < 0.0001). CONCLUSIONS: These MINISAL preliminary results indicate that in all the Italian regions thus far surveyed dietary sodium intake was largely higher and potassium intake lower than the recommended intakes. They also highlight the critical association between overweight and excess salt intake.

Dietary intake and nutritional deficiencies in patients with diabetic or idiopathic gastroparesis.

BACKGROUND & AIMS: Gastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis. METHODS: Patients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed. RESULTS: Caloric intake averaged 1168 ± 801 kcal/day, amounting to 58% ± 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B(6), C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08). CONCLUSIONS: Many patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies.

The role of dairy in meeting the recommendations for shortfall nutrients in the American diet.

BACKGROUND: The 2005 Dietary Guidelines Advisory Committee (DGAC) recognized calcium, potassium and magnesium, all found in high levels in dairy foods, among the shortfall nutrients in both children and adults' diets. OBJECTIVE: The objectives were to determine: 1) the percentage of the population with intakes greater than the Adequate Intakes (AI) for calcium and potassium and the percentage of the population with inadequate magnesium intake (based on Estimated Average Requirement [EAR]) and 2) the impact of various levels of dairy consumption on intake of calcium, potassium and magnesium. DESIGN: Secondary analysis of data from the 1999-2004 NHANES. SUBJECTS/ SETTING: Participants 2 years of age and older. MAIN OUTCOME MEASURES: Percentage of the population meeting current recommendations for calcium, potassium and magnesium. STATISTICAL ANALYSES PERFORMED: Percentage of EAR/AI for nutrients was calculated based on age/gender specific values. All analyses were weighted using the NHANES six-year sample weights and adjusted for the complex sample design of NHANES with the statistical package SUDAAN. RESULTS: The most recent NHANES data demonstrated that a significant proportion of the American population did not meet recommendations for calcium, potassium, and magnesium. Less than 3% of the population consumed the recommended level or more of potassium. Only 30% of the US population 2 years of age and older obtained the recommended level of calcium or more and 55% consumed less than the EAR for magnesium. Recommending 3-4 servings from the dairy group for all people greater than 9 years of age may be necessary in order to ensure adequate intake of calcium and magnesium, assuming the current diet remains the same. More than 4 servings of dairy would be needed to meet the potassium recommendation at all ages. CONCLUSIONS: For those individuals who do not consume dairy products, we need to better understand the barriers to consuming specific dairy products. In addition, more research is needed to examine whether food-based recommendations are practical, feasible and cost effective to meet nutrient needs.

Calcium, magnesium, potassium and sodium intakes in Japanese children aged 3 to 5 years.

The present study aimed to evaluate in preschool children the intakes of Ca, Mg that possibly affect health and tooth formation and the intakes of K and Na that may affect lifestyle-related diseases. Information on dietary intake was collected from 90 preschool children (15 boys and 15 girls each in the 3-, 4- and 5-year old groups) on 3 separate days in the school fiscal year 1999 (April 1999 to March 2000) by the duplicate-diet technique. The Ca, Mg, K, and Na concentrations were determined by atomic absorption spectrometry using wet-ashed samples. The medians of mean daily intakes of Ca, Mg, K and Na in 3- to 5-year-old children were 432 mg, 110 mg, 1.18 g and 1.60 g, respectively, and no significant differences with regard to gender were observed. Seasonal varia-tion of intake was seen for each mineral. Calcium intake in most preschool children did not meet adequate intake (AI), probably due to low intakes of milk and dairy products in Japan. Magnesium intake was below the estimated average requirement (EAR) in 13.3% of the subjects, while the K intake met the AI. Sodium intake in a quarter of preschool children exceeded the tentative dietary goal. We concluded that in Japanese children aged 3-5 years; Ca intake is low, Na intake is high, and K intake is adequate, but some children could be at risk for Mg deficiency.

Incidence and consequences of total body potassium depletion in chronic hemodialysis patients.

OBJECTIVE: This study determined relationship between total body potassium (TBK) and morbidity and mortality of patients with end stage renal disease (ESRD). DESIGN, PATIENTS, SETTING: Long term observational study of 15 ESRD patients receiving chronic hemodialysis in an academically affiliated Veterans Affairs Medical Center Hospital. METHODOLOGY AND OUTCOME MEASURE: TBK by whole-body counting of 40K, dialysis potassium losses, and patient demographic characteristics were determined. Survival was evaluated retrospectively after seven years of follow-up. RESULTS: Six of 15 patients (40%) had TBK depletion. All patients who were TBK depleted, expired by study end. In contrast, only 4 of 9 patients with normal K+ stores had died during the same time period (P<0.02). Median survival time of subjects with normal TBK was 100 vs 55 months for the depleted group (chi2=4.6, P<0.05). Patients with normal TBK were younger (41.9 vs 62.5 years, P<0.02) and predominantly black (78%). The ESRD group with normal TBK received more hours of hemodialysis (HD) per week (11.2 hours vs 9.7, P<0.02) and had greater K+ removal than the depleted patients (70.5 mmol/treatment vs 43.8). Urea reduction ratio was not statistically different between groups. Serum albumin, interdialytic increases in BUN and weight, and body mass index were not different between normal and TBK depleted groups. CONCLUSIONS: TBK depletion occurs in a significant proportion of HD patients and is associated with increased mortality. It is prudent to customize HD and dietary prescriptions to maintain normal levels of TBK in ESRD patients.

The spectrum of endemic renal tubular acidosis in the northeast of Thailand.

We have previously reported a high prevalence of endemic renal tubular acidosis (EnRTA) in the northeast of Thailand, and our subsequent studies provided evidence that K deficiency exists in the same region. Since tubulointerstitial damage is associated with K deficiency, we postulate that this might be implicated in the pathogenesis of EnRTA and, if so, that a spectrum of tubulointerstitial abnormalities can be anticipated. In this study we evaluated renal acidification ability in 4 patients and in 11 of their relatives. We used a 3-day acid load (NH4Cl 0.1 g/kg/day) followed by 20 mg oral furosemide and monitored the maximal renal concentrating ability using water deprivation and intranasal 1-deamino-D-arginine vasopressin. The results showed that the subjects could be divided into three groups; normal relatives of the patients, those with suspected renal tubular acidosis, and patients with overt EnRTA who had chronic metabolic acidosis and a low rate of excretion of NH4+. The rate of excretion of K was very low (20 +/- 4 mmol/day) in patients with EnRTA and in their relatives with suspected EnRTA. The transtubular K concentration gradient was also very low in their relatives, especially in patients with suspected EnRTA (2.8 +/- 0.2). With a 3-day NH4Cl load, the rate of excretion of NH4+ was very low in patients with EnRTA (32 +/- 9 mmol/day), and the relatives with suspected EnRTA also had a decreased capacity to excrete NH+4 (50 +/- 14 mmol/day). In contrast, the normal relatives excreted 92 +/- 12 mmol of NH+4/day. The patients with EnRTA could lower their urine pH to less than 5.5 after the acid loading (6.2 +/- 0.3). After furosemide (20 mg), the NH4+ excretion in the patients with EnRTA was lower than in the normal relatives. Moreover, the minimum urine pH in patients with EnRTA did not fall (6.1 +/- 0.2), but there was a fall to 4.8 +/- 0.1 in the patients with suspected EnRTA after furosemide treatment. In conclusion, there was a spectrum of tubulointerstitial abnormalities ranging from suspected to overt distal RTA in a geographic area known to have a high prevalence of K deficiency. K deficiency might be the important pathogenetic factor of EnRTA in the northeast of Thailand.

Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis.

Sudden unexplained nocturnal death (SUND), a disorder of unknown cause that occurs in otherwise healthy young adults, mostly male, during their sleep, is prevalent in the north-east region of Thailand, where it has been known for generations as lai tai. It occurs in the same population and area where hypokalaemic periodic paralysis (HPP), endemic distal renal tubular acidosis (EdRTA), and renal stones are also endemic. SUND has occurred in families of patients with EdRTA, and HPP can present as sudden onset of muscle parlysis with potentially lethal cardiac arrhythmias and respiratory failure from severe hypokalaemia occurring in the middle of the night. Surveys in which serum and urinary potassium have been measured indicate a deficiency of the electrolyte in the population. Potassium deficiency is probably the prime factor responsible for SUND and HPP. Low urinary citrate concentrations and the high prevalence of acidification defects in the population indicate that potassium deficiency is also responsible for the prevalence of EdRTA and for renal stones.

Prevalence of magnesium and potassium deficiencies in the elderly.

Concentrations of magnesium and potassium in erythrocytes and plasma were determined in a population of 381 unselected elderly men and women, most of them in their eighties. The effects of biological factors (age, sex, weight) and a large set of pathological conditions, malignant or not, were examined. Analyses of variance showed a relation between age and concentrations of plasma potassium and between weight and concentrations of plasma magnesium. The chi-square test showed correlations between low concentrations of plasma magnesium and diabetes, abuse of alcohol and tobacco, and also between low values for erythrocyte magnesium and hypertension. Low values for plasma potassium were correlated with hypertension whereas high values were correlated with cardiovascular disease. Although some of the differences in the mean concentrations observed were statistically significant, these differences were always small. Most interesting was the distribution of the concentrations of the cations. This study shows that assays of both of these cations in erythrocytes were better than assays in plasma to evidence a deficiency. Indeed, about 20% of the studied population had low concentrations of both erythrocyte potassium and magnesium, whereas 2 and 10% had low values for plasma potassium and magnesium, respectively. This study underlines the large prevalence of magnesium and potassium deficiencies in the elderly, an observation we could not attribute to pathology or treatment. Routine electrolyte studies therefore appear to be justified in aged human subjects.