Decrease In Serum Potassium Levels Research Articles

Compatibility of hypokalaemia caused by low-dose prednisolone plus abiraterone acetate therapy for metastatic castration-resistant prostate cancer

BackgroundThis study aimed to investigate the relationship between low-dose prednisolone (PSL) and the incidence of hypokalaemia at abiraterone acetate (abiraterone) plus PSL combination therapy targeting Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).MethodsThis retrospective observational study included 153 Japanese patients treated with abiraterone and PSL for mCRPC at Kariya Toyota General Hospital and Gifu General Medical Center between September 2014 and October 2022. The incidence of grade ≥ 2 hypokalaemia as well as serum potassium level variations and the continuous combination therapy duration were compared between the low-dose (5 mg/day of PSL) and the standard-dose (10 mg/day of PSL) groups.ResultsThis study included 153 patient of which 95 were matched to establish the analysis population. The low-dose and the standard-dose groups consisted of 13 and 82 patients, respectively. No significant difference in the incidence of grade ≥ 2 hypokalaemia was observed between the two groups [15.4% (2/13 patients) in the low-dose group and 12.2% (10/82 patients) in the standard-dose group, P = 0.667]. The low-dose group exhibited a decrease in serum potassium levels from 4.63 on day − 7 − 0 to 4.16 mmol/L on day 84 ± 10 (n = 7, P = 0.066), and serum potassium levels from day − 7 − 0 to 84 ± 10 in the low-dose group appeared to be great in the standard-dose group (n = 37, P = 0.475). The Kaplan–Meier curves for continuity of abiraterone and PSL therapy were not significantly different between the low-dose group (n = 13) and standard-dose group (n = 82, P = 0.427).ConclusionCombination therapy with abiraterone and 5 mg/day of PSL in Japanese patients with mCRPC did not change the incidence of grade ≥ 2 hypokalaemia. However, although not significant, 5 mg/day of PSL demonstrated a decreasing trend in serum potassium levels with a larger degree of change than that of 10 mg/day of PSL. Therefore, the combination of abiraterone and 5 mg/day PSL can be administered to Japanese patients with mCRPC. The patients must be monitored for hypokalaemia through measurement of serum potassium levels and observation of subjective symptoms such as muscle weakness, convulsion etc. In addition, the doctor or the pharmacist must explain these symptoms to the patient and instruct them to consult their medical staff immediately in the event of development of such symptoms.

The Effect of Renastart Formula Supplementation in Serum Electrolytes in Children with Acute Kidney Injury

Abstract Background patients of renal disease suffer from electrolyte disturbances including hyperkalemia, hyperphosphatemia, hyponatremia, hypocalcemia and hypermagnesemia. Unfortunately, patients with kidney disease require close monitoring for serum electrolytes to maintain normal levels; with traditional nutritional interventions they may need receiving potassium and phosphorus binders Aim: This study will concentrate on the effect and tolerability of Renastart formula supplementation on correction and maintaining serum levels of electrolytes in AKI or AKI on top of CKD pediatric patients. Methods Double arm clinical convenient trial, conducted in Pediatric Nephrology Unit,Ain Shams University, Cairo, Egypt, where 24 participants who had AKI or AKI on top of CKD with hyperphosphatemia and / or hyperkalemia were recruited, the mean of age of participants was 4.1±3.15 years ranged from 0.5 to 10 years. Subjects were divided into two groups, 12 patients per group (group A received a calcium carbonate (phosphorus binder) (9 patients) with dosage 45-65 mg/kg/day orally alone or withsodium polystyrene sulfonate (potassium binder) (11 patients) with dosage 0.5-1mg/kg/day oral and group B received Renastart formula supplemented with breast milk, standard infant formula or diet), the dosage ratio was adjusted to be 1:3 (Renastart was 1/4 daily caloric intake) if serum potassium level ≥5.5 - <6 meq/L and / or serum phosphorus > 7mg/dl. But, if potassium level was ≥ 6 meq/L, the ratio was 1:1 (Renastart was ½ daily caloric intake). Readjusting dosage ratio was according to serum electrolyte levels response for treatment. Follow up of serum levels of potassium was every day until its serum level returned to normal then every month for three months and serum phosphorus was every month for three consecutive months. Results All the included subjects in both groups had high serum potassium (> 5.5 meq/L) and / or high serum phosphorus (>7 mg/dl) upon enrollment, mean serum potassium and serum phosphorus were (5.7±0.41 meq/L) (7.2±1.6 mg/dl) respectively. Regarding the decrease of serum potassium, Renastart formula supplementation in group B and potassium binders in group A resulted in equal decrease in serum potassium levels; Potassium after 3 months of management in group B was (4.22±0.28 mEq/L) (p value between 3rd month- baseline month in group B p < 0.01) and potassium binders in group A (4.48±0.27 mEq/L) (p value between 3rd month – baseline month in group A p < 0.01). Renastart formula in group B ((potassium after 1 month of management = 4.7±0.32 meq/L) (p value between 1st month – baseline month in group B p < 0.01)) had more rapid effect than potassium binders in group A during 1st month of the study ((potassium after 1 month of management =5.1±0.41 meq/L) (p value between 1st month – baseline month in group A p > 0.05). Regarding decrease in serum phosphorus, Renastart formula supplementation in group B resulted in more decrease in serum phosphorus levels though both showed significant drop in phosphorus level (( serum phosphorus after 3 months of management = 4.60±0.29 mg/dl (p value between 3rd month – baseline month in group B p = 0.002)) in comparison to that achieved by phosphorus binders in group A ((5.21±0.29mg/dl) (p value between 3rd month – baseline month in group A p = 0.01)), moreover Renastart supplementation in group B was more rapid than phosphorus binders in group A in decrease serum phosphorus (p value between 1st month and baseline in group B p = 0.002) (p value between 1st month and baseline in group A p = 0.17) Conclusion We can conclude that Renastart formula supplementation was more rapid than potassium binders in decreasing serum potassium levels in AKI pediatric patients, moreover more effective and rapid than phosphorus binders in decreasing serum phosphorus.

A multicentral prospective cohort trial of a pharmacist-led nutritional intervention on serum potassium levels in outpatients with chronic kidney disease: The MieYaku-Chronic Kidney Disease project.

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.

Assessment of Patiromer Monotherapy for Hyperkalemia in an Acute Care Setting

Hyperkalemia is a common electrolyte disorder in hospitalized patients; however, the clinical usefulness of administering patiromer for reduction of serum potassium levels in this setting is unknown. To evaluate the outcomes associated with patiromer as monotherapy in patients with acute hyperkalemia in an acute care setting. This cohort study used electronic health record data from adult patients treated with patiromer for acute hyperkalemia in emergency departments, inpatient units, and intensive care units at an urban, academic medical center in the Bronx, New York, between January 30, 2018, and December 30, 2019. Data analysis was conducted between June 2020 and February 2021. A single dose of oral patiromer (8.4 g, 16.8 g, or 25.2 g). The primary outcome was the mean absolute reduction in serum potassium level from baseline at 3 distinct time intervals after patiromer administration: 0 to 6 hours, greater than 6 to 12 hours, and greater than 12 to 24 hours. Key secondary outcomes were the incidence of hypokalemia and potassium reduction stratified by baseline potassium level and care setting. Among 881 encounters of patiromer treatment, the mean (SD) age of patients was 67.4 (14.4) years; 463 encounters (52.6%) were for male patients, and most (338 [38.4%]) were for patients who identified as non-Hispanic Black. The mean (SD) baseline serum potassium level was 5.60 (0.35) mEq/L (to convert to mmol/L, multiply by 1.0), and within the first 6 hours after patiromer administration, the mean (SD) potassium reduction was 0.50 (0.56) mEq/L (P < .001). Both absolute and relative potassium reduction from baseline varied across baseline hyperkalemia severity but not by care setting. The lowest dose of patiromer (8.4 g) was used in 721 encounters (81.8%), and in 725 encounters (82.3%), no further doses of a potassium binder were required. Hypokalemia was noted in 2 encounters (0.2%) at 24 hours after patiromer administration. In this cohort study of patients with acute, non-life-threatening hyperkalemia, a single dose of patiromer was associated with a significant decrease in serum potassium levels and a low incidence of hypokalemia. These findings suggest that patiromer monotherapy may be useful in an institutional setting for managing elevated potassium levels and minimizing the risk of hypokalemia associated with other potassium control measures.

Plasma cortisol level and its relation to in-hospital mortality in acute kidney injury patients

Background Critically ill patients are at risk of developing critical illness-related corticosteroid insufficiency (CIRCI). This may present as hypotension, unresponsiveness to catecholamine infusions, and/or ventilator dependence. Acute kidney injury (AKI) usually complicates critically ill patients and is associated with hemodynamic instability. There is usually failure to predict the severity and to assess the response to therapy in AKI. The aim of this study was to assess the plasma cortisol level and its relation to hospital mortality in AKI patients. Patients and methods This is a prospective, observational study that included 66 patients with AKI admitted to the Dialysis and Nephrology Unit, Mansoura University Hospital, who were assessed clinically, followed by cortisol level assay done at the day of admission. Patients were followed clinically and biochemically till discharge. Patients were classified according to random plasma cortisol level into two groups: group 1 included 14 patients with random plasma cortisol of less than 10 μg/dl (CIRCI group) and group 2 included 52 patients with random plasma cortisol of greater than or equal to 10 μg/dl. Results There was a significant increase in platelet count in group 1 compared with group 2, while there was a significant decrease in serum potassium level in group 1 compared with group 2. Moreover, there was a significant decrease in urine output volume in group 1 compared with group 2 (P=0.03). Finally the hospital mortality rate was significantly higher in group 1 (CIRCI group) compared with group 2 (P=0.004). Conclusion AKI patients with low cortisol level at admission have higher mortality rate during the hospitalization period.

Hypokalemia in Patients with COVID-19.

BackgroundPatients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19.MethodsA retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020.ResultsHypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3–3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%).Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36–4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08–3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228–1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170–1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222–1.047; P = 0.065) in our cohort of patients.ConclusionsHypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.Electronic supplementary materialThe online version of this article (10.1007/s10157-020-01996-4) contains supplementary material, which is available to authorized users.

Nephroprotective effect of Bacopa monnieri on gentamicin-induced nephrotoxicity in rodent models

Background: Drug-induced nephrotoxicity has been a significant cause of concern. Nephrotoxicity has been majorly implicated due to drug or toxin exposure. Bacopa monnieri commonly known, as “Brahmi,” is known to have a wide range of pharmacological principles responsible for various curative properties. Aim and Objective: The present study aims to assess the nephroprotective role of B. monnieri extract (BME) in gentamicin (GM)-induced nephrotoxic rodent model. Materials and Methods: Nephroprotective effect of the extract in doses of 100 mg/kg and 200 mg/kg was tested in GM-induced nephrotoxic rodent model. Mean kidney weight, urea, creatinine, blood urea nitrogen, and electrolytes were measured. Renal antioxidants were analyzed. Data were statistically analyzed. Results: Renoprotection in terms of reduced mean kidney weight, urea, creatinine, and blood urea nitrogen post-intoxication was observed maximum at dose of 200 mg/kg when compared with GM intoxicated group. Treatment with BME showed significant increase in serum sodium level and decrease in serum potassium level. Groups treated with BME showed significant increase in glutathione, superoxide dismutase, and catalase values at 100 mg/kg and 200 mg/kg. Conclusion: For progressive situations, nephroprotectant can be of utility. Promising results in terms of biochemical parameters were observed, where significant protection from renal injury can be postulated.

Effects of Sodium Bicarbonate in CKD Stages 3 and 4: A Randomized, Placebo-Controlled, Multicenter Clinical Trial

Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. Multicenter, randomized, placebo-controlled, clinical trial. 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. Initial mean serum bicarbonate level was in the normal range. Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. National Institutes of Health grant. Registered at ClinicalTrials.gov with study number NCT01452412.

Study of efficacy and safety of levosalbutamol versus racemic salbutamol delivered by metered dose inhaler in children with moderate persistent asthma

Aim: To compare the efficacy and safety of Levosalbutamol versus racemic Salbutamol delivered by metered dose inhaler in children with moderate persistent asthma. Materials and Methods: Children enrolled in the study were randomized to receive MDI Levosalbutamol 2 puff thrice daily, 50 µgm/puff (group A) or MDI Racemic Salbutamol 2 puff thrice daily. 100 µgm/puff (group B).Baseline characteristics of both groups were comparable. The FEV1 % and PEF % were assessed at baseline, at 15 minutes following the first dose on day 1 and on day 8. In children who remained symptomatic on day 8, an additional evaluation on day 15 was performed. Asthma symptom score were calculated from symptom score card. Results: There was significant improvement in PEF % and FEV1 % within each group. But there was no statistically significant inter-group difference in PEF % change and FEV1 % change except mean change in PEF % and ∆PEF % of initial on day 8 (at the end of 1 week).Asthma symptom score improved significantly in both groups but there was no inter group difference. Incidence of side effects like decrease in serum potassium level and increase in heart rate were comparable in between the two groups. Conclusion: Levosalbutamol administered via MDI improved PEF % significantly more in comparison of racemic Salbutamol after regular use of one week. However, no significant differences were observed in between the two drugs with respect to pulmonary function test on day 1, FEV1 % on day 8 and asthma symptom score. The side effect profile of the two drugs was comparable. This suggests that Levosalbutamol is at least as efficacious as conventional Salbutamol in terms of clinical efficacy.

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease.

BackgroundThe use of sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia lacks sufficient efficacy data in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD); however, use remains widespread. Recent evidence suggests that this population may be at risk for serious gastrointestinal adverse effects with SPS. Methods. We conducted a single-center retrospective cohort study. Adult patients with CKD Stages 4, 5, or ESRD maintained on renal replacement therapy with serum potassium >5 mEq/L and receipt of SPS were screened for inclusion. Our primary outcome was decrease in potassium within 24 h post-30 g oral SPS suspended in 33% sorbitol. Secondary outcomes included decrease in potassium within 24 h from 15 or 30 g SPS doses and gastrointestinal adverse events.ResultsOf 596 records, 114 were included for analysis. At the first serum potassium level within 24 h post-30 g oral SPS the median potassium decrease was 0.8 mEq/L [interquartile range (IQR) 0.4–1.1; P < 0.001]. At the first potassium level within 24 h post-15 or 30 g SPS, the median potassium decrease was 0.7 mEq/L (IQR 0.4–1.0; P < 0.001]. Post-SPS potassium levels occurred 14–16 h post-SPS. Gastrointestinal side effects occurred within 30 days of SPS in 5% of patients, although only two cases were classified as possibly associated.ConclusionsThe use of single-dose SPS monotherapy resulted in a significant decrease in serum potassium levels within 24 h in patients with CKD Stage 4, 5, or ESRD. However, it remains unclear if SPS is associated with an increased risk of gastrointestinal injury in this population.

High intake of orange juice and cola differently affects metabolic risk in healthy subjects

Higher consumption of sugar-containing beverages has been associated with an elevated risk of type 2 diabetes and gout. Whether this equally applies to cola with an unhealthy image and orange juice (OJ) having a healthy image remains unknown. In order to investigate whether OJ and cola differently affect metabolic risk 26 healthy adults (24.7±3.2y; BMI 23.2±3.3kg/m2) participated in a 2×2-wk intervention and consumed either OJ or caffeine-free cola (20% Ereq as sugar from beverages) in-between 3 meals/d at ad libitum energy intake. Glycemic control, uric acid metabolism and gut microbiota were assessed as outcome parameters. Fecal microbiota, body weight, basal and OGTT-derived insulin sensitivity remained unchanged in both intervention periods. Levels of uric acid were normal at baseline and did not change with 2-wk cola consumption (-0.03±0.67mg/dL; p>0.05), whereas they decreased with OJ intervention (-0.43±0.56mg/dL; p<0.01) due to increased uric acid excretion (+130.2±130.0mg/d; p<0.001). Compared to OJ, consumption of cola led to a higher daylong glycemia (ΔiAUC: 36.9±83.2; p<0.05), an increase in glucose variability (ΔMAGE-Index: 0.29±0.44; p<0.05), and a lower 24h-insulin secretion (ΔC-peptide excretion:-31.76±38.61μg/d; p<0.001), which may be explained by a decrease in serum potassium levels (-0.11±0.24mmol/L; p<0.05). Despite its sugar content, regular consumption of large amounts of OJ do not increase the risk of gout but may even contribute to lower uric acid levels. The etiology of impaired insulin secretion with cola consumption needs to be further investigated.

Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes.

Background/Aims:To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting.Methods:Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia.Results:A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia (< 3.5 mmol/L) was the most common type of electrolyte disturbance observed at 21.9%. A decrease in serum potassium levels was associated with decreases in blood glucose levels (r = 0.151, p = 0.025). During severe hypoglycemia, median blood glucose levels, incidence of tachycardia (> 100 beats per minute) and severe hypertension (≥ 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. Conclusions:During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

ImportanceHyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both.ObjectivesTo select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia.Design, Setting, and ParticipantsPhase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment.InterventionsPatients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower.Main Outcomes and MeasuresThe primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks.ResultsA total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients.Conclusions and RelevanceAmong patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks.Trial Registrationclinicaltrials.gov Identifier: NCT01371747

Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

BackgroundHyperkalemia increases the risk of death and limits the use of inhibitors of the renin–angiotensin–aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial.MethodsPatients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase.ResultsIn the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was −1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.ConclusionsIn patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939.)

抗微生物薬適正使用にかかわる薬学的介入；

The pharmacokinetics (PK)/pharmacodynamics (PD) theory has attracted attention in the treatment of infectious diseases. Drug concentrations and effects vary among patients for any given dose. A goal of population PK and PD is to identify patient-specific factors, such as weight, age, creatinine clearance (CCR), and disease and determine their associations with the observed PK/PD differences. Once associated with differences in drug concentrations or response, these distinguishing factors may then be used to better individualize drug therapy.This review summarizes our evaluation of the PK/PD analysis as follows:1)We investigated the compatibility of various carbapenem antibiotics with nafamostat mesilate for severe acute pancreatitis (SAP). Biapenem and doripenem, which exert their effects in a time-dependent manner, can be infused for prolonged periods for the treatment of SAP and other severe infections.2)The population PK on tazobactam/piperacillin (PIPC) was analyzed in Japanese patients with community-acquired pneumonia using the Nonlinear Mixed Effect Model version VI. Analysis using the one-compartment model yielded the following results for PIPC: total clearance (L/h) = 8.22 + (CCR - 71.4) × 0.0561, distribution volume (L) = 13.7.3)We found a positive relationship between the decrease in serum potassium levels and the liposomal Amphotericin B (L-AMB) dose. Logistic regression analysis of this relationship revealed that serum potassium levels tended to decrease on Days 5 to 6 of L-AMB administration.

Hypokalemic myoplegia

Acute generalized muscle weakness may have a different underlying cause. Among all urgently admitted patients, hypokalemia is observed in more than 20% of cases. Usually blood potassium concentration decrease is not fatal, but severe hypokalemia can be life-threatening for the patient suffering from cardiovascular diseases and respiratory disorders. Hypokalemia manifests clinically by muscle pain, weakness, the intestinal motility disorders, constipation, marked decrease in serum potassium levels can lead to fatal rhabdomyolysis. The key hormones that regulate the total stock of potassium in the body and its normal redistribution of intra- and extracellular fluid are insulin and catecholamines, interacting with β-adrenergic receptors. Regulation of blood potassium level is provided by insulin and it is a feedback (hyperkalemia stimulates insulin secretion, decreased potassium levels inhibits it). The level of catecholamines is not determined by potassium concentration, however, it influences the serum potassium level. Hypokalemia is usually the result of potassium loss due to abnormal renal (treatment with thiazides, high doses of corticosteroids, antibiotics, primary hyperaldosteronism due to adenoma, adrenal carcinoma, bilateral adrenal hyperplasia, Liddle, Bartter’s, Gitelman’s syndromes, 11β-hydroxysteroid dehydrogenase, 11β-hydroxylase, 17α-hydroxylase deficiency, Cushing’s syndrome) or extrarenal (intense vomiting, diarrhea due to excessive laxative use, salmonellosis, yersiniosis, HIV-infection, bowel tumors, chemotherapy, radiation therapy in cancer patients, celiac disease, jejunoileal bypass, a lack of potassium in food) potassium loss, an also a transmembrane shift of potassium (hypokalemic familial periodic paralysis, β2-agonist, bronchodilators, theophylline intake). Hypokalemic myoplegia may lead to fatal complications, requiring doctors of various specialties’ to know the clinical manifestations of hypokalemia, which may have different underlying cause.

Pretreatment of Formula or Expressed Breast Milk With Sodium Polystyrene Sulfonate (Kayexalate®) as a Treatment for Hyperkalemia in Infants With Acute or Chronic Renal Insufficiency

To evaluate the effect on serum potassium of treating infant formula or expressed breast milk (EBM) with sodium polystyrene sulfonate (SPS) before patient consumption. Retrospective cohort study of patients at Seattle Children's Hospital who received SPS-treated formula or EBM. Thirteen patients less than 2years of age with a diagnosis of hyperkalemia and acute kidney injury or chronic kidney disease that had received formula or EBM pretreated with SPS between September 2009 and May 2012 were identified. Hyperkalemia was defined as a serum potassium concentration greater than 5.5 mEq/L. The primary endpoint was the mean change in serum potassium 48hours after receiving pretreated formula or EBM. Serum potassium levels before and after patient consumption were averaged and compared using a paired t test. Pretreatment of formula or EBM with SPS resulted in a 24% decrease in serum potassium levels (6.3 mEq/L to 4.8 mEq/L; P< .0001). There was a significant difference in before and after calcium and creatinine levels (P < .05), and no significant differences in blood urea nitrogen, sodium, magnesium, phosphorus, chloride, or bicarbonate levels. Pretreatment of formula or EBM with SPS before consumption is an effective treatment for hyperkalemia in infants. Caution needs to be taken in patients who have sodium restrictions because the exchange for potassium produces a sodium-rich formula.

Transient decrease in serum potassium level during ischemic attack of acute coronary syndrome: Paradoxical contribution of plasma glucose level and glycohemoglobin

BackgroundAlthough a decrease in serum potassium level has been suggested to be a fairly common observation in acute coronary syndrome (ACS), there have so far been no definitive reports directly demonstrating the transient potassium decrease (the potassium dip) during ischemic attack of ACS compared to stable phase in individual patients. To understand the pathophysiological significance of the potassium dip, we examined the changes in serum potassium level throughout ischemic attack and evaluated the clinical factors affecting it.MethodsThe degree of the potassium dip during ischemic attack (as indicated by ΔK, ΔK = K at discharge − K on admission) was examined in 311 consecutive patients with ACS who required urgent hospitalization in our institution.ResultsSerum potassium level during ischemic attack was significantly decreased compared to that during stable phase (P < 0.001). Multiple regression analysis revealed that plasma glucose level during attack was the sole factor which was positively correlated with ΔK (P < 0.01), while HbA1c level was negatively correlated (P < 0.05). The medication profiles and renal function had no impact on ΔK. A longer hospitalization period, higher incidence of myocardial infarction and higher peak creatine kinase level were observed in patients with a larger ΔK.ConclusionsWe have clearly demonstrated that there is a transient decrease in serum potassium level during ischemic attack of ACS compared to stable phase. The degree of the potassium dip was tightly correlated with glucose level, which overwhelmed the diabetic condition, and it also indicates the disease severity. The present study therefore promotes awareness of the significance of monitoring potassium level in parallel with glucose level in patients with ACS.

High serum potassium levels after losartan can reflect more severe renal disease. Reply to Gonçalves AR, El Nahas AM [letter

High serum potassium levels after losartan can reflect more severe renal disease. Reply to Gonçalves AR, El Nahas AM [letter

Reducing the Incidence of Pseudohyperkalemia by Avoiding Making a Fist During Phlebotomy: A Quality Improvement Report

Pseudohyperkalemia is uncommon, but important. Local release of potassium caused by contraction of the forearm muscles from a tightly clenched fist or repeated fist clenching during phlebotomy is a recognized cause of pseudohyperkalemia. We investigated the use of a standard protocol to avoid fist clenching during phlebotomy. Quality improvement report. In 7 healthy volunteers, 10 blood samples were collected over 10-second intervals after 20 repeated fist clenching and unclenching movements. In 86 healthy volunteers, 3 blood samples were collected with and without prior fist clenching. Between September 1, 2006, and June 30, 2007, peripheral venous blood samples were collected from 73,846 outpatients at Chiba University Hospital without a protocol to avoid fist clenching. Between July 1, 2007, and March 31, 2009, blood samples were collected from 171,053 outpatients using the protocol. After July 1, 2007, blood samples were collected from the basilic or cephalic vein without making a fist or by making a fist using minimal gripping strength. Also, when multiple specimens were obtained from 1 patient, the specimen for measuring serum electrolytes was obtained after the other specimens. Pseudohyperkalemia, defined as unexplained serum potassium level ≥6.5 mmol/L. In the 7 volunteers, the decrease in serum potassium levels after cessation of fist clenching ranged from 8.4%-25.9%. In the 86 volunteers, the percentage with a decrease in serum potassium level ≥0.2 mmol/L between the first and third samples was 25.6% versus 6.7% with or without prior fist clenching, respectively. In clinical practice, we observed 8 cases of pseudohyperkalemia before implementing the protocol (0.0081%) and 1 case (0.00058%) after implementing the protocol (P = 0.001). Causes of hyperkalemia before using precautions were assessed using retrospective analyses. Avoiding fist clenching during phlebotomy and not using the first specimen for electrolyte measurements when obtaining multiple specimens from a single patient can reduce the occurrence of pseudohyperkalemia.