Low Serum Potassium Levels Research Articles

Abstract P156: Kidney Function and Serum Potassium as Predictors of Spironolactone Initiation in Congestive Heart Failure

Introduction: There are a paucity of data on real-world spironolactone use among patients with congestive heart failure (CHF), and whether spironolactone initiation differs by kidney function and serum potassium. Hypothesis: Patients with reduced kidney function and elevated serum potassium are less likely to be prescribed spironolactone than patients with normal kidney function and serum potassium. Methods: We identified patient cohorts with incident CHF and available laboratory data in the Truven MarketScan Commercial Claims and Encounters database (MS) from 2010-2015 (N=22,881), and the Geisinger Health System Integrated Electronic Health Record (GHS) from 2004-2016 (N=17,470), and assessed medication use through prescription order and dispensing data, and comorbidities using ICD codes. We measured incidence, initial dose, and duration of incident spironolactone use, overall and by levels of kidney function and serum potassium. We used Cox proportional hazards regression models to quantify the association between measures of baseline and time-varying estimated glomerular filtration rate (eGFR) and serum potassium, and incident spironolactone use, adjusting for other medication use and comorbidities. Results: Among 22,881 incident CHF patients in the MS database, mean age at CHF was 54.3 (±8.7) years, 47.2% were female, and the mean eGFR was 78.9 ml/min/1.73m 2 (±21). The 17,470 incident CHF patients in GHS were older (74.0 years ±12.9), more likely to be female (51.5%), and have a lower mean eGFR (62.5 ±24.3). Both cohorts had a mean baseline serum potassium of 4.3 mEq/L (±0.5). There were 1,341 (1,774) incident prescriptions for spironolactone over 34,384 (52,187) person-years in MS (GHS). Median starting dose was 25 mg in both cohorts. Women were less likely to start spironolactone in both cohorts, while older patients were less likely to start spironolactone only in GHS. Compared to patients with eGFR >90 ml/min/1.73m 2 , those with eGFR <30 ml/min/1.73m 2 were less likely to initiate spironolactone in MS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.38-0.84) and GHS (HR = 0.69, CI: 0.48-0.99). Patients with serum potassium <3.5 mEq/L were more likely to initiate spironolactone compared to those with 3.5-4.9 mEq/L (normal) in both cohorts (HR=1.99 [95% CI: 1.57-2.52] in MS; HR=2.70 [95% CI: 2.34-3.26] in GHS). Conclusion: Consistent with the labeled guidelines, patients with CHF and reduced kidney function were less likely to use spironolactone, while those with lower serum potassium levels were more likely to use spironolactone.

Electrolyte Disturbances in Acute Exacerbation of COPD

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. Acute exacerbation is an acute and sustained worsening of a patient’s condition from a stable state and it is associated with significant electrolyte disturbances.
 Objectives: The main objective of this study was to determine the prevalence of electrolyte disturbances in patients with acute exacerbation of COPD and to determine possible effects of these electrolyte disorders.
 Materials and Methods: This observational prospective study was carried out in the Department of Pulmonology, Enam Medical College & Hospital from 1st January to 31st December 2017. Sixty patients with acute exacerbation of COPD were included. Serum electrolytes and arterial blood gases were measured.
 Results: Low level of serum sodium (131 ± 5.66 mEq/L) and potassium (3.20 ± 0.44 mEq/L) were found in subjects with acute exacerbation of COPD. In patients with respiratory failure Na+ and K+ levels were even lower.
 Conclusion: Serum electrolytes in acute exacerbation of COPD patients should be monitored routinely and should be corrected early to avoid poor outcomes.
 J Enam Med Col 2019; 9(1): 25-29

Clinical and Etiological Spectrum of Hypokalemic Periodic Paralysis in a Tertiary Care Hospital in Pakistan.

IntroductionHypokalemic periodic paralysis (HPP) is characterized by muscle weakness secondary to low serum potassium levels. It may be primary in origin or there may be secondary causes like thyrotoxic periodic paralysis, renal or suprarenal causes, or non-renal causes like gastroenteritis.AimTo study the etiology, clinical manifestations, and outcome after therapy of patients with hypokalemic paralysis.MethodologyThe study was conducted from January 2016 to December 2016. Patients fulfilling the diagnostic criteria for hypokalemic paralysis, i.e., flaccid muscle weakness involving two or more limb muscles due to serum potassium < 3.5 mmol/L and with no objective sensory signs were included in the study. Relevant investigations were done. Those with other causes of flaccid weakness or on diuretic therapy were excluded from the study. Data was analyzed using SPSS Version 20.0 (IBM Corp., Armonk, NY).ResultsIn our study, 14 patients out of a total of 18 (14/18, i.e., 77.78%) were male and 4/18 (22.22%) were female [Male: Female ratio: 3.5:1]. The mean age of onset of HPP in males (29.5±10.14 yrs.) was lesser than that of females (41±10.8 yrs.), but this difference was statistically not significant (p<0.066). In the entire sample there were 15/18 cases (83.33%) of primary and 3/18 (16.67%) cases of secondary HPP [2/3 had thyrotoxic periodic paralysis and 1/3 had gastroenteritis]. Furthermore, 12/18 patients (66.66%) had symmetrical weakness (five cases of paraparesis and all were male; seven cases of quadriparesis: six males and one female) and 6/18 (33.33%) had asymmetrical weakness (two paraparesis: one male, one female; four quadriparesis: two males, two females). Statistically, no significant difference (p<0.709) was seen in those with symmetrical versus those with asymmetrical weakness. In this study 7/18 (38.89%) cases had absent, 1/18 (5.55%) had diminished, and 10/18 (55.55%) cases had intact deep tendon reflexes. None of the cases had cranial, bulbar, or respiratory involvement. The mean serum potassium of sample was 3.18±0.5 standard deviation (SD). The reduction in serum potassium was moderate (2.5-3.5 mmol/L) in primary and severe (<2.5 mmol/L) in secondary HPP. Those with quadriparesis had severe hypokalemia with a mean serum potassium of 2.1 mmol/L. Only 3/18 patients had concomitant magnesium deficiency. Patients given intravenous potassium replacement (except one with moderate hypokalemia and given oral replacement) recovered dramatically. The mean recovery time was 38.6±20.3 hours. The recovery time in quadriparesis was about 24 hours and in paraparesis was 12 hours. Only one patient with thyrotoxic periodic paralysis (TPP) and with severe serum potassium deficiency (0.9 meq/L) died due to cardiac arrhythmia. No atypical presentation was seen.ConclusionHPP has male preponderance. The age of onset of HPP is earlier in males than in females. Moreover, males are more prone to have symmetrical weakness. Asymmetrical weakness has almost an equal gender distribution. Primary hypokalemic paralysis is more frequent than secondary. Thyrotoxic periodic paralysis is the commonest cause of secondary periodic paralysis. The recovery time in quadriparesis is almost double the recovery time in paraparesis. Respiratory involvement is rare. HPP is an important differential in the diagnosis of acute flaccid muscle weakness. It should be promptly addressed to prevent recurrence of paralysis.

Sodium Zirconium Cyclosilicate: A Review in Hyperkalaemia.

Sodium zirconium cyclosilicate (Lokelma™) [hereafter referred to as SZC] is a non-absorbed, non-polymer zirconium silicate compound that preferentially exchanges hydrogen and sodium for potassium and ammonium ions in the gastrointestinal tract (GIT), thereby increasing faecal potassium excretion and lowering serum potassium levels. It is available as a powder for oral suspension (in water) and is approved in the EU and the USA for the treatment of hyperkalaemia in adults. In two multinational, phase III studies in adults with hyperkalaemia, SZC 10 g three times daily lowered serum potassium levels to within the normal range (3.5–5.0 mmol/L) during the first 48 h of treatment, and SZC 5 and 10 g once daily maintained normokalaemia over ≤ 28 days’ therapy. These beneficial effects were consistent across all patient subgroups (e.g. chronic kidney disease, diabetes, heart failure, concomitant use of RAAS inhibitor therapy), and appeared to be maintained over the longer term (≤ 12 months). SZC was generally well tolerated in adults with hyperkalaemia. Its tolerability profile was generally similar to that seen with placebo over ≤ 28 day, and its safety profile appeared to remain consistent over the longer term (≤ 12 months). Moreover, the incidence of hypokalemia was low. Current evidence indicates that SZC is a promising therapy for the management of hyperkalaemia in adults.

Association of Low Serum Potassium Levels and Risk for All-Cause Mortality in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Dyskalemia is a risk factor for mortality in patients without CKD, but the effect of hypokalemia in patients with CKD remains uncertain. PubMed, Embase, Cochrane, and Ovid databases were searched from inception to December 31, 2017 for studies that reported all-cause and cardiovascular mortality or events in patients with CKD (any stage). Pooled hazard ratios (HR) and corresponding 95% CI were calculated. A total of 11 clinical studies enrolling 57 234 subjects with CKD were included in the meta-analysis. Compared with control serum potassium (SK) levels, low SK (SK <4.0 mEq/L) was associated with higher risk of all-cause mortality in a random-effects model (HR = 1.57; 95% CI: 1.25-1.97). Moderate low SK (<3.5 mEq/L) increased risk of all-cause mortality by 105%. Mild low SK (3.5~4.0 mEq/L) also increased all-cause mortality risk (HR = 1.18, 95% CI: 1.11-1.26). Low SK was also associated with increased cardiovascular mortality (HR = 1.40, 95% CI: 1.22-1.62) and ESRD risk (HR = 1.35, 95% CI: 1.18-1.54). SK <4.0 mEq/L was associated with higher mortality risk in CKD patients, especially in those with SK <3.5 mEq/L. Additional prospective studies will be necessary to explore this relationship, as well as whether correcting hypokalemia decreases mortality in patients with CKD.

NEXT GENERATION SEQUENCING AND EXPERIMENTAL MYOLOGY: P.374Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing

Primary periodic paralysis comprises rare skeletal ion channelopathies characterized by recurrent quadriplegia typically associated with high or low serum potassium levels. We developed a gene panel that includes 10 ion channel-related genes and 245 muscular dystrophy- and myopathy-related genes and used this panel to diagnose 60 patients with primary periodic paralysis and identify the disease-causing or risk-associated gene mutations. The average sequencing depth using this panel was 488.11 ×, and the average coverage was 99.45%. Mutations in 5 genes were discovered in 40 patients (66.67%). Variants in SCN4A, KCNJ2 and CACNA1S genes accounted for 92.5% of the patients with a genetic diagnosis. SCN4A (NM_000334) mutations accounted for the majority in this primary PP cohort (47.5%). We identified 10 SCN4A variants including 5 reported mutations (c.2014C>T p.Arg672Cys, c.2024G>A p.Arg675Gln, c.2111C>T p.Thr704Met, c.4352G>T p.Arg1451Leu, and c.4774A>G p.Met1592Val) and 5 novel mutations (c.107_109del p.Glu36del, c.121C>T p.Arg41Trp, c.718G>A p.Val240Met, c.3868T>C p.Phe1290Leu and c.5293G>A p.Ala1765Thr). Among them, c.2024G>A p.Arg675Gln was identified in 8 patients from 6 families as a hotspot. KCNJ2 is the second most common genetic cause.We identified 9 reported variants (c.199C>T p.Arg67Trp, c.211G>A p.Asp71Asn, c.556C>A p.Pro186Thr, c.566G>T p.Arg189Ser, c.644G>A p.Gly215Asp, c.652C>T p.Arg218Trp, c. 899G>A p.Gly300Asp, c.919A>G p.Met307Val, and c.921G>C p.Met307Ile) in a total of 14 patients. Moreover, we identified 4 likely pathogenic variants (c.614T>A p.Phe205Tyr, c.1583G>A p.Arg528His, c.2965G>A p.Glu989Lys and c.3716G>A p.Arg1239His) in CACNA1S gene (NM_000069). Two RYR1 variants (p.Glu2764Lys and p.Ala4143Val) were identified in this cohort, together with one reported OPA1 variant (p.Ala357Thr) which is previously responsible for optic atrophy related phenotypes. Using targeted NGS, we achieved a diagnostic success rate of 66.67% in a cohort of primary PP patients. We expanded the spectrum of genotypes of primary PP and clinical phenotypes of known myopathy-related genes. We'd like to attribute this diagnostic rate to the inclusive strategy of screening for other causal factors of hypokalaemic muscle weakness and performing accurate clinical examinations and history inquiries prior to interpreting the NGS results.

Calcium-Polystyrene Sulfonate Decreases Inter-Dialytic Hyperkalemia in Patients Undergoing Maintenance Hemodialysis: A Prospective, Randomized, Crossover Study.

Hyperkalemia is a life-threatening emergency in maintenance hemodialysis (MHD) patients. This clinical trial investigated the efficacy and safety of calcium-polystyrene sulfonate (Ca-PS) in MHD patients with interdialytic hyperkalemia. A total of 58 hemodialysis patients with hyperkalemia (≥5.5 mol/L) were selected and administered either a 3-week Ca-PS (3 × 5 g/day) or a blank control following the model of a prospective, randomized, crossover clinical trial with a 1-week washout period. All patients were followed up for another 3 weeks for safety evaluations. The primary outcome was the magnitude of the change in serum potassium levels. The secondary outcomes were electrocardiography (ECG) changes and treatment safety (volume overload, electrolyte imbalance). Compared with the control group, Ca-PS treatment significantly reduced serum potassium levels (P <0.01). More patients in the Ca-PS group had lower serum potassium levels than the safety level of <5.5 mmol/L (32% for control vs. 61% for Ca-PS, P <0.01). Peaked T-wave occurred less frequently in patients in the Ca-PS group (13.8% for Ca-PS vs. 31.03% for control, P <0.01). In addition, Ca-PS reduced serum phosphorus levels with no effects on serum levels of calcium and sodium, fluid volume, blood pressure, or interdialytic weight gain. Ca-PS treatment decreases serum levels of potassium and phosphorus in MHD patients with interdialytic hyperkalemia. Ca-PS does not induce volume overload or disrupt electrolyte balance.

Knockout of Kcnj16 (Kir5.1) in Dahl Salt‐Sensitive Rats Produces Seizure Phenotype

Kir5.1 is a member of an inwardly rectifying potassium (Kir) channel family notably present in the kidney and brain. We previously established that a knockout rat model of Kcnj16 (gene encoding Kir5.1) on a Dahl salt‐sensitive background (SSKcnj16−/−) exhibits a severe cardiovascular phenotype (Palygin et al., JCI Insight, 2017). Mutations in ion channel genes can alter neuronal excitability and mutations in Kir genes have been linked to seizure disorders in humans. Since Kir5.1 is known to be expressed in the brain and may contribute to neuronal membrane potential and spatial potassium buffering, we hypothesized that in addition to cardiovascular and renal dysfunction, neurological phenotypes, including seizures, would be prevalent in the SSKcnj16−/−rats. We found that SSKcnj16−/− rats (but not control SS rats) experience tonic‐clonic seizures when exposed to a 10 kHz tone (86 dB for 2 min), whereas other frequencies (0.1 or 1 kHz) did not elicit seizures. When exposed to the seizure‐inducing acoustic stimulus once/day for 10 days, we noted that SSKcnj16−/− rats experienced a seizure in response to 92% of stimuli. SSKcnj16−/− rats also showed spontaneous mortality within hours after a stimulus with a survival rate of 67% (N=21) for the duration of the 10 day protocol. Control rats (N=10) had no incidence of seizure or death during the 10 days of acoustic stimulation. We found no difference among male and female SSKcnj16−/− rats, where both sexes had a similar audiogenic seizure response and reduced survival. Behavioral tests including a modified Irwin screen and open field test revealed that before and after seizure stimulation SSKcnj16−/− rats tended to have altered activity levels, gait, piloerection, and respiration rates. Analysis of blood electrolytes revealed critically low serum potassium levels in SSKcnj16−/− compared to SS controls, a difference that appeared to be exacerbated by repeated seizures. We hypothesize that seizures may be intensifying potassium imbalance and disrupting the homeostasis that is particularly essential for excitable cells such as neurons. We conclude that knockout of Kir5.1 leads to distinct neurological phenotypes including a seizure disorder and subsequent spontaneous death, which may have relevance to channelopathies associated with seizure disorders in humans.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20–65 years of age and plasma creatinine 100–220 μmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27–61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8–75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.

Aldosterone induces left ventricular subclinical systolic dysfunction: a strain imaging study.

Primary aldosteronism is associated with a higher incidence of left ventricular (LV) hypertrophy and diastolic dysfunction than essential hypertension. However, systolic function via endocardial measurements is similar between patients with primary aldosteronism and essential hypertension. Speckle-tracking echocardiography is a sensitive tool which can detect subclinical impairments in systolic function. The aim of this study was to investigate aldosterone-induced subclinical impairments in systolic function. We prospectively enrolled patients with primary aldosteronism and essential hypertension and analyzed their clinical data, biochemical data, and echocardiographic parameters, including myocardial strain [global longitudinal strain (GLS)]. Thirty-six patients with primary aldosteronism and 31 patients with essential hypertension were enrolled for analysis. The patients with primary aldosteronism had significantly lower serum potassium levels, lower plasma renin activity, higher aldosterone-to-renin ratio (ARR), and higher 24-h urinary aldosterone levels than patients with essential hypertension. With regards to echocardiographic parameters, the patients with primary aldosteronism had a thicker ventricular wall and higher LV mass index than those with essential hypertension. Most importantly, we found significant degradation of GLS in the patients with primary aldosteronism compared with those with essential hypertension (-17.84 ± 2.36 vs. -20.13 ± 2.32, P < 0.001). In correlation analysis, GLS was significantly correlated with serum potassium level, LV mass index, log-transformed plasma renin activity, log-transformed ARR, and log-transformed 24-h urinary aldosterone levels (all P < 0.05). Multivariate linear regression analysis further identified log-transformed ARR (β = 0.771, 95% confidence interval: 0.011-1.530, P = 0.047), and log-transformed 24-h urinary aldosterone level (β = 1.765, 95% confidence interval: 0.01-3.529, P = 0.050) as independent factors correlated with GLS. Patients with primary aldosteronism have a lower magnitude of GLS than patients with essential hypertension, suggesting that aldosterone induces a subclinical decline in LV systolic function.

Is it time to rethink about protocols for managing intraoperative serum potassium and blood glucose levels during off-pump coronary artery bypass surgery?

Background A low perioperative serum potassium level ( 200 mg/dl) during cardiac surgery is a preventable cause of high morbidity and mortality. In this study, we measured the changes in intraoperative levels of serum potassium and blood glucose in adult patients undergoing elective off-pump coronary artery bypass (OPCAB) surgery, while administering insulin intraoperatively as per the present guidelines. Patients and methods Thirty-six adults, aged 18–65 years, undergoing elective OPCAB surgery were enrolled in this study. Arterial blood gas analysis was performed at predetermined intraoperative time points to measure serum potassium and blood glucose levels as primary variables. Base excess, pH, and HCO3− were recorded as secondary variables. Insulin infusion was started according to the sliding scale, whenever blood glucose was more than 180 mg/dl. Intravenous potassium was supplemented, when serum potassium was less than 4 mEq/l. Quantitative variables were compared with baseline using paired t test and repeated measure analysis of variance was used for comparison across follow up. Results Potassium chloride had to be continuously administered intravenous to maintain serum potassium levels more than 4 mEq/l throughout OPCAB surgery. There was a highly significant (P Conclusion Patients are prone to hypokalemia and hyperglycemia during OPCAB surgery, despite following the current guidelines. More studies are needed to formulate a better insulin infusion protocol for maintaining normoglycemia and guidelines need to be formulated for continuous intraoperative potassium infusion during OPCAB surgery.

Scorpion envenoming in Morona Santiago, Amazonian Ecuador: Molecular phylogenetics confirms involvement of the Tityus obscurus group

Scorpion envenoming by species in the genus Tityus is hereby reported from rural locations in the Amazonian province of Morona Santiago, southeastern Ecuador. Twenty envenoming cases (18 patients under 15 years of age) including one death (a 4-year-old male) were recorded at the Macas General Hospital, Morona Santiago, between January 2015 and December 2016 from the counties of Taisha (n=17), Huamboyo (n=1), Palora (n=1), and Logroño (n=1). An additional fatality from 2014 (a 3-year-old female from Nayantza, Taisha county) is also reported. Leukocytosis and low serum potassium levels were detected in most patients. We observed a significant negative correlation between leukocytosis and hypokalemia. Scorpions involved in three accidents from Macuma, Taisha County, were identified as genetically related to Tityus obscurus from the Brazilian Amazonian region based on comparison of mitochondrial DNA sequences encoding cytochrome oxidase subunit I. These cases, along with previously reported envenoming from northern Manabí, reinforce the notion that scorpionism is a health hazard for children in Ecuador and emphasizes the need to supply effective antivenoms against local species, which are not currently available. The genetic affinity of the Ecuadorian specimens with T. obscurus may underlay toxinological, clinical, and venom antigenic relationships among Amazonian scorpions that deserves further exploration for designing therapeutic strategies to treat scorpionism in the region.

Giving Is Nursing.

Giving Is Nursing.

Intra-dialytic hypertension is associated with high mortality in hemodialysis patients.

BackgroundIntra-dialytic hypertension (IDH) is emerging as an important issue in hemodialysis patients. Its risk factors and clinical outcomes are unclear.MethodsA total of 73 prevalent hemodialysis patients were enrolled. They included 14 (19.2%) patients with baseline IDH and 59 patients without IDH. Their clinical parameters, laboratory parameters, and mortality were investigated over 78 months.ResultsThe risks factor of IDH included low serum potassium levels, low ultrafiltration, and low arm muscle area. Lower median survival was evident in the IDH group compared to the non-IDH group, but was not significantly different. After adjusting for relevant confounders for age, the IDH group displayed 2.846 times higher mortality rate than the non-IDH Group (adjusted hazard ratio: 2.846; 95% confidence interval: 1.081–7.490; P = 0.034).ConclusionIDH is associated with high mortality in hemodialysis patients. Clinicians should be aware of the risk factors. Future research studies are needed to explore the mechanisms involved in the association between IDH and mortality.

Voriconazole-induced QT prolongation among hemato-oncologic patients: clinical characteristics and risk factors.

The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole. We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications. Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0±52.9msec) was significantly longer compared to QTc off voriconazole (421.8±42.2msec; p=0.002). QTcP ≥30msec and ≥60msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc≥450msec (upper QTc quartile) (p<0.01) and low serum potassium levels (p<0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP. Our findings indicate that hemato-oncologic patients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc≥450msec and low serum potassium levels.

Race, Serum Potassium, and Associations With ESRD and Mortality

Recent studies suggest that potassium levels may differ by race. The basis for these differences and whether associations between potassium levels and adverse outcomes differ by race are unknown. Observational study. Associations between race and potassium level and the interaction of race and potassium level with outcomes were investigated in the Racial and Cardiovascular Risk Anomalies in Chronic Kidney Disease (RCAV) Study, a cohort of US veterans (N=2,662,462). Associations between African ancestry and potassium level were investigated in African Americans in the Atherosclerosis Risk in Communities (ARIC) Study (N=3,450). Race (African American vs non-African American and percent African ancestry) for cross-sectional analysis; serum potassium level for longitudinal analysis. Potassium level for cross-sectional analysis; mortality and end-stage renal disease for longitudinal analysis. The RCAV cohort was 18% African American (N=470,985). Potassium levels on average were 0.162mmol/L lower in African Americans compared with non-African Americans, with differences persisting after adjustment for demographics, comorbid conditions, and potassium-altering medication use. In the ARIC Study, higher African ancestry was related to lower potassium levels (-0.027mmol/L per each 10% African ancestry). In both race groups, higher and lower potassium levels were associated with mortality. Compared to potassium level of 4.2mmol/L, mortality risk associated with lower potassium levels was lower in African Americans versus non-African Americans, whereas mortality risk associated with higher levels was slightly greater. Risk relationships between potassium and end-stage renal disease were weaker, with no difference by race. No data for potassium intake. African Americans had slightly lower serum potassium levels than non-African Americans. Consistent associations between potassium levels and percent African ancestry may suggest a genetic component to these differences. Higher and lower serum potassium levels were associated with mortality in both racial groups.

Lower serum potassium associated with increased mortality in dialysis patients: A nationwide prospective observational cohort study in Korea.

BackgroundAbnormal serum potassium concentration has been suggested as a risk factor for mortality in patients undergoing dialysis patients. We investigated the impact of serum potassium levels on survival according to dialysis modality.MethodsA nationwide, prospective, observational cohort study for end stage renal disease patients has been ongoing in Korea since August 2008. Our analysis included patients whose records contained data regarding serum potassium levels. The relationship between serum potassium and mortality was analyzed using competing risk regression.ResultsA total of 3,230 patients undergoing hemodialysis (HD, 64.3%) or peritoneal dialysis (PD, 35.7%) were included. The serum potassium level was significantly lower (P < 0.001) in PD (median, 4.5 mmol/L; interquartile range, 4.0–4.9 mmol/L) than in HD patients (median, 4.9 mmol/L; interquartile range, 4.5–5.4 mmol/L). During 4.4 ± 1.7 years of follow-up, 751 patients (23.3%) died, mainly from cardiovascular events (n = 179) and infection (n = 120). In overall, lower serum potassium level less than 4.5 mmol/L was an independent risk factor for mortality after adjusting for age, comorbidities, and nutritional status (sub-distribution hazard ratio, 1.30; 95% confidence interval 1.10–1.53; P = 0.002). HD patients showed a U-shaped survival pattern, suggesting that both lower and higher potassium levels were deleterious, although insignificant. However, in PD patients, only lower serum potassium level (<4.5 mmol/L) was an independent predictor of mortality (sub-distribution hazard ratio, 1.35; 95% confidence interval 1.00–1.80; P = 0.048).ConclusionLower serum potassium levels (<4.5 mmol/L) occur more commonly in PD than in HD patients. It represents an independent predictor of survival in overall dialysis, especially in PD patients. Therefore, management of dialysis patients should focus especially on reducing the risk of hypokalemia, not only that of hyperkalemia.

Novel lincRNA Susceptibility Gene and Its Role in Etiopathogenesis of Thyrotoxic Periodic Paralysis.

Thyrotoxic periodic paralysis (TPP) is a life-threatening neuromuscular complication of thyrotoxicosis characterized by muscle weakness and hypokalemia and with an unclear etiopathogenesis. However, the 17q24.3 locus had been genetically linked to TPP, in which the genetic variant rs312691 (TC genotype) in long intergenic noncoding RNA (lincRNA) CTD-2378E21.1 is located downstream of inward-rectifier potassium (Kir) channel genes [KCNJ2 and its antisense KCNJ2 (AS-KCNJ2)]. A TPP patient with a suppressed thyroid-stimulating hormone level, a high free thyroxine level of (5.8 ng/dL), and low serum potassium level of (2 mEq/L) was evaluated for Kir channel expression during and after recovery from thyrotoxicosis. We observed that circulating lincRNA and Kir expression varied in accordance with thyroid status and TC genotype. To endorse this association of a lincRNA-rs312691 variant with a genetic risk of TPP, an additional series of 37 patients with TPP and 32 patients with thyrotoxic without paralysis (TWP) were assessed. We verified that the risk of minor allele C was greater in TPP than in TWP (odds ratio, 5.289; P = 0.0062), and protective major allele T was more frequent than observed in the 1000 genome controls (odds ratio, 11.90; P < 0.0001). AS-KCNJ2 was downregulated during thyrotoxicosis in the TWP controls carrying allele T and were upregulated in those with TPP with risk allele C. Moreover, KCNJ2 (Kir2.1) expression was reduced during thyrotoxicosis and restored in euthyroid status. We further excluded any other coding variant by performing targeted exome sequencing mutational screening in 17q24.3. Our data suggest that high lincRNA AS-KCNJ2 and CDT-2378E21.1 expression, possibly driven by the triiodothyronine regulatory mechanism, reduces the Kir2.1 expression observed during thyrotoxicosis. This finding could contribute to the understanding of the reduced inward-rectifying current observed during muscle weakness in genetically susceptible TPP patients.

Post-Saline Infusion Plasma Aldosterone Concentrations are Well Correlated with the Lateralized Ratio of Adrenal Venous Sampling in Patients of Primary Aldosteronism

Objective: Adrenal venous sampling (AVS) is the most reliable test to distinguish between unilateral and bilateral primary aldosteronism (PA). However, AVS is invasive, risky, and expensive, and alternative diagnostic methods are desirable. This study aimed to investigate the diagnostic power of saline infusion test (SIT) to distinguish between unilateral and bilateral PA. Design: Retrospective database analysis. Subjects and Methods: We selected 111 patients with PA diagnosed by confirmatory tests who underwent both SIT and successful AVS. Thirty-two patients had lateralized ratio (LR) over 4.0 and 79 patients had LR less than 4.0. Multiple regression analysis and receiver operating characteristic (ROC) analysis were used to examine whether the SIT had good diagnostic power to distinguish between patients with high LR and those with low LR. Results: The patients with high LR had significantly lower serum potassium levels (P<0.0001, Mann-Whitney’s U Test) and higher plasma aldosterone concentrations after SIT (Post-PAC) (P<0.0001). It was revealed that Post-PAC levels were independently associated with the LR by multiple regression analysis (P=0.0112). ROC analysis revealed that the diagnostic accuracy of SIT was very high for distinguishing between patients with high LR and those with low LR. The optimal cut-off value of Post-PAC for the diagnosis of patients with low LR was less than 9.3 ng/dl. Conclusions: SIT is useful for distinguishing between patients with high LR and low LR. It might be possible to omit AVS in patients with a Post-PAC value less than 9.3 ng/dl.Combining the results of serum potassium levels and imaging examinations with SIT might be a potential strategy for PA subtypes.

Modeling the effectiveness of nebulized terbutaline for decompensated chronic obstructive pulmonary disease patients in the emergency department.

Short-acting β2-agonists (SABA) are widely used in the emergency department (ED) to treat patients with decompensated chronic obstructive pulmonary disease (COPD). We sought to model the effectiveness of nebulized SABA (terbutaline) on clinically relevant parameters associated with a reduction in work of breathing or respiratory muscle fatigue in decompensated COPD patients admitted to the ED.Forty consecutive decompensated COPD patients (having received at least one dose of nebulized terbutaline during their stay in the ED) were included in an observational cohort study. The terbutaline dose received at time t was expressed as cumulative dose and as a rate (mg/day). The associations between the terbutaline dose and time-dependent outcome parameters (respiratory rate, heart rate, arterial blood gases, and, as a marker of terbutaline's systemic effect, serum potassium) were analyzed using a nonlinear, mixed-effects model. The effect of various covariates influencing terbutaline's effectiveness (baseline characteristics and concomitant treatments) was assessed on the model.Among the investigated patients, a total of 377 time-dependent observations were available for analysis. Neither the cumulative dose nor the dose rate at time t significantly influenced the arterial blood gas parameters or heart rate. The cumulative dose of terbutaline was associated with a lower serum potassium level (P < 0.001) and, less significantly, a lower respiratory frequency (P = 0.036). In a tertile analysis, the need for post-ED hospitalization was not associated with the cumulative dose or dose rate of terbutaline.Overall, the results of our modeling study strongly suggest that terbutaline dose did not influence time-dependent outcomes other than serum potassium, and thus call into question the systematic administration of inhaled SABA to patients admitted to the ED for decompensated COPD.