Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO-DKD and FIDELIO-DKD.

AIMS: To perform dose-exposure-response analyses to determine the effects of finerenone doses. MATERIALS AND METHODS: Two randomized, double-blind, placebo-controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m2 , a urine albumin-creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.8 mmol/L were included. Interventions were titrated doses of finerenone 10 or 20 mg versus placebo on top of standard of care. The outcomes were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR and kidney composite outcomes, assessed using nonlinear mixed-effects population pharmacokinetic (PK)/pharmacodynamic (PD) and parametric time-to-event models. RESULTS: For potassium, lower serum levels and lower rates of hyperkalaemia were associated with higher doses of finerenone 20 mg compared to 10 mg (p < 0.001). The PK/PD model analysis linked this observed inverse association to potassium-guided dose titration. Simulations of a hypothetical trial with constant finerenone doses revealed a shallow but increasing exposure-potassium response relationship. Similarly, increasing finerenone exposures led to less than dose-proportional increasing reductions in modelled UACR. Modelled UACR explained 95% of finerenone's treatment effect in slowing chronic eGFR decline. No UACR-independent finerenone effects were identified. Neither sodium-glucose cotransporter-2 (SGLT2) inhibitor nor glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment significantly modified the effects of finerenone in reducing UACR and eGFR decline. Modelled eGFR explained 87% of finerenone's treatment effect on kidney outcomes. No eGFR-independent effects were identified. CONCLUSIONS: The analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations. UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone's kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP-1RAs.

Seasonal variation of serum potassium in hemodialysis patients: myth or reality? A narrative review of literature.

Research has shown that patients undergoing hemodialysis experience seasonal variations in their serum potassium levels. There was inconsistent seasonal fluctuation in serum potassium levels among the hemodialysis population across different locations. In the form of narrative review for the first time, the article discusses the seasonal changes of serum potassium in this population and its potential reasons, this article demonstrates that it is primarily attributable to seasonal dietary potassium intake. However, existing studies have not quantified seasonal dietary potassium intake, so the results are still speculative. Furthermore, future research ought to further expound upon the clinical implications of seasonal variations in serum potassium levels among dialysis patients, as well as other influencing mechanisms such as the pathophysiological causes of these seasonal changes, particularly those pertaining to dietary, geographical, and regional factors. These findings contribute to a more thorough interpretation of laboratory results in hemodialysis patients and provide important guidance for their individualized dietary management.

Serum Potassium Levels and Mortality in Hospitalized Heart Failure Patients.

Background: To assess the link between serum potassium ( K + ) and all-cause mortality in hospitalized heart failure (HF) patients. Methods: Hospitalized HF patients (n = 3114) were analyzed at the Fuwai Hospital Heart Failure Center. Before discharge, HF patients were divided into four groups according to the K + level quartiles: K + ≤ 3.96 mmol/L (Q1), 3.96 < K + ≤ 4.22 mmol/L (Q2), 4.22 < K + ≤ 4.52 mmol/L (Q3), and K + > 4.52 mmol/L (Q4). At 90 days, 2 years, and maximal follow-up, all-cause mortality was the primary outcome. Results: Patients with HF in the Q4 group had worse cardiac function, higher N-terminal pro-B-type natriuretic peptide levels, lower left ventricular ejection fractions and lower estimated glomerular filtration rates than patients in the Q2 group. In the multivariate-adjusted Cox analysis, the mortality assessed during the 90-day, 2-year, and maximal follow-up examinations increased in the Q4 group of HF patients but not in the Q1 and Q3 groups. The Q4 group had a 28% (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.09-1.49, p = 0.002) higher risk of all-cause mortality at maximum follow-up. Hypokalemia and hyperkalemia were linked to increased HF mortality risk at the 90-day, 2-year, and maximal follow-up periods. Conclusions: Serum K + levels had a J-shaped association with all-cause mortality in HF patients. Both hypokalemia and a K + level of > 4.52 mmol/L were associated with increased all-cause mortality in the short term and long term, suggesting a narrow target K + range in HF patients. Clinical Trial Registration: Unique Identifier: NCT02664818; URL: clinicaltrials.gov.

Epidemiology, prognosis and management of potassium disorders in Covid-19.

Coronavirus disease (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre-existing comorbidities and laboratory parameters such as white blood cell count, D-dimer, C-reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid-19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid-19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid-19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.

Serum glucose/potassium ratio as a clinical risk factor for predicting the severity and prognosis of acute traumatic spinal cord injury.

OBJECTIVE: Acute traumatic Spinal cord injury (TSCI) is a devastating event that causes severe sensory and motor impairments as well as autonomic dysfunction in patients, yet relevant clinical biomarkers have not been established. This study aimed to determine the significance of the serum glucose/potassium ratio (GPR) in evaluating TSCI severity and predicting prognosis. METHODS: An analysis of 520 clinical records of acute TSCI patients from January 2012 to June 2022 was conducted. The relationships between serum GPR and The American Spinal Injury Association Impairment Scale (AIS) grade 6-month post-trauma prognosis and the admission AIS grade were analyzed. To evaluate the discriminatory ability, a receiver operating characteristic curve (ROC) analysis was used. All methods were performed in accordance with the relevant guidelines and regulations. RESULTS: Based on the initial assessment of AIS grade, 256 (49.2%) patients were categorized into the severe TSCI group (AIS A-B), and there was a significant correlation between the severe TSCI group and serum GPR (p < 0.001). Serum GPR was reduced in an AIS grade-dependent manner (R = - 0.540, p < 0.001). Of the 520 patients, 262 (50.4%) patients were classified as having a poor prognosis according to the AIS grade at discharge. Serum GPR was also reduced in an AIS grade at discharge-dependent manner (R = - 0.599, p < 0.001), and was significantly higher in the poor prognosis group compared to the good prognosis group (p < 0.001). Poor prognosis was significantly associated with sex (p = 0.009), severity of TSCI (p < 0.001), location of TSCI (p < 0.001), surgical decompression (p < 0.018), body temperature (p < 0.001), heart rate (p < 0.001), systolic arterial pressure (SAP) (p < 0.001), diastolic arterial pressure (DAP) (p < 0.001), serum GPR (p < 0.001), serum glucose (p < 0.001), serum potassium (p < 0.001), and white blood cell count (p = 0.003). Multivariate logistic regression analysis showed a significant correlation between poor prognosis and serum GPR (p = 0.023). The ROC analysis showed the area under the curve of serum GPR to be a poor predictor of prognosis in TSCI patients at 0.842 (95% confidence interval, 0.808-0.875). CONCLUSION: There was a significant relationship between serum GPR and admission injury severity and the 6-month prognosis of acute TSCI patients. Serum GPR serves as a readily available clinical risk factor for predicting the severity and 6-month prognosis of acute traumatic spinal cord injury, which holds potential clinical significance for patients with TSCI.

Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypokalemia is a common electrolyte abnormality in patients on peritoneal dialysis (PD) and has been associated with increased risks of peritonitis and death. Whether correction of hypokalemia improves these outcomes is unknown. STUDY DESIGN: Multicenter, open-label, prospective, randomized controlled trial. SETTING & PARTICIPANTS: Adult (aged ≥18 years) PD patients with hypokalemia (defined as at least 3 values or an average value <3.5 mEq/L in the past 6 months). Randomization was stratified according to center and residual urine output (≤100 or >100 mL/day). INTERVENTIONS: Random assignment to either protocol-based potassium supplementation (titratable dose of oral potassium chloride to maintain serum potassium of 4-5 mEq/L) or conventional potassium supplementation (reactive supplementation when serum potassium is <3.5 mEq/L) over 52 weeks. Treatment groups were compared using intention-to-treat analyses implemented using Cox proportional hazards regression. OUTCOME: The primary outcome was time from randomization to first peritonitis episode (any organism). Secondary outcomes were all-cause mortality, cardiovascular mortality, hospitalization, and conversion to hemodialysis. RESULTS: A total of 167 patients with time-averaged serum potassium concentrations of 3.33 ± 0.28 mEq/L were enrolled from 6 PD centers: 85 were assigned to receive protocol-based treatment, and 82 were assigned to conventional treatment. The median follow-up time was 401 (IQR, 315-417) days. During the study period, serum potassium levels in the protocol-based treatment group increased to 4.36 ± 0.70 mEq/L compared with 3.57 ± 0.65 mEq/L in the group treated conventionally (mean difference, 0.66 [95% CI, 0.53-0.79] mEq/L; P < 0.001). The median time to first peritonitis episode was significantly longer in the protocol-based group (223 [IQR, 147-247] vs 133 [IQR, 41-197] days, P = 0.03). Compared with conventional treatment, the protocol-based group had a significantly lower hazard of peritonitis (HR, 0.47 [95% CI, 0.24-0.93]) but did not differ significantly with respect to any of the secondary outcomes. Asymptomatic hyperkalemia (>6 mEq/L) without characteristic electrocardiographic changes occurred in 3 patients (4%) in the protocol-based treatment group. LIMITATIONS: Not double-masked. CONCLUSIONS: Compared with reactive potassium supplementation when the serum potassium level falls below 3.5 mEq/L, protocol-based oral potassium treatment to maintain a serum potassium concentration in the range of 4-5 mEq/L may reduce the risk of peritonitis in patients receiving PD who have hypokalemia. TRIAL REGISTRATION: Registered at the Thai Clinical Trials Registry with study number TCTR20190725004.

Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Renin-angiotensin-aldosterone system (RAAS) inhibitors are evidence-based therapies that slow the progression of chronic kidney disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAAS inhibitors after an episode of hyperkalemia and clinical outcomes in patients with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba (7,200) and Ontario (n = 71,290), Canada, with an episode of de novo RAAS inhibitor-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD. EXPOSURE: RAAS inhibitor prescription. OUTCOME: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and nonfatal CV events, dialysis initiation, and a negative control outcome (cataract surgery). ANALYTICAL APPROACH: Cox proportional hazards models examined the association of RAAS inhibitor continuation (vs discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity-matched analyses. RESULTS: The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 m2, respectively, in Manitoba; and 5.7 mEq/L and 41 mL/min/1.73 m2, respectively, in Ontario. RAAS inhibitor discontinuation was associated with a higher risk of all-cause mortality (Manitoba: HR, 1.32 [95% CI, 1.22-1.41]; Ontario: HR, 1.47 [95% CI, 1.41-1.52]) and CV mortality (Manitoba: HR, 1.28 [95% CI, 1.13-1.44]; and Ontario: HR, 1.32 [95% CI, 1.25-1.39]). RAAS inhibitor discontinuation was associated with an increased risk of dialysis initiation in both cohorts (Manitoba: HR, 1.65 [95% CI, 1.41-1.85]; Ontario: HR, 1.11 [95% CI, 1.08-1.16]). LIMITATIONS: Retrospective study and residual confounding. CONCLUSIONS: RAAS inhibitor discontinuation is associated with higher mortality and CV events compared with continuation among patients with hyperkalemia and CKD. Strategies to maintain RAAS inhibitor treatment after an episode of hyperkalemia may improve clinical outcomes in the CKD population.

Association of Serum Potassium Levels with Mortality and Cardiovascular Events: Findings from the Chinese Multi-provincial Cohort Study.

BACKGROUND: Dyskalemia involves critical electrolyte abnormalities and increases mortality risk in patients with acute clinical conditions. However, the association between dyskalemia and adverse outcomes in the general population is less well established. OBJECTIVE: To investigate the association of serum potassium levels with mortality and cardiovascular events in the general population and to explore the characteristics of individuals at high risk. DESIGN: A prospective cohort study. PARTICIPANTS: A total of 5220 participants aged 50-79 years in the Chinese Multi-provincial Cohort Study. MAIN MEASURES: Serum potassium levels were measured by the ion-selective electrode method. The outcomes were incident cardiovascular disease (CVD), CVD death, non-CVD death, and total death. KEY RESULTS: Of the 5220 participants, 48.2% were men, and the mean age was 62.3 (SD 7.6) years. Hyperkalemia was found in 8.7% of the participants and was significantly associated with total death (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.18-2.23) and CVD death (HR, 2.12; 95% CI, 1.25-3.61) after adjustment. Furthermore, the HRs (95% CIs) of hyperkalemia combined with 2 and ≥ 3 risk factors were 2.37 (1.50-3.74) and 4.06 (2.37-6.95) for total death and 3.26 (1.56-6.80) and 8.42 (4.06-17.50) for CVD death, respectively. The 10-year cumulative incidence of total death was 17.4% for participants with 2 or more risk factors. CONCLUSION: Hyperkalemia is associated with an increased risk of all-cause and CVD death, and this risk is more pronounced in patients with multiple risk factors. Our findings suggest that early identification and management of hyperkalemia in the general population are warranted.

Potassium and fiber: a controversial couple in the nutritional management of children with chronic kidney disease.

BACKGROUND: Fruit and vegetable intake is commonly discouraged in children with chronic kidney disease (CKD) to avoid hyperkalemia. However, direct evidence in support of this widespread practice is lacking. Furthermore, the resultant restricted fiber exposure may deprive CKD patients from potential health benefits associated with the latter. Therefore, we investigated associations between dietary potassium intake, fiber intake, and serum potassium levels in pediatric CKD. METHODS: This study is a longitudinal analysis of a 2-year, prospective, multi-institutional study, following children with CKD at 3-month intervals. At each visit, dietary potassium and fiber intake were assessed, using 24-h recalls and 3-day food records. On the same occasion, serum potassium concentrations were determined. Associations between dietary potassium intake, dietary fiber intake, and serum potassium concentrations were determined using linear mixed models. RESULTS: Fifty-two CKD patients (7 transplant recipients, none on dialysis) aged 9 [4;14] years with an estimated glomerular filtration rate (eGFR) of 49 [25;68] mL/min/1.73 m2 were included. For every g/day decrease in dietary potassium intake, the estimated mean daily fiber intake was 5.1 g lower (95% confidence interval (CI), 4.3-5.9 g/day; p < 0.001). Neither dietary potassium intake (p = 0.40) nor dietary fiber intake (p = 0.43) was associated with circulating potassium in a model adjusted for time point, eGFR, treatment with a renin-angiotensin-aldosterone system blocker, serum bicarbonate concentration, and body surface area. CONCLUSIONS: Dietary potassium and fiber intake are closely related but were not associated with circulating potassium levels in pediatric CKD. A higher-resolution version of the graphical abstract is available as Supplementary information.

Does dietary potassium intake associate with hyperkalemia in patients with chronic kidney disease?

BACKGROUND: Dietary potassium restriction is a strategy to control hyperkalemia in chronic kidney disease (CKD). However, hyperkalemia may result from a combination of clinical conditions. This study aimed to investigate whether dietary potassium or the intake of certain food groups associate with serum potassium in the face of other risk factors. METHODS: We performed a cross-sectional analysis including a nondialysis-dependent CKD (NDD-CKD) cohort and a hemodialysis (HD) cohort. Dietary potassium intake was assessed by 3-day food records. Underreporters with energy intake lower than resting energy expenditure were excluded. Hyperkalemia was defined as serum potassium >5.0 mEq/L. RESULTS: The NDD-CKD cohort included 95 patients {median age 67 [interquartile range (IQR) 55-73] years, 32% with diabetes mellitus (DM), median estimated glomerular filtration rate 23 [IQR 18-29] mL/min/1.73 m2} and the HD cohort included 117 patients [median age 39 (IQR 18-67) years, 50% with DM]. In NDD-CKD, patients with hyperkalemia (36.8%) exhibited lower serum bicarbonate and a tendency for higher serum creatinine, a higher proportion of DM and the use of renin-angiotensin-aldosterone system blockers, but lower use of sodium bicarbonate supplements. No association was found between serum and dietary potassium (r = 0.01; P = 0.98) or selected food groups. Conditions associated with hyperkalemia in multivariable analysis were DM {odds ratio [OR] 3.55 [95% confidence interval (CI) 1.07-11.72]} and metabolic acidosis [OR 4.35 (95% CI 1.37-13.78)]. In HD, patients with hyperkalemia (50.5%) exhibited higher serum creatinine and blood urea nitrogen and lower malnutrition inflammation score and a tendency for higher dialysis vintage and body mass index. No association was found between serum and potassium intake (r = -0.06, P = 0.46) or food groups. DM [OR 4.22 (95% CI 1.31-13.6)] and serum creatinine [OR 1.50 (95% CI 1.24-1.81)] were predictors of hyperkalemia in multivariable analyses. CONCLUSIONS: Dietary potassium was not associated with serum potassium or hyperkalemia in either NDD-CKD or HD patients. Before restricting dietary potassium, the patient's intake of potassium should be carefully evaluated and other potential clinical factors related to serum potassium balance should be considered in the management of hyperkalemia in CKD.

Rising Trend of Hypokalemia Prevalence in the US Population and Possible Food Causes.

Background: Potassium intake deficiency is a chronic issue in the US and many other countries. Possible causes of the deficiency are understudied.Objective: This study examined potassium deficiency in the US population and possible causes for the new trend.Methods: Serum potassium data of 28,379 men and 29,617 women between ages 12 and 80 years old who participated in the US National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016 were examined. Blood samples were collected by NHANES and blood biochemistry data were measured in designed laboratories. The data were released bi-annually. Possible causes of low potassium intakes were explored.Results: There was an apparent decline of serum potassium in the US population between ages 12 and 80 years from 1999 to 2016. Annual average serum potassium concentrations changed from 4.14 ± 0.01 to 3.97 ± 0.01 mmol/l during this period. Hypokalemia prevalence in the US rose from 3.78%±0.68% to 11.06%±1.08% during this period with a higher hypokalemia prevalence in non-Hispanic black than in non-Hispanic white persons. It is possible that declining potassium concentration in food sources in the US contributed to lower potassium intake and increasing potassium deficiency.Conclusion: The rising trend of hypokalemia prevalence in the US population between 1999 and 2016 is alarming. Renewed efforts to reduce potassium intake deficiency in the US at population level are needed. The impact of possible decreasing crop available potassium levels and increasing consumption of processed food on the potassium deficit trend in the US are possible explanations for the rise in hypokalemia prevalence and require further study.

How SARS-CoV-2 might affect potassium balance via impairing epithelial sodium channels?

Severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) is the causative agent of current coronavirus disease 2019 (COVID-19) pandemic. Electrolyte disorders particularly potassium abnormalities have been repeatedly reported as common clinical manifestations of COVID-19. Here, we discuss how SARS-CoV-2 may affect potassium balance by impairing the activity of epithelial sodium channels (ENaC). The first hypothesis could justify the incidence of hypokalemia. SARS-CoV-2 cell entry through angiotensin-converting enzyme 2 (ACE2) may enhance the activity of renin-angiotensin-aldosterone system (RAAS) classical axis and further leading to over production of aldosterone. Aldosterone is capable of enhancing the activity of ENaC and resulting in potassium loss from epithelial cells. However, type II transmembrane serine protease (TMPRSS2) is able to inhibit the ENaC, but it is utilized in the case of SARS-CoV-2 cell entry, therefore the ENaC remains activated. The second hypothesis describe the incidence of hyperkalemia based on the key role of furin. Furin is necessary for cleaving both SARS-CoV-2 spike protein and ENaC subunits. While the furin is hijacked by the virus, the decreased activity of ENaC would be expected, which causes retention of potassium ions and hyperkalemia. Given that the occurrence of hypokalemia is higher than hyperkalemia in COVID-19 patients, the first hypothesis may have greater impact on potassium levels. Further investigations are warranted to determine the exact role of ENaC in SARS-CoV-2 pathogenesis.

Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis.

BACKGROUND: Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. METHOD: We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. RESULTS: Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (-0.42 mmol/L; 95% CI: -0.63 to -0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. CONCLUSIONS: SZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

Serum potassium levels and prognosis in HBV-associated decompensated cirrhosis.

BACKGROUND: Serum potassium disorders are commonly seen in patients with advanced cirrhosis and have a detrimental effect on clinical outcome, but its role in HBV-related decompensated cirrhosis (DeCi) is remained to be illustrated. We aim to assess the effects of serum potassium on outcomes in HBV-DeCi patients. METHODS: Retrospective study included 155 subjects. Multivariate analysis was used to determine the independent prognostic factor. Predictive ability of mortality for variables was determined using the receiver operating characteristics curves. RESULTS: The 30-day in-hospital mortality was 12.9%. Serum potassium levels differed markedly between survivors and non-survivors. On multivariate analysis, Model for End-Stage Liver Disease (MELD) score and serum potassium level were identified as independent predictors of outcomes in HBV-DeCi patients. The combination of serum potassium and MELD score could improve prognostic accuracy in these patients. CONCLUSIONS: Our findings suggest that serum potassium is an effective predictor for poor outcomes in HBV-DeCi patients.

Comparison of hemodynamic changes and serum potassium levels in the use of succinylcholine and cisatracurium in electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is nowadays used commonly as one the most effective treatment methods in psychiatric disorders. In patients undergoing ECT, succinylcholine is usually used. In addition, cisatracurium is occasionally used on a case report basis globally. In this study, we compared the hemodynamic changes and serum potassium levels in the use of succinylcholine and cisatracurium in ECT. MATERIALS AND METHODS: The current crossover clinical trial was performed on 45 patients who were candidates for ECT between 2017 and 2018. The patients were given succinylcholine or cisatracurium randomly on two separate occasions of ECT. The independent t-test and Chi square Test were used to compare the data. RESULTS: Comparison of mean systolic blood pressure (P = 0.14), diastolic blood pressure (P = 0.33), and mean arterial pressure (P = 0.23) did not show any significant difference between the two groups. The induced seizure duration (P = 0.002), return of spontaneous respiratory from seizure ending (P = 0.001), and apnea duration (P = 0.01) were significantly higher in the cisatracurium group compared to the succinylcholine group. However, the frequency of tachycardia in cisatracurium group was lower than the succinylcholine group (P < 0.001). In addition, the serum potassium level had a significant difference (P < 0.001) between the two groups. CONCLUSION: Using cisatracurium can be an alternative to succinylcholine during ECT since it causes less elevation in serum potassium and creates a longer duration of induced seizure, more rapid re emergence of spontaneous breathing at the end of seizure (P = 0.001), and a lower prevalence of tachycardia compared to succinylcholine (P < 0.001).

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas.

Clinical characterization of patients with primary aldosteronism plus subclinical Cushing's syndrome.

BACKGROUND: Primary aldosteronism (PA) plus subclinical Cushing's syndrome (SCS), PASCS, has occasionally been reported. We aimed to clinically characterize patients with PASCS who are poorly profiled. METHODS: A population-based, retrospective, single-center, observational study was conducted in 71 patients (age, 58.2 ± 11.2 years; 24 males and 47 females) who developed PA (n = 45), SCS (n = 12), or PASCS (n = 14). The main outcome measures were the proportion of patients with diabetes mellitus (DM), serum potassium concentration, and maximum tumor diameter (MTD) on the computed tomography (CT) scans. RESULTS: The proportion of DM patients was significantly greater in the PASCS group than in the PA group (50.0% vs. 13.9%, p <  0.05), without a significant difference between the PASCS and SCS groups. Serum potassium concentration was significantly lower in the PASCS group than in the SCS group (3.2 ± 0.8 mEq/L vs. 4.0 ± 0.5 mEq/L; p <  0.01), without a significant difference between the PASCS and PA groups. Among the 3 study groups of patients who had a unilateral adrenal tumor, MTD was significantly greater in the PASCS group than in the PA group (2.7 ± 0.1 cm vs. 1.4 ± 0.1 cm; p <  0.001), without a significant difference between the PASCS and SCS groups. CONCLUSIONS: Any reference criteria were not obtained that surely distinguish patients with PASCS from those with PA or SCS. However, clinicians should suspect the presence of concurrent SCS in patients with PA when detecting a relatively large adrenal tumor on the CT scans.

Factors that predict recurrent spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND: The recurrence rate of spontaneous bacterial peritonitis (SBP) is increasing in cirrhotic patients. Antibiotic prophylaxis should be prescribed in all cirrhotic patients after the first episode of SBP. However, antibiotics promote the development of antibiotic-resistant bacteria. OBJECTIVE: To identify the factors that predict the recurrence of SBP after the first episode in cirrhotic patients to optimise the stratification for secondary antibiotic prophylaxis. METHODS: This retrospective study included 145 cirrhotic patients who had their first SBP episode during 2011-2015. The 86 patients who survived were divided into either the SBP recurrence or non-recurrence group according to patient SBP outcome during the 2-year follow-up. Demographical, clinical and laboratory parameters were recorded at SBP diagnosis and before hospital discharge. SBP recurrence rate, recurrence-free survival and in-hospital mortality were also analysed. RESULTS: The recurrence rate of SBP after the first episode was 69.8% (60/86), and the median recurrence-free survival time was 142 days. The in-hospital mortality rate was 40.7% (59/145). The significant predictive factors for recurrence of SBP were serum potassium ≥4 mEq/L (HR: 1.89; P = .028), serum albumin ≤2 g/dL (HR: 2.5; P = .003) at diagnosis of SBP and platelet count before discharge ≤100 000/microliter (HR: 1.93; P = .029). CONCLUSION: SBP frequently recurs in cirrhotic patients. Serum potassium ≥4 mEq/L, serum albumin ≤2g/dL at SBP diagnosis and platelet count ≤100 000/microliter before discharge were identified as factors that may predict the recurrence of SBP after the first episode.

Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium. SETTING & STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts. SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January 2018. ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. RESULTS: The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g). LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays. CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in Incident Peritoneal Dialysis Patients.

BACKGROUND: Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable. METHODS: Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations. RESULTS: Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics. CONCLUSION: Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity.