Plasma Potassium Concentration Research Articles

Plant-based diet in hyperkalemic chronic kidney disease patients receiving sodium zirconium cyclosilicate: a feasibility clinical trial

BackgroundPlant-based diets (PBD) may induce hyperkalemia in chronic kidney disease (CKD) patients. ObjectivesWe explored the safety and feasibility of PBD in hyperkalemic CKD patients receiving the potassium binder sodium zirconium cyclosilicate (SZC). MethodsIn the current 6-wk trial, 26 hyperkalemic patients with CKD stage 4–5 not on dialysis received a low-protein low-potassium diet plus SZC for 3 wk and then a PBD with high potassium content delivered as a weekly food basket while continuing SZC for subsequent 3 wk. Plasma potassium was monitored weekly and SZC was titrated to achieve normokalemia. The 24-h urine excretion of potassium and sodium, 24-h food records, dietary quality, nutritional status, Bristol stool scale, Quality of life (QoL), and renal treatment satisfaction were assessed at baseline (week 0), week 3, and week 6. ResultsMean plasma potassium decreased from 5.5 to 4.4 mEq/L within 48–72 h after baseline, then rose to 4.7–5.0 mEq/L throughout the remaining study period following dose adjustments of SZC that matched the increased potassium intake of PBD from week 3 to week 6. Over the study period, 24-h urinary potassium excretion decreased from week 0 to week 3 and increased from week 3 to week 6. During the study, 58% of patients had fasting plasma potassium between 3.5 and 5.0 mEq/L and there was no episode of plasma potassium >6.5 mEq/L or <3.0 mEq/L during the study. P-carbon dioxide increased from baseline until week 6 (21 ± 2 to 23 ± 2 mEq/L; P = 0.002; mean ± SD), whereas remaining laboratory values remained unchanged. Fiber intake, dietary quality, the domain physical functioning from QoL, and 1 question of renal treatment satisfaction improved, whereas stool type and frequency did not change after starting PBD. ConclusionsPBD in hyperkalemia-prone CKD patients receiving SZC improved dietary quality and increased the intake of healthy foods, whereas plasma potassium concentration remained stable within normal values for most patients. Trial registration numberThis trial was registered at the https://clinicaltrials.gov/study/NCT04207203 as NCT04207203.

Serial paired arterial and jugular venous point-of-care values in dogs undergoing manual basic life support.

To evaluate differences in point-of-care (POC) variables obtained from arterial and jugular venous blood in dogs undergoing manual basic life support (BLS) and report changes over time. Experimental study. Small animal research facility. Twenty-four purpose-bred research dogs. Dogs were anesthetized, and arterial catheters were placed before euthanasia. One minute after cardiopulmonary arrest, BLS consisting of manual chest compressions and ventilation delivered via endotracheal intubation, face mask, mouth-to-nose, or no ventilation was initiated. Paired arterial and jugular venous blood samples were obtained for POC testing before euthanasia (T0), at 3minutes (T3), and at 6minutes (T6) into BLS. The association of POC variables with arterial or venous sample type while controlling for type of ventilation and sampling timepoint was determined using a generalized linear mixed model. Variables obtained from arterial and venous blood samples were compared over time using repeated measures ANOVA or Friedman test. Pao2, anion gap, potassium, chloride, glucose concentration, and PCV were significantly higher in arterial blood samples compared with venous samples (P<0.03). By T6, arterial glucose concentration, arterial and venous base excess, venous pH, and plasma lactate, potassium, creatinine, bicarbonate, and sodium concentrations were significantly increased, and arterial and venous Po2, ionized calcium concentration, PCV, and total plasma protein concentration were significantly decreased from T0 (P<0.05). Although statistically significant, arteriovenous differences and changes in POC blood variables during BLS were small and not clinically relevant over time. Given the challenges of arterial blood sampling, it may be reasonable to pursue venous blood sampling during CPR. Further studies in dogs undergoing BLS and advanced life support are needed to better understand the potential clinical role of POC testing during CPR.

Endocrine data provide further evidence of physiologic derangement in sea turtles affected by the Deepwater Horizon oil spill

This study was conducted to characterize the adrenocortical and thyroid status of Kemp’s ridley sea turtles Lepidochelys kempii that were affected by the Deepwater Horizon oil spill. A plasma aldosterone assay was validated for L. kempii, and it was used along with previously validated assays for corticosterone and free thyroxine to assess hormone concentrations of 30 L. kempii that were hospitalized due to oil exposure, representing 2 severities of oiling (lightly or heavily oiled). Hormone concentrations were also assessed in relation to 8 clinical biochemical analytes. Analysis of paired samples indicated that oiled turtles had significantly higher initial aldosterone and corticosterone concentrations, which declined during convalescence (average 96 and 90% decrease, respectively). Thyroxine concentrations significantly increased between admission and convalescence (average 65% increase). Initial biochemical data indicated significantly higher plasma potassium, ionized magnesium, and lactate concentrations compared to convalescent values. Aldosterone concentrations were positively correlated with corticosterone, negatively correlated with free thyroxine, and variably correlated with several clinical biochemical analytes. Results of this study indicate that L. kempii had robust adrenocortical activity after oiling, capture, and transport to the hospital, regardless of the degree of oiling, resulting in very high plasma concentrations of aldosterone and corticosterone. This study also confirms that aldosterone can be reliably measured in sea turtle plasma samples, providing another diagnostic tool for the physiologic assessment of this Critically Endangered species.

Differential effects of contracting muscle mass and relative exercise intensity on arterial plasma potassium concentration during and following incremental arm and leg cycling exercise

Whilst arm cycling is commonly used during clinical testing and rehabilitation, the associated changes in arterial plasma K+ concentration ([K+]a) and thus possible risks of associated hyperkalaemia and hypokalaemia are unknown. During exercise, K+ is released from contracting skeletal muscles and simultaneously taken up by inactive muscles, with [K+]a increasing markedly during intense exercise. Hence during exercise [K+]a should be influenced by both the contracting muscle mass and the relative exercise intensity. We therefore investigated the effects of incremental one-arm (1ARM) and two-leg (2LEGS) cycling on [K+]a, and on lactate ([Lac-]), hydrogen ([H+]), adrenaline and noradrenaline. Eight healthy participants performed 1ARM, rested (3.0 ± 0.2 h, mean±SE) then performed 2LEGS, with radial arterial blood sampled at rest, during common submaximal workrates (25, 50 W), peak workrate and 1–30 min post-exercise. During exercise at 50 W, VO2, [K+]a and [Lac-]a were higher during 1ARM than 2LEGS (P < 0.05). In contrast, at peak exercise, 2LEGS (272 ± 15 W) elicited higher VO2, [K+]a, [Lac-]a, [adrenaline]a and [noradrenaline]a than 1ARM (57 ± 4 W) (P < 0.05), with [H+]a elevated only in 2LEGS (P < 0.05). A curvilinear response for [K+]a versus %VO2peak was similar between modes, until diverging close to VO2peak. The slope of the log[K+]a versus %VO2peak regression was higher in 2LEGS (P < 0.01), indicating greater [K+]a throughout exercise utilising a larger muscle mass, and similarly for [Lac-]a. In conclusion, during exercise utilising a smaller contracting muscle mass, [K+]a and [Lac-]a were greater at the same absolute submaximal work rate compared to utilising a large muscle mass. Whilst responses were similar between modes when expressed against relative exercise intensity, [K+]a and [Lac-]a were higher during exercise with a large muscle mass. Hence, for submaximal exercise, the relative intensity is more important in determining [K+]a and [Lac-]a, but the size of the contracting muscle mass still exerts a positive effect, whilst during peak exercise, the size of the active muscle mass was more important in determining [K+]a and [Lac-]a. Furthermore, arm cycling did not induce marked disturbances in [K+]a during or after exercise, suggesting minimal associated myocardial risks and thus supporting its safe use in clinical and aged populations.

Unexpected Hyperkalemia During Kawasaki Disease

Pseudohyperkalemia is defined as a markedly elevated serum potassium level with a normal plasma potassium concentration. It is mainly caused by leucocytosis and thrombocytosis. Here we report an infant treated with aspirin for Kawasaki disease who developed hyperkalemia during follow-up. He was finally diagnosed with pseudohyperkalemia based on a normal whole blood potassium level measured with a blood gas analyser.

Inferring personal intake recommendations of phosphorous and potassium for end-stage renal failure patients by simulating with Bayesian hierarchical multivariate model.

Most end-stage renal disease (ESRD) patients face a risk of malnutrition, partly due to dietary restrictions on phosphorous and, in some cases, potassium intake. These restrictions aim to regulate plasma phosphate and potassium concentrations and prevent the adverse effects of hyperphosphatemia or hyperkalemia. However, individual responses to nutrition are known to vary, highlighting the need for personalized recommendations rather than relying solely on general guidelines. In this study, our objective was to develop a Bayesian hierarchical multivariate model that estimates the individual effects of nutrients on plasma concentrations and to present a recommendation algorithm that utilizes this model to infer personalized dietary intakes capable of achieving normal ranges for all considered concentrations. Considering the limited research on the reactions of ESRD patients, we collected dietary intake data and corresponding laboratory analyses from a cohort of 37 patients. The collected data were used to estimate the common hierarchical model, from which personalized models of the patients' diets and individual reactions were extracted. The application of our recommendation algorithm revealed substantial variations in phosphorus and potassium intakes recommended for each patient. These personalized recommendations deviate from the general guidelines, suggesting that a notably richer diet may be proposed for certain patients to mitigate the risk of malnutrition. Furthermore, all the participants underwent either hospital, home, or peritoneal dialysis treatments. We explored the impact of treatment type on nutritional reactions by incorporating it as a nested level in the hierarchical model. Remarkably, this incorporation improved the fit of the nutritional effect model by a notable reduction in the normalized root mean square error (NRMSE) from 0.078 to 0.003. These findings highlight the potential for personalized dietary modifications to optimize nutritional status, enhance patient outcomes, and mitigate the risk of malnutrition in the ESRD population.

Investigation of Potassium Chloride for Euthanasia of Anesthetized African Clawed Frogs (Xenopus laevis).

Euthanasia is frequently performed in amphibians, but techniques are currently limited in number and variable in effectiveness. The current study examined the use of potassium chloride (KCl) for euthanasia of anesthetized African clawed frogs (Xenopus laevis). Twenty adult, female African clawed frogs were anesthetized by immersion in buffered tricaine methanesulfonate (MS-222) for 5 min beyond loss of righting reflex. Frogs were then randomly assigned to receive one of 4 treatments: KCl via intracardiac injection (10 mEq/kg; IC, n = 5), intracoelomic injection (100 mEq/kg; ICe, n = 5), immersion (4,500 mEq/L; IMS, n = 5), or no treatment (C, n = 5). After treatment, serial heart rate was measured via Doppler device until either the loss of Doppler sounds, a 60-min endpoint (IC, ICe, IMS), or recovery (C). Times to loss of righting reflex, loss of Doppler sounds, and/or recovery were recorded. Plasma potassium concentrations were measured immediately after Doppler sound cessation in frogs in IC (n = 1), ICe (n = 2), and IMS (n = 5). Injection failure occurred in 1 IC frog, and 1 Ice frog regained spontaneous movement 4 min after treatment administration. Data from these 2 frogs were not included in statistical analysis. Doppler sound cessation occurred in 4 of 4, 4 of 4, 0 of 5, and 0 of 5 frogs in IC, ICe, IMS, and C, respectively. Median (range) times to Doppler sound cessation in IC and ICe were 6 (0 to 16) s and 18 (10 to 25) min, respectively. Plasma potassium concentration was greater than 9.0 mmol/L in sampled frogs. Intracardiac KCl at 10 mEq/kg and intracoelomic KCl at 100 mEq/kg were effective for euthanasia of anesthetized African clawed frogs. Return to MS-222 solution after KCl administration may be warranted to prevent unintended, premature anesthetic recovery prior to death.

Alterations in Oxidative Stress Markers and Na,K-ATPase Enzyme Properties in Kidney after Fructose Intake and Quercetin Intervention in Rats.

The study aimed to characterize the consequences of a 15-week intake of 10% fructose on the kidney, with the focus on oxidative stress markers and properties of the Na,K-ATPase enzyme. Various antioxidants naturally occurring in common food were demonstrated to be protective against fructose-induced deterioration of kidneys. Therefore, we also aimed to observe the effect of 6-week quercetin administration (20 mg/kg/day) that was initiated following the 9-week period of higher fructose intake, by determining the concentration of sodium, potassium, creatinine, urea, and glucose in blood plasma and oxidative status directly in the renal tissue. Kinetic studies of renal Na,K-ATPase were utilized for a deeper insight into the molecular principles of expected changes in this enzyme activity under conditions of presumed fructose-induced renal injury. Fructose intake led to increase in body weight gain, plasma glucose and sodium levels, and deterioration of kidney properties, although some compensatory mechanisms were observable. Quercetin administration improved glycemic control in rats exposed to fructose overload. However, an increase in plasma creatinine, a decrease in GSH/GSSG ratio in renal tissue homogenate, and a controversial effect on renal Na,K-ATPase enzyme suggest that quercetin treatment may not be beneficial in the condition of pre-existing renal pathology.

Evaluation of oral telmisartan administration as a suppression test for diagnosis of primary hyperaldosteronism in cats.

Development of a telmisartan-based suppression test may facilitate the diagnosis of primary hyperaldosteronism (PHA) in cats, which remains difficult today. To develop a telmisartan suppression test (TST) that is safe, and able to suppress aldosterone secretion in healthy cats but not in cats with PHA. Ten healthy cats and 6 cats with PHA. Prospective study using a placebo-controlled crossover design to investigate a TST in healthy cats, and evaluation of TST in cats with PHA. Plasma aldosterone concentration, potassium concentration, and systolic blood pressure (SBP) were measured before (T0), and 1 hour (T1) and 1.5 hours after (T1.5) PO administration of 1 mg/kg of telmisartan, 2 mg/kg of telmisartan or placebo. Median age in healthy cats was 3 years old (range, 1-7). In healthy cats, a telmisartan dose of 2 mg/kg significantly decreased aldosterone concentration at T1 and T1.5 compared with T0. Placebo had no significant effect on aldosterone concentration. In cats diagnosed with PHA, a 2-mg/kg dose of telmisartan did not induce any significant change in aldosterone concentration at T1 or T1.5 compared with T0. No adverse effects of telmisartan (e.g., hyperkalemia, systemic hypotension) were observed in any cats. The oral TST shows promise as a diagnostic test for the diagnosis of PHA in cats.

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium.

Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms. Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage. A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .

Ultrastructure of Adrenal Glands in Sodium-deficient Pregnant Rats

The ultrastructure of the zona glomerulosa of the rat adrenal was studied in nonpregnant and pregnant animals receiving either adequate or restricted sodium intakes. Data on weight gain and food intake, hematocrit value and plasma sodium and potassium concentrations, histological observations, and the reproductive performance of pregnant animals were used in interpreting ultrastructural findings. Striking ultrastructural characteristics distinguished cells from the sodium-restricted pregnant animals from those of the other ex perimental groups. In particular, there were numerous lysosomes, autophagic vacuoles and cytoplasmic vacuoles devoid of cellular material. These pathologi cal cellular changes should be considered in evaluating the practice of prescrib ing sodium-restricted diets during normal human pregnancy. J. Nutr. 101: 1045-1056, 1971.

S-54-2: ROLE OF THE THIAZIDE-SENSITIVE NA+:CL- COTRANSPORTER IN THE BLOOD PRESSURE-LOWERING EFFECT OF POTASSIUM RICH DIETS.

Evidence supports that a negative correlation exists between dietary potassium consumption and blood pressure levels in the population. It has also been well documented that increasing dietary potassium consumption, increases urinary sodium excretion. The molecular mechanisms that contribute to this latter phenomenon are under investigation. Recent evidence suggests that the thiazide-sensitive Na+:Cl- cotransporter, NCC, may play a key role in this regard. For instance, in mouse models, variations in blood pressure and natriuresis observed in response to altered potassium intake are significantly blunted in NCC deficient mice. NCC activity indirectly modulates urinary potassium excretion and NCC activity is tightly regulated in response to subtle alterations in plasma potassium concentration that occur in response to dietary potassium consumption changes. The molecular mechanisms that mediate this modulation are complex and their characterization has significantly advanced in recent years. Such mechanisms will be discussed in the presentation. The most recent advances will be highlighted.

Management of hyperkalemia in critically ill renal patients undergoing peritoneal dialysis

Hyperkalemia is defined as a plasma or serum potassium concentration above the established reference range and is frequently encountered in various pathologies. The potassium gradient between the intra- and extracellular compartments plays a key role in action potential generation by excitable cells. Serum potassium concentration in patients diagnosed with chronic kidney disease is usually balanced, but hyperkalemia may develop in patients with acute kidney injury in stage III and IV. According to recent studies, hyperkalemia is a serious complication in patients diagnosed with chronic kidney disease in IRIS stage II, III and IV. The occurrence and severity of hyperkalemia may also be aggravated by the inadequate administration of potassium in enteral or parenteral fluids, metabolic acidosis, and the use of angiotensin-converting enzyme inhibitors. Excess potassium is continuously excreted by the kidneys, and its concentrations in urine are higher than those in serum. Compromised excretion will predictably lead to both hyperkalemia and azotemia. The extent of these changes is variable and depends on the underlying etiology. Hyperkalemia can be treated by antagonizing its effects on cell membranes with calcium gluconate, or by introducing extracellular potassium into cells with sodium bicarbonate or glucose. Also, the removal of potassium from the body can be done through dialysis.

Treatment strategies for hyperkalemia secondary to urethral obstruction in 50 male cats: 2002-2017.

The aims of this study were: to describe the potassium-lowering treatment strategies used to manage moderate-to-severe hyperkalemia in male cats with urethral obstruction (UO); to determine how much dextrose was required per unit of insulin to prevent hypoglycemia; to determine whether early initiation of a dextrose continuous rate infusion (CRI) prevented hypoglycemia; and to determine whether in-hospital mortality was associated with presenting plasma potassium concentration ([K+]). The medical records of male cats presenting with a [K+] ⩾7.0 mEq/l due to UO that had another [K+] measured within 6 h were reviewed retrospectively. All [K+] values within the first 6 h, blood glucose concentrations, treatments for hyperkalemia and survival to discharge were recorded. Analyses were performed to test for associations between dextrose:insulin ratios or method of dextrose administration and the development of hypoglycemia; and for presenting [K+] and mortality. Normally distributed groups of continuous data were compared with a t-test and categorical data were compared with a Fisher's exact test. Fifty cats were included. Mean presenting [K+] was 8.9 ± 1.0 mEq/l, while the mean final [K+] within 6 h was 6.6 ± 1.4 mEq/l. Forty-two (84%) cats were treated with intravenous fluids and 40 (80%) were treated with dextrose and insulin. Median dextrose:insulin ratio was 2 g/u (range 0.4-100). No dextrose:insulin ratio was found to protect against hypoglycemia, and 3/8 cats that became hypoglycemic had received ⩾2 g dextrose per unit of insulin. There was no association between the early initiation of a dextrose-containing CRI and avoidance of hypoglycemia. No association was found between presenting [K+] and mortality. While no specific dextrose:insulin ratio was found to protect against hypoglycemia, there is evidence that the commonly recommended dextrose:insulin ratio of 2 g/u may be inadequate in preventing hypoglycemia in every cat. Severity of hyperkalemia was not associated with mortality.

Pathophysiological Electrolyte Changes Connoted via Antagonism of Serotonin Receptor in Experimental Animals

Background: Atypical antipsychotics are a subclass of antipsychotics that have emerged primarily since the 1970s for the treatment of psychiatric disorders. They are sometimes referred to as second-generation antipsychotics (SGAs). Several atypical antipsychotics have received regulatory approval for the treatment of disorders such as bipolar disorder, schizophrenia, irritability in autism, and as adjunctive treatment for major depressive disorders. Objectives: The purpose of the following study was to evaluate the effect of two widely known atypical antipsychotics, aripiprazole, and risperidone, on pathophysiological fluctuations in electrolytes. Several other studies were based on the following ideas, which brought a variety of different perspectives. As can be seen in the following evaluation, although atypical antipsychotics reduce the chance of extrapyramidal symptoms, it leads to impairment of renal function and destruction of renal histo-morphology. Materials and Methods: Thirty rats (10 per group) were used for this study, control group received normal saline, aripiprazole group received 10mg/kg//day, and risperidone group received 20mg/kg//day. The duration of therapy was long up to 3 months. Results: the results confirmed that both drugs reduced plasma sodium and chloride concentration with no effects on plasma potassium and calcium concentration. Moreover, the histomorphology at microscopic level shown no defects after 3 months of therapy. Conclusion: the outcome confirmed no deleterious defects associated with aripiprazole and risperidone when used for 3 months.

Utilization of mechanistic modelling and simulation to analyse fenspiride proarrhythmic potency - Role of physiological and other non-drug related parameters.

Fenspiride, a drug that had been used for decades for the treatment of respiratory diseases, was recently withdrawn from the market due to the potential risk of QT prolongation and proarrhythmia. This is the first such withdrawal for many years and hence poses a question whether such risk could have been predicted and to what degree non-drug-specific parameters play a role in the reported QT prolongation and cases of TdP. The study aim was to test various 'what-if' scenarios to assess the influence of age, gender, heart rate, and plasma potassium concentration on QT interval prolongation due to various doses of fenspiride with the use of mechanistic mathematical modelling. Concentration-time profiles were simulated with the use of a PBPK model developed based on published physico-chemical data, data from in vitro ADME experiments, and in vivo PK study results. Pharmacodynamic effect, that is, drug-triggered pseudoECG signal modification was simulated using a biophysically detailed model of human cardiac myocytes. Analysis of the qNet metric was also performed to classify proarrhythmic risk related to fenspiride. In the simulation study, arrhythmia was not observed even in the 'what-if' scenarios with extreme exposure, age, heart rate, and plasma potassium concentration. The qNet metric value positioned fenspiride in the intermediate risk class. It can be hypothesized that the clinically observed arrhythmia cases were not directly caused by fenspiride alone but a combination of multiple factors, including comedications.

Pharmacokinetic and pharmacodynamic properties of orally administered torasemide in healthy cats.

BackgroundIn people and dogs, torasemide has higher bioavailability, longer half‐life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited.ObjectiveTo assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin‐angiotensin‐aldosterone system (RAAS).AnimalsSix clinically healthy adult European shorthair cats.MethodsRandomized 4‐period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model.ResultsMean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half‐life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose‐dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration.Conclusions and Clinical ImportanceA single torasemide dose leads to a significant increase in diuresis and renin‐angiotensin‐aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.

Recurrent Hypokalemia and Adrenal Steroids in Patients With APECED.

ContextHypokalemia is a common finding in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) but its exact cause often remains unknown.ObjectiveTo explore the prevalence and etiology of hypokalemia and the role of adrenal steroids therein in a cohort of patients with APECED.MethodsWe performed a cross-sectional assessment and retrospective data collection on 44 Finnish patients with APECED to identify subjects with episodes of hypokalemia. Also 68 healthy matched controls attended the cross-sectional evaluation. Factors associating with a tendency for hypokalemia were analyzed by reviewing medical records during 1960-2021 and performing a cross-sectional analysis of serum adrenal steroids.ResultsIn total 14 of the 44 APECED patients (32%) had episodes of hypokalemia; 2 presented with hypokalemia at cross-sectional evaluation and 12 had a history of hypokalemia before the cross-sectional evaluation. Hypokalemic episodes started at the median age of 14.1 years; 12/14 (86%) had primary adrenal insufficiency (PAI). The median number of hypokalemic periods per year was 0.3 (range 0.04-2.2); the frequency correlated positively with the number of clinical APECED manifestations at the time of cross-sectional evaluation (r=0.811, p<0.001). Etiologies of hypokalemia varied but episodes often occurred when new clinical manifestations developed and during hospitalizations. Three patients had kidney defects, also associated with electrolyte imbalances. Severity of hypokalemia varied (range 2.2-3.2 mmol/L), but no severe complications were observed. At cross-sectional evaluation, patients with PAI (n = 30) had significantly lower median plasma potassium and higher sodium concentration than controls, suggesting that fludrocortisone treatment contributed to hypokalemia. Detailed analysis of adrenal steroids provided no conclusive differences between patients with and without episodes of hypokalemia.ConclusionsIn APECED, hypokalemia is common and varies in terms of frequency, etiology, and severity. PAI and kidney disease predispose to hypokalemia. In addition, hypokalemic periods seem to be more common in patients with more severe phenotype of APECED.

Effect of potassium supplementation on osmoregulatory and stress response of Pangasianodon hypophthalmus (Sauvage, 1878) with Spinacia oleracea L. in aquaponics.

This study evaluated the effect of different potassium supplementation dosages on the physiological responses of Pangasianodon hypophthalmus reared in an aquaponic system with Spinacia oleracea L. for 60 days. The system comprised of a rectangular fish tank of 168 l capacity (water volume=100 l) with nutrient film technique (NFT)-based hydroponic component with fish to plant ratio of 2.8kg m-3 : 28 plants m-2 in all the treatments. The osmoregulatory and stress parameters of P. hypophthalmus at four different potassium dosages of T1 (90 mg l-1 ), T2 (120 mg l-1 ), T3 (150 mg l-1 ) and T4 (180 mg l-1 ) were compared with C (control, 0mg l-1 ) to examine the potassium level to be applied to aquaponics. The water quality parameters and fish production were found to have no adverse impact due to potassium supplementation. The spinach yield during two harvests, i.e., before and after potassium supplementation, revealed that the yield was significantly higher (P < 0.05) after supplementation with the highest yield in T3 and T4. The osmoregulatory parameters such as plasma osmolality, Na+ , K+ ATPase activity in gill and plasma ionic profile (Cl- , Ca2+ and Na+ ) showed an insignificant variation (P > 0.05) between control and treatments except for higher plasma potassium concentration (1.98 ± 0.19 mmol l-1 ) in T4. The stress and antioxidant enzyme analysis exhibited significantly higher plasma glucose and superoxide dismutase (SOD) activity in gill and liver in T4, whereas cortisol and catalase showed an insignificant difference (P > 0.05). The experimental findings demonstrated that the potassium dosage up to 150 mg l-1 could be suggested as optimum for P. hypophthalmus and spinach aquaponics without impairing the health and oxidative status of P. hypophthalmus.