Effects of Preoperative Oral Carbohydrate Electrolyte Drinks on Preoperative Hypokalemia Incidence in Patients Scheduled for Laparoscopic Colorectal Resection: A Three-Arm Randomized Clinical Trial.

PURPOSE: In our previous study, hypokalemia incidence was high in patients scheduled for laparoscopic colorectal resection. This trial was conducted to verify the effects of preoperative carbohydrate drinks containing potassium in these patients. DESIGN: A three-arm randomized controlled design was used. METHODS: Patients were randomly assigned to control, placebo, and treatment groups. In the control group, patients fasted from midnight. In the placebo group, patients fasted from midnight and received carbohydrate drinks 2 to 3 hours before surgery. In the treatment group, patients fasted from midnight and received carbohydrate drinks containing potassium supplementation 2 to 3 hours before surgery. The primary outcome was the incidence and severity of preoperative hypokalemia. Other outcomes included postoperative gastrointestinal function, including the time to postoperative first flatus (FFL) and first feces (FFE), and other complications. FINDINGS: The final analysis included 122 participants. The incidence of preoperative hypokalemia in the treatment group was significantly lower than that in the control and placebo groups (50% vs 88.1% vs 77.5%, P < .001). The severity of hypokalemia in the control and placebo groups was greater than that in the treatment group. No regurgitation or aspiration occurred in the three groups. No significant differences were observed among the three groups regarding time to FFL and FFE. CONCLUSIONS: Preoperative carbohydrate drinks containing potassium significantly reduced the incidence of preoperative hypokalemia and improved preoperative thirst and hunger, but did not reduce the postoperative time to FFL and FFE or length of hospital stay. However, as part of the enhanced recovery after surgery protocol, preoperative carbohydrate drinks containing potassium should be considered, as early as first admittance to hospital.

Higher Parenteral Electrolyte Intakes in Preterm Infants During First Week of Life: Effects on Electrolyte Imbalances.

OBJECTIVES: This study aimed to investigate the effects of a higher intake of electrolytes from parenteral nutrition (PN) on plasma electrolyte concentrations in very low birth weight (VLBW, <1500 g) infants. METHODS: This was a single-center cohort study including all VLBW infants born before (n = 81) and after (n = 53) the implementation of a concentrated PN regimen. Daily nutritional intakes and plasma concentrations of sodium, chloride, potassium, phosphate, and calcium were collected from clinical charts. RESULTS: During the first postnatal week, electrolyte intakes were higher in infants who received concentrated PN compared with infants who received original PN. Infants who received concentrated PN had a lower incidence of hypokalemia (<3.5 mmol/L; 30% vs 76%, P < 0.001) and severe hypophosphatemia (<1.0 mmol/L; 2.2% vs 17%, P = 0.02). While the relatively high prevalence of severe hypophosphatemia in infants who received original PN can be explained by a phosphorus intake below the recommendation, the potassium intake during the first 3 postnatal days (mean ± SD: 0.7 ± 0.2 mmol/kg/d) was within the recommendation. The prevalence of early hypernatremia was not affected by the different sodium intake in the 2 groups. CONCLUSIONS: In VLBW infants, a sodium-containing PN solution (about 2.7 mmol/100 mL) does not cause hypernatremia during the first days of life. Furthermore, providing at least 1 mmol potassium/kg/d during the first 3 postnatal days might be necessary to prevent early hypokalemia.

Prevention of hypokalaemia and hypomagnesaemia following peripheral stem cell collection - a prospective cohort study.

BACKGROUND AND OBJECTIVES: Citrate-based anticoagulation reduces plasma potassium and free magnesium in patients undergoing peripheral stem cell collections. Whether the effects may be mitigated by pre-procedure oral electrolyte supplements has not been previously assessed. MATERIALS AND METHODS: Results from a historic cohort (2010-2013) guided a systematic prospective intervention in subjects deemed at risk for clinically meaningful hypokalaemia and hypomagnesaemia. From 2015 to 2019, 136 patients were enrolled in the study. Pre- and post-apheresis electrolyte levels were measured, and oral potassium and magnesium supplements were systematically administered based on the pre- electrolyte levels. RESULTS: We saw a 37% absolute reduction in severe hypokalaemia and 39% absolute reduction in hypomagnesaemia in the prospective intervention cohort when compared to the historic cohort. Multivariate analyses indicated that part of the effect was due to the electrolyte intervention, while part of the effect likely stemmed from other procedure-related changes implemented during the study period. CONCLUSION: Oral potassium and magnesium prophylaxis appear to reduce hypokalaemia and hypomagnesaemia following peripheral stem cell collection. Whether the effect size is sufficient to motivate the intervention warrants further investigation, preferably in a prospective randomized trial setting.

Impact of electrolyte-rich dialysate during continuous renal replacement therapy on serum phosphate and potassium in ICU patients.

BACKGROUND: Hypophosphatemia and hypokalemia occur frequently during continuous renal replacement therapy (CRRT). We evaluated serum phosphate and potassium levels in patients administered three different types of dialysis solution. METHODS: The study population consisted of 324 intensive care unit patients who underwent CRRT between January 2015 and December 2018. Patients were divided into three groups: group 1 (n = 105) received Hemosol B0 (no potassium or phosphate); group 2 (n = 78) received Hemosol B0 and potassium-containing solution (MultiBic); and group 3 (n = 141) received phosphate- and potassium-containing solution (Phoxilium), Hemosol B2, Prismasol 2, and Prismasol 4. A different protocol was followed in each group. RESULTS: The incidence rate of hypophosphatemia was 55% lower in group 3 compared to group 1 (incidence rate ratio (IRR) 0.45, 95% confidence interval (CI): 0.33 to 0.61) and 61% lower compared to group 2 (IRR 0.39, 95% CI: 0.29 to 0.53). Group 3 also had a 50% lower incidence rate of hypokalemia compared to group 1 (IRR 0.50, 95% CI: 0.29 to 0.88). The negative slope in phosphate level in group 3 was greater than that in group 1 (ß = 0.19, 95% CI: 0.02 to 0.37, p = 0.032), while the negative slope in the potassium level was greater in group 2 than in group 1(ß = 0.10, 95% CI: 0.03 to 0.17, p = 0.008). Additional intravenous calcium was not used in any case, and most cases of acid-base disturbances were well controlled. CONCLUSIONS: The use of phosphate- and potassium-containing with a proper CRRT protocol prevented decreases in serum phosphate and potassium levels, thus also preventing hypophosphatemia and hypokalemia, and additional replacement during CRRT.

Electrolyte disorders are ERAS-associated in patients undergoing hepato-pancreato-biliary surgery.

PURPOSE: Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. METHODS: Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. RESULTS: The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76 mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41 mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. CONCLUSIONS: ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.

[Incidence and Risk Factors of Hypokalemia in Tazobactam/Piperacillin-administered Patients].

Tazobactam/piperacillin (TAZ/PIPC) is a useful antimicrobial agent with broad antibacterial activity. Hypokalemia is considered a rare side effect of TAZ/PIPC; however, it may occur more often than previously thought. In this study, hypokalemia frequency and risk factors were examined in 420 patients treated with TAZ/PIPC. Our results demonstrated that the hypokalemia incidence was 24.8% (grade 1-2: 18.3%, grade 3-4: 6.4%). In addition, multivariate analysis revealed that age [odds ratio 1.057, 95% confidence interval 1.024-1.090, cutoff value 80.5 years] is a risk factor. Although the "Daily dosage/creatinine clearance" was not significant in multivariate analysis, univariate analysis indicated it be to be significant, with a cutoff value of 294.9 mg/mL/min. Furthermore, a "body mass index of 19.7 kg/m2 or higher", "serum potassium level before administration of 3.95 mEq/L or more", and "no empirical treatment for administration purposes" appeared to prevent the hypokalemia development. Overall, the hypokalemia incidence rate in TAZ/PIPC-administered patients was as high as 20%, with patients aged >80.5 years considered a high-risk group. Thus, careful monitoring of potassium levels in patients treated with TAZ/PIPC, particularly those aged >81 years, is warranted.

TRPV4 deletion protects against hypokalemia during systemic K+ deficiency.

Tight regulation of K+ balance is fundamental for normal physiology. Reduced dietary K+ intake, which is common in Western diets, often leads to hypokalemia and associated cardiovascular- and kidney-related pathologies. The distal nephron, and, specifically, the collecting duct (CD), is the major site of controlled K+ reabsorption via H+-K+-ATPase in the state of dietary K+ deficiency. We (Mamenko MV, Boukelmoune N, Tomilin VN, Zaika OL, Jensen VB, O'Neil RG, Pochynyuk OM. Kidney Int 91: 1398-1409, 2017) have previously demonstrated that the transient receptor potential vanilloid type 4 (TRPV4) Ca2+ channel, abundantly expressed in the CD, contributes to renal K+ handling by promoting flow-induced K+ secretion. Here, we investigated a potential role of TRPV4 in controlling H+-K+-ATPase-dependent K+ reabsorption in the CD. Treatment with a K+-deficient diet (<0.01% K+) for 7 days reduced serum K+ levels in wild-type (WT) mice from 4.3 ± 0.2 to 3.3 ± 0.2 mM but not in TRPV4-/- mice (4.3 ± 0.1 and 4.2 ± 0.3 mM, respectively). Furthermore, we detected a significant reduction in 24-h urinary K+ levels in TRPV4-/- compared with WT mice upon switching to K+-deficient diet. TRPV4-/- animals also had significantly more acidic urine on a low-K+ diet, but not on a regular (0.9% K+) or high-K+ (5% K+) diet, which is consistent with increased H+-K+-ATPase activity. Moreover, we detected a greatly accelerated H+-K+-ATPase-dependent intracellular pH extrusion in freshly isolated CDs from TRPV4-/- compared with WT mice fed a K+-deficient diet. Overall, our results demonstrate a novel kaliuretic role of TRPV4 by inhibiting H+-K+-ATPase-dependent K+ reabsorption in the CD. We propose that TRPV4 inhibition could be a novel strategy to manage certain hypokalemic states in clinical settings.

Development and validation of a dynamic inpatient risk prediction model for clinically significant hypokalemia using electronic health record data.

Purpose: The purpose of this study was to develop a dynamic risk prediction model for inpatient hypokalemia and evaluate its predictive performance. Methods: A retrospective cohort included all admissions aged 18 years and above from 2 large tertiary hospitals in Florida over a 22-month period. Hypokalemia was defined as a potassium value of less than 3 mmol/L, and subsequent initiation of potassium supplements. Twenty-five risk factors (RF) identified from literature were operationalized using discrete electronic health record (EHR) data elements. For each of the first 5 hospital days, we modeled the probability of developing hypokalemia at the subsequent hospital day using logistic regression. Predictive performance of our model was validated with 100 bootstrap datasets and evaluated by the C statistic and Hosmer-Lemeshow goodness-of-fit test. Results: A total of 4511 hypokalemia events occurred over 263 436 hospital days (1.71%). Validated C statistics of the prediction model ranged from 0.83 (Day 1 model) to 0.86 (Day 3), while p-values for the Hosmer-Lemeshow test spanned from 0.005 (Day 1) to 0.27 (Day 4 and 5). For the Day 3 prediction, 9.9% of patients with risk scores in the 90th percentile developed hypokalemia and accounted for 60.4% of all hypokalemia events. After controlling for baseline potassium values, strong predictors included diabetic ketoacidosis, increased mineralocorticoid activity, polyuria, use of kaliuretics, use of potassium supplements and watery stool. Conclusion: This is the first risk prediction model for hypokalemia. Our model achieved excellent discrimination and adequate calibration ability. Once externally validated, this risk assessment tool could use real-time EHR information to identify individuals at the highest risk for hypokalemia and support proactive interventions by pharmacists.

Evaluation and Management of Dehydration in Children.

The article discusses the evaluation of dehydration in children and reviews the literature on physical findings of dehydration. Pediatric dehydration is a common problem in emergency departments and wide practice variation in treatment exists. Dehydration can be treated with oral, nasogastric, subcutaneous, or intravenous fluids. Although oral rehydration is underutilized in the United States, most children with dehydration can be successfully rehydrated via the oral route. Selection of oral rehydration solution and techniques for successful oral rehydration are presented. Appropriate selection and rate of administration of intravenous fluids are also discussed for isonatremic, hyponatremic, and hypernatremic dehydration.

Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study.

PURPOSE: Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB-induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients. METHODS: Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24). FINDINGS: Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB-induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB-induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019-0.47]). IMPLICATIONS: This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.

Occurrence and improvement of renal dysfunction and serum potassium abnormality during administration of liposomal amphotericin B in patients with hematological disorders: A retrospective analysis.

Liposomal amphotericin B (L-AMB) has the potential to cause two major adverse events, renal dysfunction and serum potassium abnormality; however, appropriate clinical management of these events remains unclear. We retrospectively analyzed data regarding 128 hematology patients who received L-AMB in our institute and examined the association between clinical characteristics and renal dysfunction or serum potassium abnormality. We found that the median weight-normalized dose of L-AMB was 2.69mg/kg and the median administration period was 16days. The overall occurrence rates of renal dysfunction and hypokalemia were 55.7% and 76.6%, respectively. Multivariate analysis revealed that pre-existing renal dysfunction (P=0.017) and concomitant use of nephrotoxic (P<0.0001) or antifungal drugs (P=0.012) were independent risk factors for renal dysfunction. A higher infusion volume did not mitigate the risk of renal dysfunction. Hypokalemia occurred significantly less often in men (P=0.028) and in patients who concomitantly used nephrotoxic drugs (P=0.013). Approximately 40% of the adverse events were improved at 30days after L-AMB termination and there was no significant association between these adverse events improvement and L-AMB dosage or infusion volume. Of note, hyperkalemia was observed in more patients who received allogeneic hematopoietic stem cell transplantation (P=0.0303) and concomitant treatment with nephrotoxic drugs (P=0.0281). These results suggest that imprudent reduction of L-AMB dose or redundant intravenous infusion may have minimal benefit for critical patients with suspected invasive fungal infection.

Association between hypo- and hyperkalemia and outcome in acute heart failure patients: the role of medications.

BACKGROUND: The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown. METHODS: Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes. RESULTS: Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function. CONCLUSIONS: In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients.

PURPOSE: To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. MATERIALS AND METHODS: A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. RESULTS: Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia (>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. CONCLUSIONS: High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation.

Outcomes analysis of surgical and medical treatments for patients with primary aldosteronism.

Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using mineralocorticoid receptor antagonists (MRAs). However, the outcomes of surgical and medical treatment for primary aldosteronism (PA) remain unclear. Therefore, we compared the outcomes of surgical and medical treatment for PA and aimed to identify a specific subgroup that might benefit from medical treatment. We identified 269 patients who were treated for PA (unilateral excess: 221 cases; bilateral excess: 48 cases) during 2000-2015 at the Seoul National University Hospital and two other tertiary centers. The main outcomes were the amelioration of hypertension and hypokalemia. Treatment improved hypertension in the surgical treatment group (78.2%) and the medical treatment group (55.6%) (p = 0.001). At the last follow-up, hypokalemia was normalized in the surgical treatment group (97.1%) and the medical treatment group (93.7%, p = 0.046). Among patients with unilateral aldosterone excess, surgery provided advantages in resolving hypertension without worsening renal function. Among patients who were >60 years old or had impaired renal function, surgical and medical treatment provided similar amelioration of hypokalemia and hypertension. Three patients developed hyperkalemia after surgery, and no patients developed hyperkalemia after initiating medical treatment. The surgical treatment group exhibited a lower postoperative estimated glomerular filtration rate (eGFR) and higher serum potassium levels, compared to the medical treatment group. Surgical treatment provided better hypertension and hypokalemia outcomes among patients with PA, compared to medical treatment. However, MRAs may be appropriate for elderly patients with impaired renal function.

Severe hypercalcaemia and hypophosphataemia with an optimised preterm parenteral nutrition formulation in two epochs of differing phosphate supplementation.

OBJECTIVE: To compare in two epochs of differing phosphate provision serum calcium, phosphate, potassium, and sodium concentrations and the frequency of abnormality of these electrolytes and of sepsis in preterm infants who received an optimised higher amino acid-content formulation. DESIGN AND SETTING: Retrospective cohort study at a single tertiary-level neonatal unit. PATIENTS: Preterm infants given parenteral nutrition (PN) in the first postnatal week during two discrete 6-month epochs in 2013-2014. INTERVENTIONS: In epoch 1 the Ca2+:PO4 molar ratio of the PN formulation was ~1.3-1.5:1 (1.7 mmol Ca2+ and 1.1 mmol PO4 per 100 mL aqueous phase) and in epoch 2 was 1.0:1 via extra phosphate supplementation (1.7 mmol Ca2+ and 1.7 mmol PO4 per 100 mL). MAIN OUTCOME MEASURES: Peak calcium and nadir phosphate and potassium concentrations, and proportions with severe hypercalcaemia (Ca2+ >3.0 mmol/L), hypophosphataemia (PO4<1.5 mmol/L), and hypokalaemia (K+ <3.5 mmol/L) within the first postnatal week. RESULTS: In epoch 2, peak calcium concentrations were lower than in epoch 1 (geometric means: 2.83 mmol/L vs 3.09 mmol/L, p value<0.0001), fewer babies were severely hypercalcaemic (10/49, 20%, vs 31/51, 61%, p value<0.0001); nadir plasma phosphate concentrations were higher (means: 1.54 mmol/L vs 1.32 mmol/L, p value=0.006), and there were fewer cases of hypophosphataemia (17/49, 35% vs 31/51, 61%, p value=0.009) and hypokalaemia (12/49, 25% vs 23/51, 45%, p value=0.03). CONCLUSIONS: Reverting from a PN Ca2+:PO4 molar ratio of 1.3-1.5:1 to a ratio of 1.0:1 was associated with a lower incidence and severity of hypophosphataemia and hypercalcaemia. For preterm infants given higher concentrations of amino acids (≥2.5 g/kg/day) from postnatal day 1, an equimolar Ca2+:PO4 ratio may be preferable during the first postnatal week.

Diuretic, natriuretic and potassium-sparing effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats.

Active constituents from natural origin have long been used for the treatment of patients suffering from cardiovascular and renal diseases. This study therefore aimed to investigate the diuretic and natriuretic properties of nothofagin, a dihydrochalcone isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats. Male Wistar normotensive rats were orally treated with vehicle (1 ml/kg); hydrochlorothiazide (HCTZ; 25 mg/kg); ethyl acetate fraction from L. dasytricha (EALD; 3-30 mg/kg) and nothofagin (NOT; 0.3-3 mg/kg). Spontaneously hypertensive rats (SHR) received NOT (1 mg/kg), HCTZ (25 mg/kg) or vehicle. The cumulative diuretic index, urinary electrolytes excretion (Na+ and K+), pH, density and conductivity were measured at the end of the experiment (after 8 h). A7r5 and L929 cell lines were used to measure cell viability after exposure to NOT. Nitric oxide generation was quantified in A7r5 cell supernatant, and DPPH assay was used for evaluating the antioxidant properties of NOT. The urinary volume of normotensive rats were increased after the treatment with EALD, without any changes in Na+ or K+ excretion. NOT was able to induce diuresis and natriuresis, but not kaliuresis, in both normotensive and hypertensive rats. The reduction in prostanoids generation through cyclooxygenase inhibition, as well as the muscarinic receptor antagonism, fully avoided NOT-induced increases in diuretic index. NOT, which did not interfere with L929 or A7r5 cell viability, was able to stimulate nitric oxide generation in A7r5 cell, besides showing an antioxidant effect in scavenging the free-radical DPPH. Taken together, our study shows, for the first time, the diuretic, natriuretic and potassium-sparing effect of nothofagin in rats, which was associated with prostanoids generation, muscarinic receptor activation and antioxidant properties.

Clinical Utility of Potassium-Sparing Diuretics to Maintain Normal Serum Potassium in Peritoneal Dialysis Patients.

♦ BACKGROUND: Hypokalemia is a vexing problem in end-stage renal disease patients on peritoneal dialysis (PD), and oral potassium supplements (OPS) have limited palatability. Potassium-sparing diuretics (KSD) (spironolactone, amiloride) may be effective in these patients. ♦ METHODS: We performed a cross-sectional review of 75 current or past (vintage > 6 months) PD patients with regard to serum potassium (K+), OPS, and KSD utilization. We reviewed charts for multiple clinical and laboratory variables, including dialysis adequacy, residual renal function, nutritional status and co-existing medical therapy. ♦ RESULTS: The cohort was middle-aged with a mean age of 49.2 years (standard deviation [SD] = 14.7) and overweight with a body mass index of 29.5 (6.7) kg/m2. Of all the participants, 57.3% were female, 73.3% African-American, and 48% diabetic with an overall PD vintage of 28.2 (24.3) months at the time of enrollment. Weekly Kt/V was 2.12 (0.43), creatinine clearance was 73.5 (33.6) L/week/1.73 m2 with total daily exchange volume of 10.8 (2.7) L. Residual urine output (RUO) measured at 440 (494) mL (anuric 30.6%). Three-month averaged serum K+ measured at 4 (0.5) mmol/L with 36% of the participants receiving K+ supplements (median: 20 [0;20] mmol/day) and 41.3% KSD (spironolactone dose: 25 - 200 mg/day; amiloride dose: 5 - 10 mg/day). Serum K+ correlated positively with weekly Kt/V (r = 0.239; p = 0.039), PD vintage (r = 0.272; p = 0.018) but not with PD modality, daily exchange volume, RUO, or KSD use. However, KSD use was associated with decreased use of OPS (r = -0.646; p < 0.0001). ♦ CONCLUSIONS: Potassium-sparing diuretics were effective in this cohort of PD patients and decreased the need for OPS utilization.