Risk Factors For Hyperkalemia Research Articles

Association of serum sodium minus chloride level at initiation of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and hyperkalemia in patients with CKD: a case control study

Abstract Background Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) exert a renoprotective effect on patients with chronic kidney disease (CKD). Despite their benefit, one of their side effects is hyperkalemia, and it is one of the most common reasons for discontinuation of these drugs. Hyperchloremic metabolic acidosis is a known risk factor for hyperkalemia in patients with CKD. However, whether it is a risk factor for hyperkalemia after initiating ACE-I or ARB remains unclear. Methods In a previous study, serum sodium minus chloride level ([Na+) − (Cl−]) was identified as useful for diagnosing metabolic acidosis. To estimate the baseline acid–base status, we determined for the cutoff value of [Na+] − [Cl−] that correlates with [HCO3−] below 24 mEq/L in patients with CKD. We then investigated whether this cutoff value was associated with hyperkalemia (serum potassium level ≥ 5.0 mEq/L) after initiating ACE-I or ARB in patients with CKD. Results In the investigation of the cutoff value of [Na+] − [Cl−], 612 patients were examined, and [Na+] − [Cl−] showed a good correlation with [HCO3−] (r = 0.67, p < 0.001). Based on receiver operating curve analysis, we derived a cut-off value of [Na+] − [Cl−] below 33.5 mEq/L. Using this cut off value, the sensitivity and specificity of [Na+] − [Cl−] for metabolic acidosis were 75.2% and 75.0%, respectively. To explore whether metabolic acidosis is associated with hyperkalemia after initiating ACE-I or ARB, we examined 1143 patients with CKD. Among this cohort, 403 (35.3%) patients had [Na+] − [Cl−] < 33.5 mEq/L at baseline, and the incidence of hyperkalemia was significantly higher in univariate analysis (9.2% versus 4.2%, p = 0.03). However, in multivariate analysis, [Na+] − [Cl−] < 33.5 mEq/L was not associated with hyperkalemia (odds ratio 1.13; 95% confidence interval 0.65–1.95). Conclusions Hyperchloremic metabolic acidosis was not associated with hyperkalemia after initiation of ACE-I or ARB in patients with CKD.

Epidemiology and risk factors for hyperkalaemia in heart failure.

Patients with heart failure (HF), particularly those with impaired renal function receiving renin-angiotensin-aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+ ) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow-up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one-quarter to two-fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+ , 55-93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow-up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE-HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes.

The Prevalence and Risk Factors of Hyperkalemia in the Outpatient Setting.

Hyperkalemia is a life-threatening condition in outpatient and emergency departments. Hyperkalemia is associated with more events of major adverse cardiovascular diseases, hospitalization, and death. The aim of this study is to study and assess the prevalence and risk factors for developing hyperkalemia within the Thai population. A cross-sectional observational study of 3,299 unique adult patients (≥18 years) in one calendar year (2021) with at least 1 valid serum potassium (SK) test was conducted in the outpatient department of medicine. Hyperkalemia was determined as SK ≥5.8 mmol/L without hemolysis or technical error. Clinical data and laboratory tests were collected for analysis of risk factors. 2,971 patients (131 hyperkalemia and 2,840 control) were eligible. The annual prevalence of hyperkalemia was 4.41%. The mean ages of patients were 66.5 years in the hyperkalemia group and 55.9 years in the control group. Increasing age had a positive association (r = 0.220, p < 0.001) to risk of hyperkalemia, whereas the estimated glomerular filtration rate (eGFR) had an inverse association with SK level (r = -0.398, p < 0.001). The risk factors for hyperkalemia were patients with age ≥65 years (odds ratio, 2.106; 95% CI, 1.399, 3.171; p < 0.001), presence of diabetes mellitus (DM, odds ratio, 1.541; 95% CI, 1.030, 2.306; p = 0.036), chronic kidney disease (CKD) stage ≥3 (odds ratio, 14.885; 95% CI, 8.112, 27.313; p < 0.001), hemodialysis treatment (odds ratio, 10.170; 95% CI, 5.858, 17.657; p < 0.001), and usage of renin-angiotensin-aldosterone system inhibitors (RAASi, odds ratio, 2.256; 95% CI, 1.440, 3.536; p < 0.001). The risk factors contributing to hyperkalemia were patients with older age, DM, CKD, hemodialysis treatment, and usage of RAASi. Although the usage of RAASi is proven to be a cardiovascular advantage in the elderly, DM, and CKD patients, careful monitoring of SK is strongly advised to optimize patient care.

Gender-specific risk factors and outcomes of hyperkalemia in CKD patients: smoking as a driver of hyperkalemia in men.

Hyperkalemia is common among patients with chronic kidney disease (CKD) but there is scarce information on differential risk factors and outcomes for men and women. For instance, smoking has been suggested to be a risk factor for hyperkalemia, but specific analysis of the sex-specific impact of smoking on hyperkalemia in CKD is lacking. We studied serum potassium levels in 2891 participants from the NEFRONA cohort: 483 controls (47% women) and 2408 CKD patients (38% women) without prior cardiovascular disease (CVD), assessing whether smoking is a risk factor for hyperkalemia, and if hyperkalemia is associated with outcomes separately for men and women. Median potassium levels and prevalence of hypo and hyperkalemia were higher in CKD participants than in controls. Serum potassium levels were higher and hyperkalemia and severe hyperkalemia more prevalent in men than in women with non-dialysis CKD (G3-G5). The highest prevalence of hyperkalemia for each gender was found in CKD G4-G5 and hemodialysis patients for men (46%) and in hemodialysis (54%) for women. Gender-specific etiological multivariate analysis identified current smoking as a risk factor for hyperkalemia only in men. Hyperkalemia was independently associated with stopping RAASi, an outcome which was more common in women. Hyperkalemia was also associated to higher risk of cardiovascular events within 4 years in men. In conclusion, hyperkalemia is common among men and women with CKD, but the prevalence, risk factors and outcomes may differ by gender. Specifically, current smoking is a driver of hyperkalemia in men.

Effect of preparation method for radioactive iodine therapy on serum electrolytes.

Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT. From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134mmol/L) and hyperkalemia (serum potassium level ≥ 5.0mmol/L). Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019). THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.

Potentially Life-threatening Arrhythmia Triggered by an Excessive Consumption of Dried Sweet Potato "Hoshi-Imo".

We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of “Hoshi-Imo” (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of “Hoshi-Imo” may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.

MO443EFFECTS OF SHORT-TERM POTASSIUM CHLORIDE SUPPLEMENTATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE*

Abstract Background and Aims A high potassium (K+) diet is part of a healthy lifestyle and reduces blood pressure. Indeed, salt substitution (replacing NaCl by KCl) reduces the incidence of hypertension. Furthermore, emerging data show that high urinary K+ excretion in patients with chronic kidney disease (CKD) is associated with better kidney outcomes. This suggests that higher dietary K+ intake is also beneficial for patients with CKD, but a potential concern is hyperkalemia. Thus, there is a need for data on the effects of KCl supplementation in patients with CKD. Methods The effect of KCl supplementation (40 mEq/day) was studied by analyzing the 2-week open-label run-in phase of an ongoing randomized clinical trial studying the renoprotective effects of 2-year K+ supplementation in patients with progressive CKD and hypertension. The aims were to (1) analyze the effects of KCl supplementation on whole-blood K+ (WBK+) and acid-base balance, (2) identify factors associated with a rise in WBK+, and (3) identify risk factors for hyperkalemia (WBK+ &amp;gt; 5.5 mEq/L) . Results In 200 patients (68 ± 11 years, 74% males, eGFR 32 ± 9 mL/min/1.73 m2, 84% on renin-angiotensin inhibitors, 39% with diabetes mellitus), KCl supplementation increased urinary K+ excretion from 73 ± 24 to 106 ± 29 mEq/day, urinary chloride excretion from 144 ± 63 to 174 ± 60 mEq/day, WBK+ from 4.3 ± 0.5 to 4.7 ± 0.6 mEq/L, and plasma aldosterone from 294 to 366 ng/L (P &amp;lt; 0.01 for all). Plasma chloride increased from 104 ± 4 to 106 ± 4 mEq/L, while plasma bicarbonate decreased from 24.4 ± 3.4 to 23.6 ± 3.5 mEq/L and venous pH from 7.36 ± 0.03 to 7.34 ± 0.04 (P &amp;lt; 0.001 for all); urinary ammonium excretion did not increase (stable at 17.2 mEq/day). KCl supplementation had no significant effect on plasma renin (33 to 39 pg/mL), urinary sodium excretion (156 ± 63 to 155 ± 65 mEq/day), systolic blood pressure (134 ± 16 to 133 ± 17 mm Hg), eGFR (32 ± 9 to 31 ± 8 mL/min/1.73 m2) or albuminuria (stable at 0.2 g/day). Multivariable linear regression identified that age, female sex, and renin-angiotensin inhibitor use were associated with an increase in WBK+, while diuretic use, baseline WBK+, and baseline bicarbonate were inversely associated with a change in WBK+ after KCl supplementation (Table 1). The majority of patients (n = 181, 91%) remained normokalemic (WBK+ 4.6 ± 0.4 mEq/L). The 19 patients who did develop hyperkalemia (WBK+ 5.9 ± 0.4 mEq/L) were older (75 ± 8 vs. 67 ± 11 years), had lower eGFR (24 ± 8 vs. 32 ± 8 mL/min/1.73 m2), lower baseline bicarbonate (22.3 ± 3.6 vs. 24.6 ± 3.3 mEq/L), higher baseline WBK+ (4.8 ± 0.4 vs. 4.2 ± 0.4 mEq/L), and lower baseline urinary K+ excretion (64 ± 16 vs. 73 ± 25 mEq/day, P &amp;lt; 0.05 for all). Conclusions The majority of patients with advanced CKD remains normokalemic upon KCl supplementation, despite low eGFR, diabetes mellitus, or the use of renin-angiotensin inhibitors. This short-term study illustrates the feasibility of investigating the renoprotective potential of increased K+ intake or KCl-enriched salt in patients with CKD and provides the characteristics of patients in whom this is safe. Our study also shows that KCl supplementation causes a tendency towards metabolic acidosis, possibly by preventing an increase in ammoniagenesis. Longer-term studies are required to study the anti-hypertensive and renoprotective potential of K+ supplementation.

Risk factors associated with the incidence and recurrence of hyperkalaemia in patients with cardiorenal conditions.

Hyperkalaemia (HK) is associated with increased mortality risk. Prior studies suggest that the causes of HK are multifactorial. This study aimed to examine risk factors for incident and recurrent HK in six large real-world cohorts of UK patients that could be considered at elevated HK risk because of underlying disease pathology and/or medication use. This retrospective, observational cohort study utilised UK primary and secondary care data from Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES), respectively. Patients were included if they were aged ≥18years and had a record of ≥1 condition of interest (chronic kidney disease [CKD] stage 3+, heart failure, resistant hypertension [RHTN], dialysis, diabetes) and/or renin-angiotensin-aldosterone system inhibitors (RAASi) use between 01 January 2003 and 30 June 2018. Based on their diagnosis/ RAASi prescription record, patients were assigned to overlapping cohorts. The outcomes assessed were HK and recurrent HK, the latter defined as second or subsequent HK episode during follow-up. HK was defined as a serum K+ measurement ≥5.0mmol/L; thresholds of ≥5.5 and≥6.0mmol/L were also explored. Of 931460 meeting the eligibility criteria, 310535 (33.3%) patients experienced ≥1 HK event and 187719 (20.2%) experienced HK recurrence. The probability of subsequent HK events increased with event number from 60.5% for the second event to 76.5% for the sixth and the corresponding time to the next HK event decreased from 15.8months to 6.1months. Amongst the key risk factors, serum creatinine, serum phosphorus, systolic blood pressure, and white cell count demonstrated direct relationships with incidence and recurrence of HK, while inverse relationships were observed for estimated glomerular filtration rate (eGFR), haemoglobin and diastolic blood pressure. The relationship for Charlson's Comorbidity Index was mixed. The use of RAASi and anti-hyperglycaemic agents was associated with an increased risk of HK, while the use of diuretics (non-K+ -sparing) was protective against HK. Several risk factors for HK that are easily measured in routine clinical practice were identified, facilitating the identification of patients who are at the highest risk of experiencing HK, including recurrent HK.

Alteraciones graves del potasio plasmático: prevalencia, caracterización clínica-electrocardiográfica y su pronóstico

Introduction and objectivesExtracellular potassium (K+) concentrations play a crucial role in cell membrane electrophysiology. We aimed to determine the prevalence and clinical implications of severe serum K+ alterations in hospitalized patients. MethodsRetrospective study, of adult patients admitted to a tertiary hospital with severe dyskalemias (hypokalemia: K+ ≤ 2.5 mmol/L; hyperkalemia: K+ ≥ 6.5 mmol/L), for clinical characterization and prognostic evaluation. ResultsDuring 2013, 39 501 patients were hospitalized in our center, 603 had severe dyskalemias (0.6% hyperkalemia, 0.9% hypokalemia). Risk factors for hyperkalemia were renal dysfunction (72%) and use of renin angiotensin aldosterone inhibitors (22%); for hypokalemia were the use of diuretics, diet/low K+ intake and digestive losses. An electrocardiogram recording was obtained in 44% hyperkalemia and 26% hypokalemia patients. Presentation of severe arrhythmias was more frequent in hyperkalemia vs hypokalemia group (20% vs 6%; P = .01). In-hospital mortality was high in both groups (hyperkalemia 26% vs hypokalemia 19%; P = .04) and at 6 months (hyperkalemia 11% vs hypokalemia 16%; P = .13), as well as the severe recurrence rate at follow-up (hyperkalemia 28% vs hypokalemia 15%; P < .01). ConclusionsSevere dyskalemias are rare, but they are associated with poor prognosis. In-hospital mortality is high and is independently associated with significant comorbidity and increased arrhythmic events. Extensive electrocardiographic monitoring during hospitalization is recommended.

Risk factors for hyperkalemia in cirrhotic patients receiving spironolactone.

Objectives: To determine the factors those may predict hyperkalemia in cirrhotic patients receiving spironolactone. Study Design: Cross sectional descriptive study. Setting: Medicine Department Shalamar Hospital, Lahore. Period: 15 days from 1st September to 15th September 2017. Materials &amp; Methods: 150 patients with documented liver cirrhosis, receiving spironolactone and fulfilling the inclusion criteria were made part of the study. Five mL blood was drawn in two different vials; 2 mL in EDTA vial to check the prothrombin time (PT) and 3 mL in clotted vial to measure serum potassium, sodium, creatinine, urea, albumin, and bilirubin in serum after centrifugation. Potassium level was measured at baseline (Day-0) and two weeks later after receiving spironolactone. Results: Patients with raised serum creatinine (&gt;1.3 mg/dL) and hyperbilirubinemia (&gt;2.8 mg/dL) were found to have serum potassium more than 5 mmol/L. Increased potassium levels were found in patients receiving high dosage of spironolactone (&gt;100mg/day). These patients had decompensated liver cirrhosis as evident from their child-class C and significant hypoalbuminemia. Conclusion: Decompensated cirrhotic patients with raised serum creatinine, hyperbilirubinemia, hypoalbuminemia and receiving high dosage of spironolactone remain at higher risk of developing hyperkalemia.

Tailoring treatment of hyperkalemia.

Hyperkalemia is a common electrolyte disorder that may be rapidly life-threatening because of its cardiac toxicity. Hyperkalemia risk factors are numerous and often combined in the same patient. Most of the strategies to control serum potassium level in the short term have been used for decades. However, evidence for their efficacy and safety remains low. Treatment of hyperkalemia remains challenging, poorly codified, with a risk of overtreatment, including short-term side effects, and with the priority of avoiding unnecessary hospital stays or chronic medication changes. Recently, new oral treatments have been proposed for non-life-threatening hyperkalemia, with encouraging results. Their role in the therapeutic arsenal remains uncertain. Finally, a growing body of evidence suggests that hyperkalemia might negatively impact outcomes in the long term in patients with chronic heart failure or kidney failure through underdosing or withholding of cardiovascular medication (e.g. renin-angiotensin-aldosterone system inhibitors). Recognition of efficacy and potential side effects of treatment may help in tailoring treatments to the patient's status and conditions. In this review we discuss how treatment of hyperkalemia could be tailored to the patient's conditions and status, both on the short and mid term.

Trimethoprim-induced hyperkalemia in renal transplant recipient

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial agent used in a variety of infections. Adverse reactions are more common in patients with AIDS but occasionally occur in immunocompetent patients. Renal toxicity is usually a hypersensitivity reaction to the sulfa component and manifests as interstitial nephritis or sulfa crystallization in the renal tubules. Reversible hyperkalemia is a rarely reported side effect of TMP-SMX therapy attributed to TMP inhibition of potassium secretion in the distal renal tubule in a manner similar to the potassium-sparing diuretic, amiloride. We report a case of hyperkalemia associated with TMP-SMX occurring in a 32-year-old renal transplant recipient with no other risk factors for hyperkalemia. He was treated with TMP-SMX (800 mg + 160 mg) two tablets QID for suspected pneumocystis jiroveci pneumonia. He developed severe hyperkalemia on day 9 posttherapy. Hyperkalemia reverted to normal with withdrawal of trimethoprim.

Hyperkalemia in Combat Casualties: Implications for Delayed Evacuation.

Fixed facilities and rapid global evacuation ensured that delayed complications of trauma, such as hyperkalemia, occurred late in the evacuation chain where renal replacement therapies were available. However, future conflicts or humanitarian disasters may involve prolonged evacuation times. We sought to quantify one potential risk of delayed evacuation by assessing hyperkalemia in combat casualties. Retrospective study of military members admitted to intensive care units in Iraq and Afghanistan from February 1, 2002, to February 1, 2011. This study was approved by the U.S. Army Medical Research and Materiel Command Institutional Review Board. Demographics, injury severity score, burn injury, mechanism of injury, vital signs, creatinine, and potassium were collected. Logistic regression models were used to identify incidence and risk factors for hyperkalemia. Of 6,011 patient records, 1,472 had sufficient data to be included for analysis. Hyperkalemia occurred in 5.8% of patients. Those with hyperkalemia had higher injury severity scores, higher shock index, were more likely to have acute kidney injury, and were more likely to die. On multivariate analysis, acute kidney injury and shock index were significantly associated with the development of hyperkalemia. In a subgroup of patients with data on creatine kinase, rhabdomyolysis was associated with hyperkalemia in the univariate model, but was not significant after adjustment. Hyperkalemia occurred in 5.8% of patients in our cohort of critically injured combat casualties. The development of hyperkalemia was independently associated with acute kidney injury and shock index. In future conflicts, with prolonged evacuation times, mitigation strategies should be developed to treat hyperkalemia in casualties before arrival at definitive care.

Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes.

Abnormalities of serum potassium are common in patients with CKD. Although hyperkalemia is a well-recognized complication of CKD, the prevalence rates of hyperkalemia (14%-20%) and hypokalemia (12%-18%) are similar. CKD severity, use of medications such as renin-angiotensin-aldosterone system inhibitors and diuretics, and dietary potassium intake are major determinants of serum potassium concentration in CKD. Demographic factors, acid-base status, blood glucose, and other comorbidities contribute as well. Both hyperkalemia and hypokalemia are associated with similarly increased risks of death, cardiovascular disease, and hospitalization. On the other hand, limited evidence suggests a link between hypokalemia, but not hyperkalemia, and progression of CKD. This article reviews the prevalence rates and risk factors for hyperkalemia and hypokalemia, and their associations with adverse outcomes in CKD.

Effect of Patiromer on Serum K+ in Hyperkalemic Patients with Heart Failure (HF): Pooled Results From the AMETHYST-DN, OPAL-HK and TOURMALINE Trials

Introduction: Hyperkalemia (HK), typically defined as serum potassium (K+) >5.0 mmol/L, may cause serious, potentially fatal arrhythmias. Patients with heart failure (HF) are prone to arrhythmias and at risk for HK due to underlying chronic kidney disease (CKD), NSAID's and/or use of guideline-recommended renin angiotensin-aldosterone system inhibitors (RAASi). Patiromer, a non-absorbed, sodium-free, K+ binder, is indicated for the treatment of HK in the U.S. We evaluated patiromer's effect on serum K+ in patients with HK and HF using data from three clinical trials. Methods: The effect of four weeks' treatment with patiromer on serum K+ was investigated by combining data from three studies: AMETHYST-DN (A-DN), OPAL-HK (OP) and TOURMALINE (TOUR). Eligible patients had to have risk factors for HK at entry and (local lab) serum K+ > 5.0 mmol/L to receive patiromer. Starting doses of patiromer ranged from 8.4 to 33.6 g/d. The diagnosis of HF was based on investigator opinion. Only patients who took more than one dose of patiromer and were evaluable for efficacy were included in this post-hoc analysis. Data were pooled and analysed for change from baseline in serum K+ (primary endpoint in OP and A-DN; secondary endpoint in TOUR). Results: Of 653 patients included in the analysis, 62% were men, the mean age was 66 (SD 10) and serum K+ was 5.4 (SD 0.4) mmol/L at baseline. Patient characteristics were not substantially different between the 214 patients who had HF and the 439 who did not. Mean serum K+ fell below 5.0 mmol/L within one week of starting patiromer to reach a nadir of 4.6 mmol/L at three weeks for those with and without HF (Figure). By week four, least square mean (95% CI) serum K+ change from baseline was -0.79 (-0.91, -0.68) mmol/L in those with HF and -0.75 (-0.79, -0.70) mmol/L in those without HF, and serum K+ fell below 3.5 mmol/L in 2 (0.9%) patients with and in 8 (1.8%) patients without HF. Adverse events (AEs) occurred in 27.1% of those with and in 34.4% of those without HF. The most common AEs were constipation (in 7.0% of patients with and in 5.5% of patients without HF) and diarrhea (in 1.4% of patients with and in 3.6% of patients without HF); all cases were mild or moderate. AEs led to patiromer discontinuation in 5.1% of those with and in 3.0% of those without HF. Conclusions: Patiromer reduced serum K+ similarly over four weeks in patients with HK whether or not they had HF and this was consistent across the individual studies.

Hyperkalemia: current concepts and emerging therapeutic options

H yperkalemia has long constituted one of the electrolyte abnormalities of interest to clinicians and physiologists, and it represents one of the most important acute electrolyte abnormalities due to its potential for causing life-threatening arrhythmias. Hyperkalemia remains a vexing and challenging problem for clinicians, particularly in the management of patients with chronic kidney disease and cardiovascular disease, especially congestive heart failure. In the past 2 decades, themedical community has witnessed a major increase in its understanding of the physiology of renal potassium handling and the relatively unappreciated role of extrarenal and gut sensors in modulating renal potassium handling. This increased understanding has enhanced the diagnosis of dyskalemias. In recent years, increasing investigative attention has focused on novel physiological paradigms that increase not only the complexity but also the precision of homeostasis. These fundamental investigative breakthroughs have been coupled with a reassessment of the expanding spectrum of clinical disorders that predispose to the development of hyperkalemia. The overriding importance of renin– angiotensin–aldosterone system inhibitors (RAASis) as risk factors of hyperkalemia has been increasingly appreciated. A careful reading of the articles of this supplement should provide clinicians with the information needed to more rationally manage the clinical disorders of dyskalemia with an emphasis on hyperkalemia. The contributors to this supplement were asked to review critically the available literature dealing with specific facets of the normal physiology of renal potassium handling and derangements of renal modulation of potassium that result in diverse dyskalemic disorders. The first article, by Csaba Kovesdy, MD, surveys the epidemiology of hyperkalemia. He examines the currently known incidence and

Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Incident hyperkalemia may be an independent therapeutic target in low ejection fraction heart failure patients: Insights from the HEAAL study

BackgroundAngiotensin receptor antagonists (ARBs) improve outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction, but may induce hyperkalemia (HK) and/or a worsening of renal function (WRF). Methods and resultsThe incidence and risk factors of HK and its inter-relationship with WRF, as well as associations with clinical outcome (death or admission for HF i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL trial (losartan 150mg/d vs. 50mg/d) were assessed. Worsening of renal function was defined as a decrease in eGFR >20% from baseline and HK as serum K >5.5 or >5mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK >5mmol/L or WRF occurred at least once in about half of the patients. WRF was associated with higher occurrence of HK (HR 1.19 (1.06–1.34)) and vice versa (HR 1.35 (1.19–1.53)), but preceded HK in only about half of the events. High dose losartan improved outcome despite more frequent WRF and HK, both being independently associated with adverse outcomes in multivariate analyses. ConclusionsHK and WRF are common in HF patients. Both can be predicted from baseline risk factors and are therefore potentially preventable. Although associated with worse outcome, occurrence of any does not hinder the efficacy of high dose losartan. HK was associated with WRF and worse outcomes. Whether therapy targeting specifically HK may maximize the survival benefit derived from renin angiotensin aldosterone inhibitor use should be appropriately tested in future trials.

Incidence and factors of post-adrenalectomy hyperkalemia in patients with aldosterone producing adenoma

BackgroundHyperkalemia is a potentially serious complication following adrenalectomy of aldosterone-producing adenomas (APA). We analyzed the incidence and risk factors for hyperkalemia after adrenalectomy in patients with APA. MethodsWe retrospectively analyzed the records of 55 patients who underwent adrenalectomy for APA between 2002 and 2011. Demographic features, biochemical and hormonal profiles, imaging, and relevant medications were reviewed. ResultsSixteen of 55 APA patients (29.1%) developed hyperkalemia (mean serum K+ 5.6±0.3mmol/l) after adrenalectomy and 3 had persistent hyperkalemia requiring mineralocorticoid supplementation for more than nine months. Compared with normokalemic patients, hyperkalemic patients were characterized by male predominance, older age, longer duration of hypertension (12.8±9.3 vs. 6.7±5.0 y, p<0.05), lower nadir serum K+ (p<0.05), higher preoperative serum creatinine (p<0.01), and higher likelihood of residual hypertension. Using multivariate regression analysis, longer duration of hypertension and impaired renal function were the most important factors of post-adrenalectomy hyperkalemia. ConclusionsPost-adrenalectomy hyperkalemia in patients with APA is not rare and associated with impaired renal function and longer duration of hypertension. Serum K+ must be cautiously monitored in patients with long-term hypertension and kidney disease.

INCIDENT HYPERKALEMIA IS AN INDEPENDENT THERAPEUTIC TARGET IN LOW EJECTION FRACTION HEART FAILURE PATIENTS. INSIGHTS FROM THE HEAAL STUDY

article i nfo Background: Angiotensin receptor antagonists (ARBs) improve outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction, but may induce hyperkalemia (HK) and/or a worsening of renal func- tion (WRF). Methods and results: The incidence and risk factors of HK and its inter-relationship with WRF, as well as associa- tions with clinical outcome (death or admission for HF i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL trial (losartan 150 mg/d vs. 50 mg/d) were assessed. Worsening of renal function was defined as a decrease ineGFRN20% from baseline and HK as serum K N5.5 or N5 mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK N5 mmol/L or WRF occurred at least once in about half of the patients. WRF was associated with higher occurrence of HK (HR 1.19 (1.06-1.34)) and vice versa (HR 1.35 (1.19-1.53)), but preceded HK in only about half of the events. High dose losartan improved outcome despite morefrequentWRFandHK,bothbeingindependentlyassociatedwithadverseoutcomesinmultivariateanalyses. Conclusions: HK and WRF are common in HF patients. Both can be predicted from baseline risk factors and are therefore potentially preventable. Although associated with worse outcome, occurrence of any does not hinder the efficacy of high dose losartan. HK was associated with WRF and worse outcomes. Whether therapy targeting specifically HK may maximize the survival benefit derived from renin angiotensin aldosterone inhibitor use should be appropriately tested in future trials.