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1.
J Cardiovasc Med (Hagerstown) ; 25(8): 613-622, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949149

RESUMO

BACKGROUND: New trials indicated a potential of sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce hyperkalemia, which might have important clinical implications, but real-world data are limited. Therefore, we examined the effect of SGLT2i on hyper- and hypokalemia occurrence using the FDA adverse event reporting system (FAERS). METHODS: The FAERS database was retrospectively queried from 2004q1 to 2021q3. Disproportionality analyses were performed based on the reporting odds ratio (ROR) and 95% confidence interval (CI). RESULTS: There were 84 601 adverse event reports for SGLT2i and 1 321 186 reports for other glucose-lowering medications. The hyperkalemia reporting incidence was significantly lower with SGLT2i than with other glucose-lowering medications (ROR, 0.83; 95% CI, 0.79-0.86). Reductions in hyperkalemia reports did not change across a series of sensitivity analyses. Compared with that with renin-angiotensin-aldosterone system inhibitors (RAASi) alone (ROR, 4.40; 95% CI, 4.31-4.49), the hyperkalemia reporting incidence was disproportionally lower among individuals using RAASi with SGLT2i (ROR, 3.25; 95% CI, 3.06-3.45). Compared with that with mineralocorticoid receptor antagonists (MRAs) alone, the hyperkalemia reporting incidence was also slightly lower among individuals using MRAs with SGLT-2i. The reporting incidence of hypokalemia was lower with SGLT2i than with other antihyperglycemic agents (ROR, 0.79; 95% CI, 0.75-0.83). CONCLUSION: In a real-world setting, hyperkalemia and hypokalemia were robustly and consistently reported less frequently with SGLT2i than with other diabetes medications. There were disproportionally fewer hyperkalemia reports among those using SGLT-2is with RAASi or MRAs than among those using RAASi or MRAs alone.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Hiperpotassemia , Hipopotassemia , Farmacovigilância , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Hiperpotassemia/sangue , Hiperpotassemia/diagnóstico , Estudos Retrospectivos , Hipopotassemia/induzido quimicamente , Hipopotassemia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Incidência , Idoso , Potássio/sangue , Bases de Dados Factuais , Estados Unidos/epidemiologia , Fatores de Risco , Biomarcadores/sangue , Medição de Risco , Resultado do Tratamento
2.
J Med Case Rep ; 18(1): 273, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38851740

RESUMO

BACKGROUND: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure. CASE PRESENTATION: A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab. CONCLUSION: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures.


Assuntos
Bradicardia , Digoxina , Hiperpotassemia , Diálise Renal , Humanos , Feminino , Idoso , Digoxina/efeitos adversos , Hiperpotassemia/induzido quimicamente , Bradicardia/induzido quimicamente , Insuficiência Renal/induzido quimicamente , Antiarrítmicos/efeitos adversos , Síndrome , Acidose/induzido quimicamente , Choque/induzido quimicamente , Bloqueio Atrioventricular/induzido quimicamente , Fragmentos Fab das Imunoglobulinas
3.
Sr Care Pharm ; 39(7): 259-266, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38937893

RESUMO

The objective of this analysis is to investigate the risk of hyperkalemia in hospitalized patients using sulfamethoxazole-trimethoprim (Co-trimoxazole) and a potassium-sparing drug (potassium-sparing diuretic or renin-angiotensin system [RAS]-inhibitor). Researchers conducted a nested case control study within a cohort of hospitalized patients using a potassium-sparing diuretic and/or a RAS-inhibitor from the PHARMO Database Network. Researchers estimated the odds ratios (ORs) and 95% confidence intervals (CI) for the risk of hyperkalemia in patients receiving both Co-trimoxazole and a potassium-sparing drug compared with patients only receiving a potassium-sparing drug. Among a cohort of 25,849 patients, researchers identified 2054 cases of hyperkalemia during hospitalization in patients also using a potassium-sparing drug. Using Co-trimoxazole in addition to a potassium-sparing drug was associated with an increased risk of hyperkalemia in hospitalized patients (ORadj = 1.65, 95% CI 1.26-2.16) compared with using only a potassium-sparing drug. There was a trend of a more pronounced association between hyperkalemia and the co-use of Co-trimoxazole and potassium-sparing drugs in patients with an estimated GFR of 15-29 mL/min (ORadj = 3.15, 95% CI 1.29-7.70). The number needed to harm for hyperkalemia induced by adding Co-trimoxazole to patients receiving a potassium-sparing drug is 19.5. Using the combination of Co-trimoxazole with a potassium-sparing drug in hospitalized patients increases the risk of hyperkalemia compared with using only a potassium-sparing drug. Physicians and other prescribers should be aware of hyperkalemia and routinely monitor serum potassium levels in hospitalized patients using this combination of drugs.


Assuntos
Hospitalização , Hiperpotassemia , Combinação Trimetoprima e Sulfametoxazol , Hiperpotassemia/induzido quimicamente , Humanos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos de Casos e Controles , Diurético Poupador de Potássio/efeitos adversos , Diurético Poupador de Potássio/uso terapêutico , Estudos de Coortes , Idoso de 80 Anos ou mais , Potássio/sangue , Adulto
4.
BMJ ; 385: e078483, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38925801

RESUMO

OBJECTIVES: To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice. DESIGN: Population based cohort study with active-comparator, new user design. SETTING: Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022. PARTICIPANTS: 1:1 propensity score matched adults with type 2 diabetes newly starting SGLT-2 inhibitors versus DPP-4 inhibitors (n=778 908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729 820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873 460). MAIN OUTCOME MEASURES: Hyperkalemia diagnosis in the inpatient or outpatient setting. Secondary outcomes were hyperkalemia defined as serum potassium levels ≥5.5 mmol/L and hyperkalemia diagnosis in the inpatient or emergency department setting. RESULTS: Starting SGLT-2 inhibitor treatment was associated with a lower rate of hyperkalemia than DPP-4 inhibitor treatment (hazard ratio 0.75, 95% confidence interval (CI) 0.73 to 0.78) and a slight reduction in rate compared with GLP-1 receptor agonists (0.92, 0.89 to 0.95). Use of GLP-1 receptor agonists was associated with a lower rate of hyperkalemia than DPP-4 inhibitors (0.79, 0.77 to 0.82). The three year absolute risk was 2.4% (95% CI 2.1% to 2.7%) lower for SGLT-2 inhibitors than DPP-4 inhibitors (4.6% v 7.0%), 1.8% (1.4% to 2.1%) lower for GLP-1 receptor agonists than DPP-4 inhibitors (5.7% v 7.5%), and 1.2% (0.9% to 1.5%) lower for SGLT-2 inhibitors than GLP-1 receptor agonists (4.7% v 6.0%). Findings were consistent for the secondary outcomes and among subgroups defined by age, sex, race, medical conditions, other drug use, and hemoglobin A1c levels on the relative scale. Benefits for SGLT-2 inhibitors and GLP-1 receptor agonists on the absolute scale were largest for those with heart failure, chronic kidney disease, or those using mineralocorticoid receptor antagonists. Compared with DPP-4 inhibitors, the lower rate of hyperkalemia was consistently observed across individual agents in the SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) and GLP-1 receptor agonist (dulaglutide, exenatide, liraglutide, semaglutide) classes. CONCLUSIONS: In people with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of hyperkalemia than DPP-4 inhibitors in the overall population and across relevant subgroups. The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hiperpotassemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Masculino , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Idoso , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Estudos de Coortes , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Pontuação de Propensão , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon
5.
Drug Metab Pharmacokinet ; 56: 101019, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38797092

RESUMO

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.


Assuntos
Nefropatias Diabéticas , Desenvolvimento de Medicamentos , Hiperpotassemia , Antagonistas de Receptores de Mineralocorticoides , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/diagnóstico , Nefropatias Diabéticas/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Desenvolvimento de Medicamentos/métodos , Estudos Prospectivos , Farmacologia em Rede , Ensaios Clínicos como Assunto/métodos
6.
J Am Heart Assoc ; 13(9): e033236, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38686902

RESUMO

BACKGROUND: Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. METHODS AND RESULTS: We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. CONCLUSIONS: Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.


Assuntos
Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Potássio , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Pessoa de Meia-Idade , Potássio/sangue , Taiwan/epidemiologia , Idoso , Fatores de Risco , Biomarcadores/sangue , Medição de Risco , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/sangue , Hiperpotassemia/epidemiologia , Rim/fisiopatologia , Rim/efeitos dos fármacos , Estudos Retrospectivos , Hipopotassemia/induzido quimicamente , Hipopotassemia/sangue , Hipopotassemia/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico
7.
Artigo em Inglês | MEDLINE | ID: mdl-38511807

RESUMO

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.


Assuntos
Acidose , Hiperpotassemia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/induzido quimicamente , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/complicações , Hiperpotassemia/tratamento farmacológico , Acidose/induzido quimicamente , Acidose/complicações , Acidose/tratamento farmacológico , Rim , Estudos Retrospectivos
8.
Cardiorenal Med ; 14(1): 191-201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38513618

RESUMO

BACKGROUND: According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group. SUMMARY: Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi. KEY MESSAGES: It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperpotassemia , Naftiridinas , Insuficiência Renal Crônica , Sistema Renina-Angiotensina , Humanos , Hiperpotassemia/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos
9.
Clin Toxicol (Phila) ; 62(1): 46-52, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38421360

RESUMO

INTRODUCTION: Oral potassium poisoning can be life-threatening. The study aimed to describe patterns of oral potassium poisoning in adult and pediatric populations and characterize its clinical presentation and management as reported by United States poison centers. METHODS: This is a retrospective review of the National Poison Data System from 1 January 2010 through 30 June 2021. We descriptively analyzed cases involving single substance, oral potassium salts. In a second step, we requested a subset of case-specific narratives for cases that resulted in major outcome or death, as well as cases where patients received any of the following therapies: whole bowel irrigation, sodium bicarbonate, calcium, insulin or hemodialysis. We classified hyperkalemia by expected toxicity: mild (peak potassium concentration <6.5 mEq/L), moderate (peak potassium concentration 6.5 to <8 mEq/L) or severe (peak potassium concentration ≥ 8mEq/L). RESULTS: The National Poison Data System included 1,820 cases, 52.3 percent being adults. Among adult cases, 20% (n = 189) resulted in a moderate effect, major effect or death. Among pediatric cases aged <10 years, all exposures were unintentional. Analysis of 49 case narratives showed a median peak potassium concentration of 7.1 mEq/L (interquartile range 5.4-8.6) and a moderate correlation with the dose ingested (r = 0.66). Severe hyperkalemia was associated with QRS complex widening (P < 0.001), peaked T-waves (P = 0.001), and neurological symptoms (P = 0.04). Whole bowel irrigation was associated with mild hyperkalemia (P = 0.011), and hemodialysis was associated with severe hyperkalemia (P < 0.001). DISCUSSION: Analysis of data showed that therapy to promote intracellular shift of potassium is the mainstay of management of oral potassium poisoning, followed by hemodialysis. LIMITATIONS: Poison center data are susceptible to reporting bias. National Poison Data System data are affected by completeness and accuracy of reporting from health care providers and the lay public. CONCLUSIONS: Single substance, oral potassium poisoning, reported to United States poison centers, is mostly unintentional and rarely results in hyperkalemia.


Assuntos
Hiperpotassemia , Venenos , Adulto , Humanos , Criança , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Hiperpotassemia/terapia , Estudos Retrospectivos , Potássio , Pessoal de Saúde
10.
Ren Fail ; 46(1): 2313864, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38345037

RESUMO

This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.


Assuntos
Anemia , Hiperpotassemia , Hipertensão , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Inibidores de Prolil-Hidrolase/efeitos adversos , Prolil Hidroxilases , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Anemia/tratamento farmacológico , Anemia/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Hipertensão/complicações , Rim , Hipóxia/complicações
11.
A A Pract ; 18(3): e01760, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38411589

RESUMO

A 63-year-old man with stage 3a chronic kidney disease (CKD) and mild hyperkalemia was scheduled for a robot-assisted prostatectomy. He was being treated with lisinopril. Owing to mild hyperkalemia (6.2 mmol/L), lisinopril was discontinued, and sodium polystyrene sulfonate was administered on the day before surgery. Three hours after incision, electrocardiographic signs of hyperkalemia manifested with the serum potassium concentration rising to 8 mmol/L. Although hyperkalemia is a common and well-documented side effect of angiotensin-converting enzyme inhibitors in patients with CKD, we report an extreme increase in potassium within a very short time period despite prior drug discontinuation.


Assuntos
Hiperpotassemia , Insuficiência Renal Crônica , Robótica , Masculino , Humanos , Pessoa de Meia-Idade , Hiperpotassemia/induzido quimicamente , Lisinopril , Prostatectomia/efeitos adversos , Potássio , Insuficiência Renal Crônica/complicações
12.
Pediatr Nephrol ; 39(8): 2325-2335, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38233719

RESUMO

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient.


Assuntos
Hidratação , Hiponatremia , Solução Salina , Humanos , Hidratação/métodos , Hidratação/efeitos adversos , Hiponatremia/prevenção & controle , Hiponatremia/etiologia , Solução Salina/administração & dosagem , Criança , Acidose/prevenção & controle , Acidose/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/induzido quimicamente , Hiperpotassemia/etiologia , Hiperpotassemia/prevenção & controle , Hiperpotassemia/induzido quimicamente
13.
CPT Pharmacometrics Syst Pharmacol ; 13(2): 296-307, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38050337

RESUMO

Potassium (K+ ) is the main intracellular cation in the body. Elevated K+ levels (hyperkalemia) increase the risk of life-threatening arrhythmias and sudden cardiac death. However, the details of K+ homeostasis and the effects of orally administered K+ binders, such as sodium zirconium cyclosilicate (SZC), on K+ redistribution and excretion in patients remain incompletely understood. We built a fit-for-purpose systems pharmacology model to describe K+ homeostasis in hyperkalemic subjects and capture serum K+ (sK+ ) dynamics in response to acute and chronic administration of SZC. The resulting model describes K+ distribution in the gastrointestinal (GI) tract, blood, and extracellular and intracellular spaces of tissue, renal clearance of K+ , and K+ -SZC binding and excretion in the GI tract. The model, which was fit to time-course sK+ data for individual patients from two clinical trials, accounts for bolus delivery of K+ in meals and oral doses of SZC. The virtual population of patients derived from fitting the model to these trials was then modified to predict the SZC dose-response and inform clinical trial design in two new applications: emergency lowering of sK+ in severe hyperkalemia and prevention of hyperkalemia between dialysis sessions in patients with end-stage chronic kidney disease. In both cases, the model provided novel and useful insight that was borne out by the now completed clinical trials, providing a concrete case study of fit-for-purpose, model-informed drug development after initial approval of a drug.


Assuntos
Hiperpotassemia , Falência Renal Crônica , Silicatos , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Preparações Farmacêuticas , Potássio/uso terapêutico , Homeostase
14.
Clin Ther ; 46(1): 40-49, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37953077

RESUMO

PURPOSE: It takes 17 years, on average, for trial results to be implemented into practice. Using data from the Department of Veterans Affairs (VA), this study assessed the potential impact on clinical practice of the dissemination of findings from a randomized, controlled trial reporting harm with the use of combination therapy. Communication between research and VA Pharmacy Benefits Management Services (PBM)  provided the impetus for communication from the PBM about the findings of the trial in accordance with policy. METHODS: In this de-implementation study, interrupted time series analysis was used for assessing prescribing patterns and adverse clinical events before and after the dissemination of the trial findings. The de-implementation strategy was multicomponent and multilevel. Strategies were aligned with categories outlined in the Expert Recommendations for Implementing Change: train and educate stakeholders, use evaluative and iterative strategies, develop stakeholder inter-relationships, change infrastructure, provide interactive assistance, and engage consumers. VA patients with type 2 diabetes mellitus, chronic kidney disease stages 1 to 3, and a moderate or severe albuminuria who received care between July 2008 and November 2017 were included. Patients were subgrouped according to treatment with an angiotensin-converting enzyme inhibitor + angiotensin receptor blocker. The primary end point was the prevalence of combination therapy use. Secondary end points were the incidences of acute kidney injury and hyperkalemia. FINDINGS: This study followed 712,245 patients, 9297 of whom used combination therapy. Data were available from 428,535 and 283,710 patients pre- and post-intervention, respectively; among these, 8324 and 973 patients used combination therapy, the median ages were 66 and 68 years, and 96.92% and 98.82% were men. One month following communication from the PBM, the reductions in combination therapy users, acute kidney injury events, and hyperkalemia were 331.94 (95% CI, 500.27-163.32), 36.58% (95% CI, 31.90%-41.95%), and 25.49% (95% CI, 14.17%-36.07%) per 100,000 patients per month, respectively (all, P < 0.001), whereas before the communication, these changes were +14.84 (95% CI, 10.27-19.42), -3.46% (95% CI, 3.18-3.74), and -3.27% (95% CI, 2.66%-3.87%) (all, P < 0.001). IMPLICATIONS: The apparent speed and impact of the implementation of changes resulting from the dissemination of trial findings into VA clinical practice are encouraging. The speed of implementation was much faster than average for health care providers in the United States. Established communications between research and clinical practice, as well as established policy and communications between PBM and clinical practice, may be a model for other health care organizations.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Hiperpotassemia , Masculino , Humanos , Estados Unidos , Idoso , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/complicações , Hiperpotassemia/epidemiologia , Análise de Séries Temporais Interrompida , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia
15.
Eur Heart J Cardiovasc Pharmacother ; 10(1): 45-52, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37942588

RESUMO

AIMS: To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). CONCLUSION: Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Hiperpotassemia , Hipopotassemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Transportador 2 de Glucose-Sódio , Hiperpotassemia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Hipopotassemia/diagnóstico , Hipopotassemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Potássio
16.
Am J Nephrol ; 55(1): 1-17, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37793348

RESUMO

BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.


Assuntos
Injúria Renal Aguda , Hiperpotassemia , Hipotensão , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Albuminúria/induzido quimicamente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Edema
17.
Heart Fail Rev ; 29(1): 207-217, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37917192

RESUMO

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.


Assuntos
Injúria Renal Aguda , Cetoacidose Diabética , Fraturas Ósseas , Insuficiência Cardíaca , Hiperpotassemia , Hipoglicemia , Hipopotassemia , Humanos , Volume Sistólico , Cetoacidose Diabética/induzido quimicamente , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Glucose
18.
Clin Exp Nephrol ; 28(2): 125-135, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37847437

RESUMO

BACKGROUND: Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy. This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns. CONCLUSION: Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperpotassemia , Insuficiência Renal Crônica , Animais , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Naftiridinas/efeitos adversos , Diabetes Mellitus Tipo 2/complicações
19.
Int J Cardiol ; 397: 131613, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38030039

RESUMO

BACKGROUND: Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. METHODS: We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. RESULTS: The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59-77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). CONCLUSIONS: In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults.


Assuntos
Injúria Renal Aguda , Angioedema , Insuficiência Cardíaca , Hiperpotassemia , Hipotensão , Humanos , Idoso , Estudos Retrospectivos , Tetrazóis/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Farmacovigilância , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/diagnóstico , Hiperpotassemia/epidemiologia , Inibidores da Enzima Conversora de Angiotensina , Valsartana/efeitos adversos , Aminobutiratos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/induzido quimicamente , Combinação de Medicamentos , Hipotensão/induzido quimicamente , Hipotensão/diagnóstico , Hipotensão/epidemiologia , Angioedema/induzido quimicamente , Angioedema/diagnóstico , Angioedema/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Volume Sistólico
20.
Clin Endocrinol (Oxf) ; 100(3): 278-283, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38127445

RESUMO

OBJECTIVE: Spironolactone (SPL) has been used to manage hyperandrogenic manifestations in women with polycystic ovary syndrome (PCOS), but data on the risk of hyperkalemia in this population are scarce. The aim of this study was to evaluate the incidence of hyperkalemia in women with PCOS using SPL in the long term. DESIGN: Single-centre retrospective study. PATIENTS: Inclusion and analysis of 98 treatment periods in 78 women with PCOS (20 of whom were duplicates, returning after treatment interruption for a mean of 38 months) who received SPL for a minimum of 12 months and had at least three measurements of potassium levels over time. MEASUREMENTS: Clinical and hormonal profiles before and during SPL treatment. RESULTS: Mean age was 29.1 (SD: 9.6) years, and body mass index was 32.2 (SD: 8.1) kg/m². Nine patients had diabetes, and 22 had prediabetes. SPL was used in combination with combined oral contraceptive pills in 55 participants and progestin-only pills/long-acting reversible contraception in 28; metformin was added in 35, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in 15. Median SPL dose was 100 (range: 50-150) mg. A total of 327 serum potassium measurements were obtained (84 pre-exposure and 243 postexposure). Four potassium measurements were above the reference range before exposure and 19 during exposure. All potassium measurements above the reference range during follow-up were classified as mild hyperkalemia (5.1-5.5 mEq/L). CONCLUSIONS: The present findings suggest that women with PCOS, without kidney or heart disease, using SPL combined with hormonal contraception for managing clinical hyperandrogenism have a low incidence of hyperkalemia and well-tolerated minor adverse effects.


Assuntos
Hiperpotassemia , Síndrome do Ovário Policístico , Potássio , Espironolactona , Adulto , Feminino , Humanos , Hirsutismo , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/complicações , Hiperpotassemia/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Potássio/sangue , Estudos Retrospectivos , Espironolactona/efeitos adversos
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