The impact of chronic kidney disease on medication choice and pharmacologic management in patients with heart failure

Introduction: In the past few years, medical community, including doctors, have become increasingly aware of the fact that chronic kidney disease (CKD) and heart failure (HF) have common risk factors which impact one another in terms of choice of therapy.

Areas covered: Management of these two diseases has been a challenge for physicians. The treatment goals for HF patients with CKD are very important. They serve as the end point in using a specific treatment for management and treatment of CKD patients, hence decreasing mortality rates. In this review, we discuss the pharmacological approaches to managing patients with HF and CKD, discussing current evidence-based up-to-date management strategies and guidelines in the general population with HF and CKD.

Expert commentary: Newer novel drugs targeting specific signaling pathways are approaching the stages of clinical investigation including the direct renin inhibitors. They have been a highly attractive concept for the future in the management of these patients. However, while advances in technology elucidated many aspects of these diseases, many mysteries still remain. With continued research, we can expect more cost-effective and patient-friendly drug therapies to be developed in the near future.     

Effect of dosing frequency on chronic cardiovascular disease medication adherence

Abstract

Background:

Many cardiovascular diseases (CVDs) require patients to take one or more long term medications, often administered multiple times a day. We sought to determine the effect of chronic CVD medication dosing frequency on medication adherence.     

老年慢性肾脏病患者肾脏不适当用药评价

目的:调查分析老年慢性肾脏病(chronic kidney disease, CKD)患者肾脏不适当用药(renally inappropriate medication, RIM)情况及危险因素,为指导老年CKD患者合理用药提供参考。方法:依据Beers标准(2019版),对2016年1月至2020年12月入住北京市某三甲医院的老年CKD患者RIM情况进行回顾性分析,采用多因素Logistic回归分析确定RIM的危险因素。结果:研究共纳入4 835例患者,其中595例(12.31%)存在RIM共662项,占比在前3位的药物是螺内酯(69.49%)、磺达肝癸钠(6.65%)和利伐沙班(4.68%)。Logistic回归分析显示,CKD4期及以上、住院时间≥20 d、用药品种数≥10种和心力衰竭是老年CKD住院患者发生RIM的独立危险因素。结论:老年CKD住院患者RIM发生率较高,患者用药合理性有待提升。用药品种数、住院天数、CKD分期和心力衰竭是患者发生RIM的危险因素,临床医师及药师应予以重视。     

The relative dosing of epoetin alfa and darbepoetin alfa in chronic kidney disease

ABSTRACT

Objective: The purpose of this study was to review and analyze current research to evaluate the dose ratio of epoetin alfa and darbepoetin alfa for the treatment of anemia in chronic kidney disease (CKD) and to identify determinants of the variation in epoetin alfa: darbepoetin alfa dose ratios across studies.

Methods: A systematic review of the literature for comparative switch and non-switch studies of epoetin alfa and darbepoetin alfa treatments in CKD for the period 2000–2005 was performed. Two reviewers independently assessed the quality of the information. Data on the study design and outcomes were collected for each selected study. The dose ratio from epoetin alfa to darbepoetin alfa was calculated for each study, and the results were reported stratified by study characteristics. To control for differences in study design and characteristics that could explain the variability in the relative dosages of the two agents across studies, multivariate regression analysis was conducted. Based on these results, a dose conversion ratio for Canada was estimated.

Results: A total of 21 studies involving 16?378 patients exposed to epoetin alfa or darbepoetin alfa in CKD were identified. Univariate analysis of the dose ratios indicated a mean dose ratio of 217:1 (IU of epoetin alfa:µg of darbepoetin alfa). Results from the multivariate analysis demonstrated that the study design (i.e., switch study versus straight comparison studies) and geographical coverage (i.e., United States) affected the results. Based on the multivariate analysis, the dose conversion ratio between epoetin alfa and darbepoetin alfa for Canada was 169:1.

Conclusions: Despite limitations associated with switching studies and the limited total number of studies available, this systematic review based on aggregated results provides further evidence to the clinical community that the dose conversion ratio for epoetin alfa:darbepoetin alfa in CKD patients in Canada is approximately 169:1. At that ratio, treatment with epoetin alfa is 11–18% cheaper than treatment with darbepoetin alfa in Canada.     

慢性肾脏病非透析患者服药依从性现状及其影响因素研究

目的　了解慢性肾脏病（CKD）非透析患者服药依从性现状,探讨分析其服药依从性的影响因素。方法　采用便利抽样法,选取2020年1月至2021年12月西安市中心医院收治的CKD非透析患者为研究对象。应用一般资料调查表、服药依从性量表、服药信念量表、多维领悟社会支持量表及医院焦虑抑郁量表对患者进行横断面问卷调查,采用单因素分析及多因素logistic回归分析CKD非透析患者服药依从性的影响因素。结果　共纳入342例CKD非透析患者,男性185例,女性157例,年龄（63.6±24.7）岁,服药依从性评分为（6.02±1.54）分,低依从性患者141例（41.23%）、中/高依从性患者201例（58.77%）。多因素分析显示,服药种数、CKD分期、药物不良反应经历、服药信念、社会支持、焦虑及抑郁是CKD非透析患者服药依从性的影响因素（均P<0.05）。结论　CKD非透析患者服药依从性现状不理想,医务人员应根据影响依从性的关键因素有针对性地采取干预措施,以提高其服药依从性、延缓CKD进展。     

Preference for monthly darbepoetin alfa dosing in patients with chronic kidney disease not receiving dialysis

ABSTRACT

Objective: To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis.

Methods: AMPS (Aranesp Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged ≥18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10–12?g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once- every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous onceweekly Epoetin alfa.

Results: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1]?g/dL at week 29 versus 11.4 [0.7]?g/dL at baseline). QM darbepoetin alfa was well tolerated.

Conclusion: These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.     

The effect of hospitalization on potentially inappropriate medication use in older adults with chronic kidney disease

Objectives: Potentially inappropriate medication (PIM) use is associated with increased morbidity and mortality in chronic kidney disease (CKD). However, there is a paucity of data on how hospitalization affects PIM use in older adults with CKD. Therefore, we aimed to measure the impact of hospitalization on PIM use in older CKD patients, and identify factors predicting PIM use.

Methods: A retrospective cohort study was conducted in older adults (≥65 years) with CKD admitted to an Australian tertiary care hospital over a 6 month period. PIM use was measured, upon admission and at discharge, using the Medication Appropriateness Index (MAI) and Beers criteria (2015 version) for medications recommended to be avoided in older adults and under certain conditions.

Results: The median age of the 204 patients was 83 years (interquartile range (IQR): 76–87 years) and most were men (61%). Overall, the level of PIM use (MAI) decreased from admission to discharge (median [IQR]: 6 [3–12] to 5 [2–9]; p?<?.01]). More than half of the participants (55%) had at least one PIM per Beers criterion on admission, which was reduced by discharge (48%; p?<?.01). People admitted with a higher number of medications (β 0.72, 95% CI 0.56–0.88) and lower eGFR values (β???0.11, 95% CI ?0.18 to ?0.04) had higher MAI scores after adjusting for age, sex and Charlson’s comorbidity index.

Conclusions: PIMs were commonly used in older CKD patients. Hospitalization was associated with a reduction in PIM use, but there was considerable scope for improvement in these susceptible individuals.     

Alprazolam-reinforced medication use in outpatients with anxiety

The reinforcing effects of alprazolam were investigated in 14 patients who had generalized anxiety or panic disorder, but were not current users/abusers of other psychoactive substances. Using a double-blind outpatient choice procedure, color-coded alprazolam (0.5 mg) and placebo capsules were provided to patients for use ‘as needed’ in the treatment of anxiety symptoms. Comparisons of alprazolam and placebo during a 2 week sampling period in which placebo and alprazolam were available sequentially revealed no significant differences on measures of medication usage or anxiety levels, although alprazolam did increase subjective ratings of drug effects/side effects. During a 4 week choice period, alprazolam was strongly preferred over placebo in 11 out of 14 patients indicating that alprazolam functioned as a reinforcer. Medication usage ranged from zero to 4.0 mg alprazolam in a day. Variations in daily medication-use were positively correlated with anxiety level fluctuations for a majority of patients. For a majority of patients, the results indicate that alprazolam functioned as a reinforcer without accompanying signs of abuse or addiction.     

Evaluation of the impact of pharmaceutical care service on hospitalized patients with chronic kidney disease in Jordan

Objectives The primary goal of the present study was to implement and evaluate the impact of pharmaceutical care service for hospitalized chronic kidney disease (CKD) patients in Jordan. Setting Nephrology wards of one of the largest general hospitals in Jordan. Methods All patients who were previously diagnosed with CKD by their physician were eligible for inclusion in the study. Recruited patients were fully assessed for treatment related problems (TRPs) by a clinical pharmacist. Pharmaceutical care service was assessed through a systematic, prospective before–after design. Chi Square test was used to investigate association between categorical variables. P value <0.05 was considered to be statistically significant. Main outcome measures Study outcomes included: Process outcomes (prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs), General clinical outcomes (Therapeutic outcomes of TRPs) and CKD specific clinical outcomes (Change from baseline in the number of patients receiving appropriate progression modifying therapy and appropriate management of complications). Results 130 patients were included in the study. The average number of the identified TRPs was 5.31. Eighty-six percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category. Seventeen percent of all TRPs were resolved, 5.5 % were improved, and 37.4 % were prevented through the clinical pharmacist interventions. Conclusions The current study indicated that hospitalized patients with CKD suffer from multiple TRPs mostly related to efficacy of medications and patients monitoring. Clinical pharmacists substantially contributed towards the care of hospitalized CKD patients through optimizing progression modifying therapies, medications safety and management of CKD complications. Based on this study it is strongly recommended to implement pharmaceutical care services for hospitalized CKD patients.     

慢性肾脏病对患者氧化应激程度的影响及可能意义

目的 探讨慢性肾脏病患者氧化应激的变化以及可能意义.方法 选择我院肾内科住院的慢性肾脏病患者73例,以同期我院体检中心47例体检健康者为对照组.收集受试者血和尿标本,分别用硫代巴比妥酸法和黄嘌呤氧化酶法测定脂质过氧化产物丙二醛和超氧化物歧化酶(SOD)的水平;同时收集患者临床资料,分析慢性肾脏病患者氧化应激程度的变化,同时探讨慢性肾脏病不同分期对氧化应激程度的影响.结果 慢性肾脏病组血丙二醛明显高于对照组[(16.7±20.3)μmol/L比(5.9±1.2)μmol/L,P＜0.05],尿丙二醛和对照组差异无统计学意义[(3.7±3.2)μmol/L比(5.2±4.5)μmol/L,P＞0.05].慢性肾脏病组血SOD和尿SOD活性分别为(37 300±18 200)U/L、(16 200±5600)U/L明显低于对照组[分别为(44 000±9400)U/L、(24 600±7200)U/L,均P＜0.05].结论 慢性肾脏病患者氧化应激程度明显增高,氧化应激随着肾功能的恶化而进一步加重.

Abstract：

Objective To study the oxidative stress in patients with chronic kidney disease (CKD) and its potential significance. Methods Seventy-three in-patients with CKD at the division of nephrology and 47 health controls were enrolled in this study between 2007 and 2010. The blood and urine samples were collected to detect malonaldehyde (MDA) and the activity of superoxide dismutase (SOD). Meanwhile the clinical datum was analyzed to evaluate the impact of CKD on oxidative stress. Results Serum MDA dramatically increased in patients with CKD than that in controls [( 16.7 ± 20.3 ) μmol/L vs ( 5.9 ± 1.2 ) μmol/L,P ＜ 0.05], while SOD of serum and urine in CKD group decreased significantly compared with controls [(37 300 ± 18 200) U/L vs (44 000 ±9 400) U/L, ( 16200 ± 5 600) U/L vs ( 24 600 ± 7 200) U/L, P ＜ 0.05].. Conclusion Oxidative stress is enhanced in patients CKD and it aggravates with the deterioration of kidney function.     

Pharmacist impact on posttraumatic seizure prophylaxis in patients with head injury

Phenytoin is the most commonly administered antiepileptic agent for the prevention of early (< or = 7 days) posttraumatic seizures. Use of the agent, however, requires strict monitoring due to its narrow target range and nonlinear pharmacokinetics. The impact of a clinical pharmacist participating in the care of patients with head injury on posttraumatic seizure prophylaxis with regard to phenytoin dosing and monitoring, cost avoidance, and patient outcome, was measured retrospectively. Parameters from time periods before (BP) and after (AP) a clinical pharmacist participated in patient care were compared. The average number of days that phenytoin was given was 13.4 (BP) and 7.6 (AP), and the duration of phenytoin prophylaxis was 7 days or less in 35% and 65% of patients, respectively. The average number of phenytoin levels drawn from each patient was 10.3 (BP) and 3.4 (AP). Seizures occurred in 4.7% (BP) and 1.5% (AP) of patients. A cost savings of approximately $28,000 was observed for the AP group. A clinical pharmacist reduced the use of posttraumatic seizure prophylaxis and associated costs without jeopardizing patient outcomes.     

Acute kidney injury after non-cardiovascular surgery: risk factors and impact on development of chronic kidney disease and long-term mortality

Objective: To identify factors associated with acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) in a non-cardiac/non-vascular surgery setting.

Methods: This study examined the Veterans Affairs Surgical Quality database for surgical entries between 2000–2014. Demographics, comorbidities, laboratory findings and hospital outcomes were assessed. The primary end-point was the occurrence of AKI, defined as an increase of ≥0.3?mg/dL, 48?h post-operatively. Major adverse cardiac event (MACE) was defined as the composite first occurrence of myocardial infarction, cardiac arrest, and death in 30 days (secondary end-point) and was compared between two groups. Rates of progression to CKD in 1 year and long-term survival were examined.

Main outcome measures: Occurrence of AKI 48?h post-operatively.

Results: AKI was documented in 8.5% of patients. Age, diabetes, and chronic obstructive pulmonary disease, chronic kidney disease, platelet count, serum albumin level, and duration of surgery were identified as independent predictors of AKI. In total, 6.4% patients developed MACE, which was more frequent in patients with AKI (p?Conclusion: Development of AKI is associated with increased odds of various post-operative complications and long-term renal insufficiency and mortality.     

Environmental and individual predictors of medication adherence among elderly patients with hypertension and chronic kidney disease: A geospatial approach

BackgroundFew studies have examined how adherence to antihypertensive medications varies across different regions or how neighborhood-level factors were related to individuals’ medication-taking behaviors in patients.ObjectiveTo explore local variation in medication adherence and examine environmental and individual influences on adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) among elderly hypertensive patients with chronic kidney disease (CKD) in the United States.MethodsThe Medicare 5% sample claim data (2006-2013), American Community Survey 5-Year Data (2005-2009) and the Health Resources and Services Administration Primary Care Service Area data (2007). The primary outcome was medication adherence, measured by Proportion of Days Covered (PDC). Geographically weighted regression (GWR) and linear mixed-effects models were used to investigate the relationship between environmental factors, individual risk factors and medication adherence.ResultsA total of 70,201 hypertensive CKD patients residing in 2,981 counties of the US were selected. Significant spatial autocorrelation was observed in ACEIs/ARBs PDC. The West North Central and New England regions demonstrated higher adherence compared to the East South Central and West South Central regions. Residing in Medically Underserved Areas, counties with high deprivation scores, and not receiving Part D Low-income Subsidy were associated with poor medication adherence.ConclusionsMedication adherence is geographically differentiated across the US. Environmental and individual factors identified may be helpful in the design of local interventions focused on improving patient outcomes from a population perspective.