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Byline: Amy Barton Pai, PharmD, BCPS, FASN (University of New Mexico Health Sciences Center, College of Pharmacy and School of Medicine, Albuquerque, New Mexico, abpai@salud.unm.edu); Todd A. Conner, PharmD (University [...]

Patients with chronic kidney disease (CKD) are at high risk for clinically significant medication therapy problems (MTPs) due primarily to the complex pharmacotherapy prescribed by numerous providers, and the significant changes in pharmacokinetic and pharmacodynamic properties of many medications due to their kidney disease. While MTPs are well recognized, pharmacists are not routinely involved in the health care teams that provide care for patients with CKD. The Advancing American Kidney Health initiative was announced in July 2019 and is poised to shift models of care in nephrology toward value‐based payment. This represents an opportunity for pharmacists to integrate into teams to improve quality of care and outcomes for patients with CKD. Pharmacists should engage in medication reconciliation, transitions of care, and medication‐focused kidney disease education programs within a comprehensive medication management (CMM) framework to optimize pharmacotherapy outcomes. To implement these services, pharmacists need to utilize certified pharmacy technicians, telehealth, interprofessional skills, and other tools in innovative ways. Current models of successful practice from Canada can serve as a template for United States‐based nephrology pharmacy practice. In this opinion paper, we characterize the current state of nephrology practice and identify significant opportunities for advancement. We propose metrics to evaluate pharmacy services and a framework for key stakeholder engagement which will be critical to advance the profession of pharmacy within nephrology. The Advancing American Kidney Health initiative offers a distinct opportunity to demonstrate the value of CMM provided by pharmacists in the nephrology arena to optimize patient care. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the impact of hemodialysis on the concentrations of sodium and potassium in the blood when a 25 g dose of sodium thiosulfate injection is infused over 60 minutes in combination with hemodialysis. Methods: Sodium thiosulfate (25 g) was prepared by diluting 100 mL of 250 mg/mL Sodium Thiosulfate Injection with 800 mL of 5% dextrose. This was added to the circulating blood surrogate solution at a rate of 15 mL/minute using an infusion pump of an in vitro model of dialysis machine. Serial samples were collected before the administration of the sodium thiosulfate solution, after 15 minutes, 30 minutes, and 60 minutes of infusion from pre-and post-dialyzer ports in both the dialysate circuit and the extracorporeal circuit. Findings: The concentration of sodium thiosulfate in pre-dialyzer and post-dialyzer samples of the circulating blood surrogate solution peaked at 30 minutes and 15 minutes, respectively and then remained relatively unchanged during the remainder of the infusion. Mean sodium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 103.2 ± 12.2, 114.2 ± 18.8, 117.2 ± 7.5, 93.5 ± 5.9 at 0, 15, 30, and 60 minutes, respectively (p = 0.248). Mean potassium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 1.4 ± 0.3, 1.6 ± 0.3, 1.5 ± 0.1, 1.2 ± 0.1 at 0, 15, 30, and 60 minutes, respectively (p = 0.365). Sodium and potassium concentrations in dialysate increased marginally after exposure to the dialyzer. Discussion: Our study demonstrates that neither potassium nor sodium accumulated in circulating blood surrogate solution when a dose of sodium thiosulfate was infused in conjunction with hemodialysis. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause community-acquired acute kidney injury, especially in high-risk populations. Both the U.S. Food and Drug Administration (FDA) medication guide and over-the-counter labeling vaguely describe kidney risks of NSAIDs and do not provide information for patients to evaluate their risk for kidney problems. The purpose of this study was to use a mobile application to evaluate the impact of patient choice of media delivering NSAID avoidance education on patient knowledge about kidney risks associated with NSAIDs. Prospective cohort study. The mobile application was used to deliver either a redesigned FDA medication guide or a video focused on NSAID risks (selected by the patient), followed by patient knowledge questions (PKQs) and a kidney risk assessment. One hundred fifty adult primary care patients in southeast Michigan. The primary outcome was the score on 5 NSAID PKQs between the media selected. Secondary outcomes included characterization of media choice among different demographic and NSAID kidney risk groups. The relationship between kidney risk assessment and self-reported NSAID avoidance behavior also was evaluated. The majority of participants (72.7%) chose to review print material. Those that chose print had significantly higher PKQ scores (5 total points) compared with participants who selected the video: mean scores 4.2 ± 0.9 with print and 3.8 ± 1.0 with video (P = 0.034). Older patients (>65 years) had significantly lower PKQ scores compared with other age groups. Forty-four percent of individuals (n = 66) reported current NSAID use, and 65% stated that they would avoid NSAIDs after the selected education material. Scores for questions related to NSAID kidney risk knowledge were higher among participants who chose print compared with video education material. Education regarding NSAID kidney risks encouraged patients to limit their use. Targeted education may be beneficial in high-risk (e.g., older) patients and should be further studied. [ABSTRACT FROM AUTHOR]

Tunneled central venous catheters (TCVCs) are used for dialysis access in 82% of new hemodialysis patients and are rapidly colonized with Gram-positive organism (e.g. Staphylococcus aureus) biofilm, a source of recurrent infections and chronic inflammation. Lipoteichoic acid (LTA), a cell wall ribitol polymer from Gram-positive organisms, mediates inflammation through the Toll-like receptor 2 (TLR2). The effect of LTA on lung endothelial permeability is not known. We tested the hypothesis that LTA from Staphylococcus aureus induces alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM) that result from activation of TLR2 and are mediated by reactive oxygen/nitrogen species (RONS). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin, the activation of the TLR2 pathway was assessed by Western blot, and the generation of RONS was measured by the fluorescence of oxidized dihydroethidium and a dichlorofluorescein derivative. Treatment with LTA or the TLR2 agonist Pam(3)CSK(4) induced significant increases in albumin permeability, IκBα phosphorylation, IRAK1 degradation, RONS generation, and endothelial nitric oxide synthase (eNOS) activation (as measured by the p-eNOSser1177: p-eNOSthr495 ratio). The effects on permeability and RONS were effectively prevented by co-administration of the superoxide scavenger Tiron, the peroxynitrite scavenger Urate, or the eNOS inhibitor L-NAME and these effects as well as eNOS activation were reduced or prevented by pretreatment with an IRAK1/4 inhibitor. The results indicate that the activation of TLR2 and the generation of ROS/RNS mediates LTA-induced barrier dysfunction in PMEM. [ABSTRACT FROM AUTHOR]

Intravenous iron therapy is pivotal in the treatment of anemia of chronic kidney disease to optimize the response of hemoglobin to erythropoiesis-stimulating agents. Intravenous iron use in patients with chronic kidney disease is on the rise. Recent clinical trial data prompting safety concerns regarding the use of erythropoiesis-stimulating agents has stimulated new US Food and Drug Administration label changes and restrictions for these agents, and has encouraged more aggressive use of intravenous iron. The currently available intravenous iron products differ with regard to the stability of the iron-carbohydrate complex and potential to induce hypersensitivity reactions. Ferumoxytol is a newer large molecular weight intravenous iron formulation that is a colloidal iron oxide nanoparticle suspension coated with polyglucose sorbitol carboxymethyl ether. Ferumoxytol has robust iron-carbohydrate complex stability with minimal dissociation or appearance of free iron in the serum, allowing the drug to be given in relatively large doses with a rapid rate of administration. Clinical trials have demonstrated the superior efficacy of ferumoxytol versus oral iron with minimal adverse effects. However, recent postmarketing data have demonstrated a risk of hypersensitivity that has prompted new changes to the product information mandated by the Food and Drug Administration. Additionally, the long-term safety of this agent has not been evaluated, and its place in the treatment of anemia of chronic kidney disease has not been fully elucidated. [ABSTRACT FROM AUTHOR]

Discusses research on the use of antibiotic lock (AL) solutions in hemodialysis catheter-related bloodstream infections. Information on the catheter salvage approach; Aim of prevention strategies that use AL; Efficacy of an AL with gentamicin and heparin.

Presents information on the use of iron supplements in the treatment of anemia of chronic kidney disease. List of intravenous iron formulations; Potential causes of the high incidence of cardiovascular mortality in hemodialysis patients; Factors that have been implicated in generation of oxidative stress in end-stage renal disease.

Objectives: Patients on hemodialysis have complicated medication regimens requiring the ability to accurately interpret medication information. Literacy and numeracy skills have been shown to differ by the types of materials provided to patients. The aims of this study were to determine prescription and over-the-counter medication label understanding and to assess the prevalence of low health literacy regarding medication labeling among in-center hemodialysis patients.Design, Setting and Participants: The Medication Literacy and Numeracy in Dialysis (MedLitD) tool is an assessment of a person's ability to read and understand medication labels. A comparison with the Rapid Estimate of Adult Literacy in Medicine Short Form (REALM-SF), an established literacy tool, was conducted to determine if there were differences in the literacy results from the 2 tools that could be leveraged to target education initiatives for this specialized population.Results: A total of 110 patients receiving hemodialysis from 3 dialysis facilities in the Capital Region of upstate New York were enrolled in the study. Most patients (77%) achieved a maximum REALM-SF score, indicating a high level of literacy proficiency; however, their MedLitD scores varied. Patients who were 65 years and older had lower scores on the MedLitD tool compared with younger patients. Gender, education, and the number of medications did not influence the MedLitD scores. Only 16% of all participants correctly answered the question asking for an indication of the phosphate binder (PB), although the most patients were currently taking PBs.Conclusion: A continuum of medication literacy levels exists among patients on hemodialysis. Appropriate evaluation of medication literacy should be done to better inform individualized education and counseling. [ABSTRACT FROM AUTHOR]

Discusses the effects of administrating intravenous iron to hemodialysis patients who are at risk with bacteremia. Risk factors for vascular access bacteremia in hemodialysis patients; Iron and mechanisms of bacterial pathogenesis; Relationship between iron and bacteremia in end-stage renal disease patients.

Focuses on the use of warfarin for the prevention of vascular access thrombosis in hemodialysis patients. Annual hospital admissions which result from vascular access related complications in hemodialysis patients; Pathogenesis of vascular access thrombosis; Clinical trials of warfarin for prevention of access thrombosis.

The authors discuss the potential of pharmacy technicians within dialysis facilities in growing and sustaining medication management services provided by pharmacists to dialysis patients. Topics mentioned include potential medication-related problems (MRPs) in dialysis-dependent patients, lack of patient knowledge and poor health literacy, and the goal of ESRD Seamless Care Organizations to reduce the frequency of MRPs through medication management.

Introduction: The hypoxia-inducible factor prolyl hydroxylase (HIF-PH) pathway is responsible for regulating the biosynthesis of erythropoietin (EPO) and maintaining iron homeostasis. Investigational drugs that target the HIF-PH pathway are promising alternatives for treating anemia in Chronic Kidney Disease (CKD)., Areas Covered: This review summarizes recent advances focused on the clinical development of HIF-PH inhibitors (HIF-PHIs) as potentially novel therapies in the treatment of anemia in CKD based on publications available on PubMed and restricted Google searches. We provide a comparison between HIF-PHIs regarding their pharmacokinetics, dosing regimens and safety concerns, structure-activity relationships, and alterations in key laboratory parameters observed in animal models and clinical trials., Expert Opinion: HIF-PHIs may be advantageous in some aspects compared to the conventional erythropoiesis-stimulating agents (ESAs). While ESAs could increase the risk of cardiovascular events due to rapid rises in ESA blood levels, HIF-PHIs have been reported to maintain EPO concentrations at levels that are closer to the normal physiological ranges. Although HIF-PHIs have been demonstrated to be relatively safe and effective in clinical trials, long-term safety data are needed in order to establish whether these therapeutic agents will lead to a major paradigm change in the treatment of anemia of CKD.

Competing Interests: L. Dickinson reports other from National Research Network, American Academy of Family Physicians during the conduct of the study; and grants from National Institute of Diabetes and Digestive and Kidney Diseases outside the submitted work. J. Vassalotti reports other from Janssen and other from Renalytix AI, outside the submitted work. All remaining authors have nothing to disclose.