Pharmacokinetics of Drugs and Dosing in Kidney Disease

A special issue of Pharmacy (ISSN 2226-4787). This special issue belongs to the section "Pharmacy Practice and Practice-Based Research".

Deadline for manuscript submissions: closed (15 April 2020) | Viewed by 36282

Special Issue Editors


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Guest Editor
Division of Clinical Pharmacy, University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, 92093, USA
Interests: chronic kidney disease; acute kidney injury; transplantation; pharmacokinetics; pharmacogenomics

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Guest Editor
Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA 92350, USA
Interests: kidney diseases; antibiotics; pharmacokinetics; pharmacodynamics; renal replacement therapy
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Special Issue Information

Dear Colleagues,

The Pharmacy journal invites academicians, researchers, and clinicians to send abstracts for this Special Issue related to the pharmacokinetics of drugs and drug dosing in acute kidney injury (AKI), chronic kidney disease (CKD), and patients receiving renal replacement therapy (RRT). The abstract is due in July and selected authors will be invited to submit the manuscript.

Chronic kidney disease prevalence is increasing worldwide. Kidney disease influences not only drug elimination (i.e., renal and non-renal) but also pharmacokinetic parameters involved in drug disposition (e.g., absorption, distribution, and transport). Drug dosing in the setting of AKI is complicated by several factors such as pharmacokinetic changes, inaccuracy of renal estimating equations, lack of therapeutic drug monitoring capability for most drugs, and use of extracorporeal renal replacement. Drug dosing is complicated in patients with kidney disease putting them at risk for adverse events and poor patient outcomes. Thus, it is critical to inform clinicians how to optimize the selection and dosing of drugs in patients with kidney disease.

Dr. Linda Awdishu
Dr. Soo Min Jang
Guest Editors

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Keywords

  • Drug dosing considerations
  • Pharmacokinetics
  • Chronic kidney disease
  • Acute kidney injury
  • Dialysis
  • Renal replacement therapy

Published Papers (8 papers)

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Research

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11 pages, 1054 KiB  
Article
The Role of Community Pharmacists in the Detection of Clinically Relevant Drug-Related Problems in Chronic Kidney Disease Patients
by Céline Mongaret, Léa Aubert, Amélie Lestrille, Victorine Albaut, Pierre Kreit, Emmanuelle Herlem, Natacha Noel, Fatouma Touré, François Lallier, Florian Slimano and the MIRPhO Investigators Study
Pharmacy 2020, 8(2), 89; https://doi.org/10.3390/pharmacy8020089 - 22 May 2020
Cited by 5 | Viewed by 3802
Abstract
Community pharmacists (CPs) have traditionally had limited access to patients’ estimated glomerular filtration rate (eGFR) during the medication-dispensing process. The increasing access to shared electronic health records is making eGFR available, but the skills needed to detect and manage clinically relevant drug-related problems [...] Read more.
Community pharmacists (CPs) have traditionally had limited access to patients’ estimated glomerular filtration rate (eGFR) during the medication-dispensing process. The increasing access to shared electronic health records is making eGFR available, but the skills needed to detect and manage clinically relevant drug-related problems (DRPs) are poorly documented. The primary objective of this study was to investigate the role of CPs in the medication-dispensation process for elderly patients with renal impairment. A total of 70 CPs participated in this 6 month study. Community pharmacists asked all patients ≥65 years to bring their laboratory test values for the next medication-dispensing process. Drug-related problem detection rates were compared between CPs (prospective period) and expert pharmacists (retrospectively). The clinical relevance of each DRP was assessed by nephrologists and general practitioners using an appropriate tool. Community pharmacists recruited n = 442 patients with eGFR < 60 mL/min/1.73 m2 and detected n = 99 DRPs, whereas expert pharmacists detected n = 184 DRPs. The most frequently detected DRPs were dosage problems and contraindications. According to assessment by clinicians, CPs and expert pharmacists identified 54.0% and 84.7% of clinically relevant DRPs, respectively. This study suggests a positive impact of the systematic availability of eGFR to CPs on the detection of several DRPs with clinical relevance. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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11 pages, 1171 KiB  
Article
Relationship between 2-Hour Tacrolimus Concentrations and Clinical Outcomes in Long Term Kidney Transplantation
by Jeffrey Yin, Tammy Hsu, Janice S Kerr, Robert Steiner and Linda Awdishu
Pharmacy 2020, 8(2), 60; https://doi.org/10.3390/pharmacy8020060 - 3 Apr 2020
Cited by 3 | Viewed by 2247
Abstract
Background: Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such [...] Read more.
Background: Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. Methods: This is a single center, retrospective study of adult kidney transplant recipients with 2-hour tacrolimus concentrations measured over three years post-transplant. The primary outcome was to determine the difference in serum creatinine (Scr) in those with 2-hour tacrolimus concentrations greater than 20 ng/mL versus those less than or equal to 20 ng/mL. Results: A total of 150 kidney transplant recipients were included. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and 59 ± 23.2 mL/min/1.73 m2, respectively, for the entire cohort. The rate of donor specific antibody formation was 2% and 8% experienced biopsy-proven rejection. The rate of cytomegalovirus viremia was 2% and BK viremia was 13%. There was no significant difference in kidney function over 36 months for the groups specified a priori. Conclusions: Long-term outcomes of maintaining tacrolimus 2-hour concentrations over 20 ng/mL is favorable with minimal opportunistic infections. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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11 pages, 515 KiB  
Article
Prescribing and Safety of Direct-Acting Oral Anticoagulants Compared to Warfarin in Patients with Atrial Fibrillation on Chronic Hemodialysis
by Estella Davis, Dallin Darais, Kevin Fuji, Paige Nekola and Khalid Bashir
Pharmacy 2020, 8(1), 37; https://doi.org/10.3390/pharmacy8010037 - 10 Mar 2020
Cited by 9 | Viewed by 3617
Abstract
ESRD patients receiving hemodialysis (HD) were excluded from landmark trials evaluating direct-acting oral anticoagulants (DOACs) in atrial fibrillation (AF). The objective was to evaluate prescribing and bleeding with DOACs compared to warfarin in AF patients with chronic HD. A retrospective, observational study of [...] Read more.
ESRD patients receiving hemodialysis (HD) were excluded from landmark trials evaluating direct-acting oral anticoagulants (DOACs) in atrial fibrillation (AF). The objective was to evaluate prescribing and bleeding with DOACs compared to warfarin in AF patients with chronic HD. A retrospective, observational study of patients receiving warfarin or DOAC from April 2010-April 2016 from area health system hospitals and Dialysis Clinics, Inc. records. Data was analyzed using descriptive statistics, ANOVA, and chi-square. Ninety-one patients were included with warfarin as the initial OAC in most patients (n = 76) at average dose of 29 mg/week. Fifteen patients were initially prescribed apixaban (n = 12) or dabigatran (n = 3). Most switches in OAC therapy were to apixaban. When the initial OAC was a DOAC, it was not dosed appropriately in five with one bleed, two dosed appropriately had bleeds. When initial warfarin was switched to a DOAC, it was not dosed appropriately in seven with five bleeds. More bleeds occurred with warfarin alone (n = 18) vs. those on warfarin switched to DOAC (n = 5) vs. DOAC alone (n = 3), p = 0.022. All but four patients that bled had HAS-BLED scores three or higher. Warfarin was most often prescribed and associated with a higher incidence of bleeding compared to DOACs in this population of patients at high risk for bleeding. Larger studies should be conducted to analyze the impact of DOAC dose appropriateness on safety and clinical outcomes. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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9 pages, 346 KiB  
Article
Safety and Efficacy of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Renal Impairment
by Soo Min Jang, Khaled Bahjri and Huyentran Tran
Pharmacy 2020, 8(1), 30; https://doi.org/10.3390/pharmacy8010030 - 4 Mar 2020
Cited by 5 | Viewed by 3672
Abstract
Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to [...] Read more.
Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to warfarin. However, safety and efficacy data of DOACs in patients with chronic kidney disease (CKD) are limited. This is a retrospective study to evaluate thromboembolic and bleeding events in patients with AF (with/without CKD) in October 2010 and July 2017. A total of 495 patients were included and only 150 patients had CKD. Our study found that patients with renal impairment on a DOAC do not have a higher incidence of bleeding events. It showed significant increase in thromboembolic events in CKD patients with dabigatran compared to CKD patients with apixaban with odds ratio of 6.58 (95%CI 1.35–32.02, p = 0.02). Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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Review

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19 pages, 2411 KiB  
Review
Cystatin C: A Primer for Pharmacists
by Hilary R. Teaford, Jason N. Barreto, Kathryn J. Vollmer, Andrew D. Rule and Erin F. Barreto
Pharmacy 2020, 8(1), 35; https://doi.org/10.3390/pharmacy8010035 - 9 Mar 2020
Cited by 25 | Viewed by 8733
Abstract
Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring [...] Read more.
Pharmacists are at the forefront of dosing and monitoring medications eliminated by or toxic to the kidney. To evaluate the effectiveness and safety of these medications, accurate measurement of kidney function is paramount. The mainstay of kidney assessment for drug dosing and monitoring is serum creatinine (SCr)-based estimation equations. Yet, SCr has known limitations including its insensitivity to underlying changes in kidney function and the numerous non-kidney factors that are incompletely accounted for in equations to estimate glomerular filtration rate (eGFR). Serum cystatin C (cysC) is a biomarker that can serve as an adjunct or alternative to SCr to evaluate kidney function for drug dosing. Pharmacists must be educated about the strengths and limitations of cysC prior to applying it to medication management. Not all patient populations have been studied and some evaluations demonstrated large variations in the relationship between cysC and GFR. Use of eGFR equations incorporating cysC should be reserved for drug management in scenarios with demonstrated outcomes, including to improve pharmacodynamic target attainment for antibiotics or reduce drug toxicity. This article provides an overview of cysC, discusses evidence around its use in medication dosing and in special populations, and describes practical considerations for application and implementation. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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21 pages, 307 KiB  
Review
Principles of Drug Dosing in Sustained Low Efficiency Dialysis (SLED) and Review of Antimicrobial Dosing Literature
by Paula Brown and Marisa Battistella
Pharmacy 2020, 8(1), 33; https://doi.org/10.3390/pharmacy8010033 - 9 Mar 2020
Cited by 5 | Viewed by 5540
Abstract
The use of sustained low-efficiency dialysis (SLED) as a renal replacement modality has increased in critically ill patients with both acute kidney injury (AKI) and hemodynamic instability. Unfortunately, there is a paucity of data regarding the appropriate dosing of medications for patients undergoing [...] Read more.
The use of sustained low-efficiency dialysis (SLED) as a renal replacement modality has increased in critically ill patients with both acute kidney injury (AKI) and hemodynamic instability. Unfortunately, there is a paucity of data regarding the appropriate dosing of medications for patients undergoing SLED. Dose adjustment in SLED often requires interpretation of pharmacodynamics and pharmacokinetic factors and extrapolation based on dosing recommendations from other modes of renal replacement therapy (RRT). This review summarizes published trials of antimicrobial dose adjustment in SLED and discusses pharmacokinetic considerations specific to medication dosing in SLED. Preliminary recommendation is provided on selection of appropriate dosing for medications where published literature is unavailable. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)

Other

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6 pages, 657 KiB  
Case Report
Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases
by Soo Min Jang, Smitha Anam, Tara Pringle, Paul Lahren and Sergio Infante
Pharmacy 2020, 8(2), 59; https://doi.org/10.3390/pharmacy8020059 - 1 Apr 2020
Cited by 3 | Viewed by 2441
Abstract
A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety [...] Read more.
A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety and efficacy of data in this population. Two hemodialysis patient cases of contrasting responses in parathyroid hormone (PTH) after denosumab administration were observed. Patient 1, a 62-years-old male received denosumab 60 mg at Day 0. His calcium decreased from 8.8 mg/dL to 6.8 mg/dL on Day 30. The PTH level increased from 265 pg/mL to 372 pg/mL after 30 days. Calcium and PTH levels approached normal range after increasing doses of vitamin D/calcium supplements, and calcitriol. Patient 2, a 72-years-old male on hemodialysis also received denosumab 60 mg on Day 0. His baseline calcium and PTH were 9.2 mg/dL and 420 pg/mL, respectively. On Day 30, his calcium level decreased (6.8 mg/dL) but, PTH level drastically increased (>5000 pg/mL). Denosumab commonly causes hypocalcemia and hyperparathyroidism since it inhibits osteoclast activation, reduces calcium release from bone and increases PTH levels as a compensatory mechanism. With a wait-and-watch approach, Patient 2’s levels approached the normal range (calcium 9.6 mg/dL and PTH 274 pg/mL at Day 90). Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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9 pages, 769 KiB  
Opinion
Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy
by Soo Min Jang, Sergio Infante and Amir Abdi Pour
Pharmacy 2020, 8(1), 18; https://doi.org/10.3390/pharmacy8010018 - 7 Feb 2020
Cited by 12 | Viewed by 5097
Abstract
Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ [...] Read more.
Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan. Full article
(This article belongs to the Special Issue Pharmacokinetics of Drugs and Dosing in Kidney Disease)
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