Advanced Clinical Pharmacy – Research, Development and Practical Applications 1 Rhiannon Braund Editor Renal Medicine and Clinical Pharmacy Advanced Clinical Pharmacy - Research, Development and Practical Applications Volume 1 Series Editor Rhiannon Braund, University of Otago, Dunedin, New Zealand This exciting new book series Advanced Clinical Pharmacy incorporates new areas of research and development with practical approaches and is designed to aid pharmacists up-skill in various new and traditional areas of practice that are applicable, but not limited to, hospital-based care, as well as incorporating the more advanced aspects of community-based care. Advanced Clinical Pharmacy will incorporate titles that help intermediate level pharmacists see what further areas of practice need to be incorporated in to their skill set, as well as provide guidance on areas of expertise that they may wish to focus on for more advanced practice in the future. It will also provide more advanced pharmacists with a tool for ensuring they are current and up-to-date in a wider range of topics, as well as in their chosen area of expertise. Additionally, it may provide newly registered pharmacists with guidance on what areas of practice they may aspire to work in. The series will provide more comprehensive information that is also more focused than is typically found in traditional clinical pharmacy text books (which cover all topics in a single volume and typically cover a topic in one or two chapters). It will allow pharmacists to select topics that are more applicable to their individual areas of work, as well as areas that in the future they may wish to work in. Each volume will provide a summary of the main theory that underpins the topic, but will then move on to advanced information including areas of current research, clinical applications, case studies, practical tips, and common pitfalls. It will also look at future directions and also, where applicable, hints for the independent practitioner – in preparation for the advancement of pharmacists as more independent health professionals. Titles in the series can be monographs (up to 3 authors) or edited volumes, ranging from 200–500 pages per volume. Each title will be published as ebook as well as in hard bound print format. This series will be of interest to a wide readership, ranging from intermediate level pharmacists, with experience of 3 to 5 years post-registration (for a bachelor’s degree) or experience of 2 to 3 years (for a PharmD), through to more advanced/ senior clinical pharmacists. It is hoped that the information would also be of interest to pharmacists working in community-based care, who wish to increase their knowledge and skill, as well as hospital-based pharmacists. The series may also be useful as educational tools for the teaching of pharmacists involved in both formal post-graduate education as well as more ad hoc workplace based programmes – however, different titles in the series may be more suitable for this than others. Unique features • Offers readers the ability to select the topics that are of interest to them and focus on their area of work/expertise • Provides the salient points of the background theory but then quickly moves on to more advanced knowledge that contains both current research as well as prac- tical information in the context of cases (but not limited to case scenarios) More information about this series at http://www.springer.com/series/15660 Rhiannon Braund Editor Renal Medicine and Clinical Pharmacy Editor Rhiannon Braund University of Otago Dunedin, New Zealand ISSN 2524-5325 ISSN 2524-5333 (electronic) Advanced Clinical Pharmacy - Research, Development and Practical Applications ISBN 978-3-030-37654-3 ISBN 978-3-030-37655-0 (eBook) https://doi.org/10.1007/978-3-030-37655-0 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG. The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland To Emily May White (2002–2017), who gave the gift of life. Preface While many young pharmacists emerge into practice with a substantive knowledge base, the evolution of clinical practice coupled with the required additional special- ized knowledge that comes from clinical specialties can make it difficult to evolve as a practitioner. This knowledge can be hard to gather from senior clinicians and from specialized medical texts and usually requires a pharmacist to have worked in the specialty for a considerable period of time. These texts facilitate the uptake of this knowledge, by providing the background details of key concepts, in an easy to understand manner and in a way that is targeted specifically to pharmacists. This series of books have been designed to allow new practitioners, or those moving into new clinical areas, a refresher of the core pharmaceutical concepts, as well as moving on to the rationale optimisation of pharmacotherapy, and finishing with advanced clinical practice. Included are pearls of wisdom, from other practitio- ners, as well as common pitfalls. This provides a solid platform to then develop further expertise. In these books, international experts with specialist clinical knowledge have dis- tilled the core knowledge of each clinical area, providing real-world insights to create a book that will help guide junior pharmacists to become the specialist phar- macists of the future. Dunedin, New Zealand Rhiannon Braund vii Contents 1 Introduction to Renal Pharmacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Carolyn Coulter 2 How Kidney Function Affects Drug Pharmacokinetics . . . . . . . . . . . . 5 Carolyn Coulter 3 Acute Kidney Injury: Pre-renal, Intra-renal and Post-renal . . . . . . . . 23 Christine Sluman, Pooja Mehta Gudka, and Kathryn McCormick 4 Chronic Kidney Disease and End Stage Renal Disease . . . . . . . . . . . . . 45 Dan Martinusen 5 Dialysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Timothy Nguyen, A. Mary Vilay, Neeta Bahal O’Mara, and Rebecca Maxson 6 Drug-Induced Nephrotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Adriano Max Moreira Reis Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 ix Chapter 1 Introduction to Renal Pharmacy Carolyn Coulter Abstract Renal dysfunction is a common reason for requiring pharmacists to adjust their thinking when optimizing a drug dosing regimen. However, many phar- macists find this clinical task quite daunting as there are many factors to consider, such as whether renal clearance alone is affected, if renal metabolism is also affected, if there renal pathology to consider, if this an acute situation or more chronic or even both, and if renal replacement therapy indicated. But if each ques- tion is considered in a logical stepwise manner, then often this process becomes much easier to understand. There may still be unanswered questions at the end of this process, but usually there is a great clarity around these and whether they are going to impact the patient clinically. Keywords Renal pharmacy · Renal dysfunction · Pharmacotherapy · Clinical practice · Nephrology · Pharmacy practice · Adverse drug reactions Renal dysfunction is a common reason for requiring pharmacists to adjust their thinking when optimizing a drug dosing regimen. However, many pharmacists find this clinical task quite daunting as there are many factors to consider, such as whether renal clearance alone is affected, if renal metabolism is also affected, if there renal pathology to consider, if this an acute situation or more chronic or even both, and if renal replacement therapy indicated. But if each question is considered in a logical stepwise manner, then often this process becomes much easier to under- stand. There may still be unanswered questions at the end of this process, but usu- ally there is a great clarity around these and whether they are going to impact the patient clinically. Today there is a greater focus on medicines reconciliation for all patients admit- ted to hospital, and with this comes the perceived need to prescribe all medicines on C. Coulter (*) Timaru Hospital Pharmacy, Timaru, New Zealand e-mail: [email protected] © Springer Nature Switzerland AG 2020 1 R. Braund (ed.), Renal Medicine and Clinical Pharmacy, Advanced Clinical Pharmacy - Research, Development and Practical Applications 1, https://doi.org/10.1007/978-3-030-37655-0_1 2 C. Coulter admission. However, the very key steps in treating patients with renal dysfunction are to initially ask what may have caused, or contributed to, the renal problem and what may further exacerbate it. Then it is appropriate to ask what medicines are required now, and what medicines will be required in the future. Treating patients with renal dysfunction starts by ceasing or with-holding all inappropriate medi- cines, followed by the rational prescribing of medicines while always considering the clinical appropriateness, the optimized dosing regimen, and also the pill burden. For example if you have a patient with an acute kidney injury and you want to review their medicines on admission you firstly need to consider what caused, or contributed, the acute kidney injury. Secondly, what of the regular medicines are currently required, and what can be safely with-held until the kidney injury has resolved. Thirdly, are there any other therapies that should be instigated both for the acute situation and long term for this patient. Chronic kidney disease requires the same analysis, but with a greater focus on the long term requirements. Initially hospital pharmacists may often consider that dose adjustment as per standard renal dosing guidelines is appropriate, these often do not consider the clini- cal complexity that may exist. Guidelines for dose adjustments in renal impairment that are based on reduction in glomerular filtration rate, calculated from creatinine clearance, are an excellent staring point, but then critical thinking must be employed. It is very appropriate to dose adjust a medicine for a chronic condition, but if your patient has severe sepsis then dose adjustment of antibiotics based on creati- nine calculations during an acute kidney injury most likely will lead to treatment failure. Instead if the pharmacist considers the pharmacokinetics, the clinical indi- cation including the need to treat aggressively, then a more appropriate dosing regi- men may be initiated. This dosing regimen may require frequent review with multiple changes over time, especially if the patient improves – or deteriorates fur- ther and requires acute renal replacement. Dose adjustments can also seem complex but these just require consideration of what is the target concentration – is a loading dose required, and for the maintenance dose what proportion is cleared by the kid- neys and by how much this will be affected. Additionally, a pharmacist must watch for therapeutic failure as well as potential toxicity. An appreciation of renal disorders is required for pharmacists who wish to be a valued member of a nephrology team. The kidneys are important for drug dosing as they are one of the most important clearance systems in the body, but they can be affected by processes occurring before the kidneys, such as blood volume and car- diac output, or process after the kidney such as bladder and urological issues. However, there are also many diseases that affect the kidneys – these may be dis- eases just affecting the kidneys such as glomerular nephritis, or they may be sys- temic diseases that also result in renal pathology such as systemic lupus erythematosus. The kidneys can also be affected by xenobiotics in the body, which does include other nephrotoxic medicines. Moreover, the kidneys have a role in acid-base control, electrolyte and water control, they perform some metabolism, as well as regulation of some hormones, and they help control blood pressure. The kidneys can also be affected by congenital structural abnormalities, as well infections, and dysfunction from other organs. If