Uremic Toxins and Organ Failure [1st ed.] 9789811577925, 9789811577932

Table of contents :
Front Matter ....Pages i-viii
Overview of Uremic Toxins (Toshimitsu Niwa)....Pages 1-15
Review: Uremic Toxins and Gut Microbiome (Takehiro Suzuki, Takaaki Abe)....Pages 17-39
Gut Microbiota and Systemic Uremic Solute Accumulation (Eikan Mishima)....Pages 41-51
Uremic Toxin-Related Systemic Disorders (Suguru Yamamoto)....Pages 53-67
Uremic Toxins and Cardiovascular Disease (Toyoaki Murohara)....Pages 69-81
Indoxyl Sulfate and Arteriosclerosis (Toshiaki Nakano)....Pages 83-93
Uremic Toxicity and Bone in CKD (Yoshiko Iwasaki, Hideyuki Yamato, Masafumi Fukagawa)....Pages 95-114
D-serine as a Novel Uremic Toxin (Haruki Ouchi, Yosuke Hirakawa, Reiko Inagi)....Pages 115-129
Uremic Solutes and Sarcopenia (Hiroshi Watanabe, Hiromasa Kato, Yuki Enoki, Hitoshi Maeda, Toru Maruyama)....Pages 131-147
Toxico-Pathological Role of Hepatic Sulfotransferase (SULT) 1A1 in Acute Kidney Injuries (Hideyuki Saito)....Pages 149-166
Accumulation of Uremic Toxins in Systemic Organs and the Effect of AST-120 (Emiko Sato)....Pages 167-180

Citation preview

Uremic Toxins and Organ Failure Hideyuki Saito Takaaki Abe Editors

123

Uremic Toxins and Organ Failure

Hideyuki Saito  •  Takaaki Abe Editors

Uremic Toxins and Organ Failure

Editors Hideyuki Saito Department of Pharmacy Kumamoto University Hospital Kumamoto University Kumamoto Japan Department of Clinical Pharmaceutical Sciences

Takaaki Abe Division of Nephrology, Endocrinology, and Vascular Medicine Tohoku University Graduate School of Medicine Sendai Japan

Graduate School of Life Sciences, Kumamoto University Kumamoto Japan

ISBN 978-981-15-7792-5    ISBN 978-981-15-7793-2 (eBook) https://doi.org/10.1007/978-981-15-7793-2 © Springer Nature Singapore Pte Ltd. 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Contents

1 Overview of Uremic Toxins ����������������������������������������������������������������������   1 Toshimitsu Niwa 2 Review: Uremic Toxins and Gut Microbiome ����������������������������������������  17 Takehiro Suzuki and Takaaki Abe 3 Gut Microbiota and Systemic Uremic Solute Accumulation ����������������  41 Eikan Mishima 4 Uremic Toxin-Related Systemic Disorders����������������������������������������������  53 Suguru Yamamoto 5 Uremic Toxins and Cardiovascular Disease��������������������������������������������  69 Toyoaki Murohara 6 Indoxyl Sulfate and Arteriosclerosis��������������������������������������������������������  83 Toshiaki Nakano 7 Uremic Toxicity and Bone in CKD ����������������������������������������������������������  95 Yoshiko Iwasaki, Hideyuki Yamato, and Masafumi Fukagawa 8 D-serine as a Novel Uremic Toxin������������������������������������������������������������ 115 Haruki Ouchi, Yosuke Hirakawa, and Reiko Inagi 9 Uremic Solutes and Sarcopenia���������������������������������������������������������������� 131 Hiroshi Watanabe, Hiromasa Kato, Yuki Enoki, Hitoshi Maeda, and Toru Maruyama 10 Toxico-Pathological Role of Hepatic Sulfotransferase (SULT) 1A1 in Acute Kidney Injuries������������������������������������������������������������������� 149 Hideyuki Saito 11 Accumulation of Uremic Toxins in Systemic Organs and the Effect of AST-120�������������������������������������������������������������������������� 167 Emiko Sato

v

Introduction

During the pathogenic progress of acute kidney injury (AKI) and chronic kidney disease (CKD), the ability to remove many potent toxic metabolites from blood to urine is declined, thereby leading to various organ disorders and/or failures. Uremic-­ retained solutes are called uremic toxins if those affect normal organ functions. It is important to characterize which uremic retained solutes are indeed “uremic toxins” and to elucidate the pathological mechanisms involved in their toxic impacts on the kidney and other organs. Exploration of mechanisms of uremic toxin-related organ damages would confirm the relevance of clinical symptoms to the toxins, the possibility of discovering pathophysiological linkage between developed renal diseases and functional loss of non-renal organs as well as the diagnostics for clinical use and the identification of organ failure-specific biomarkers. In special patient populations including elderly, those giving long-term medication, pregnant women, patients with liver or cardiovascular disease, or transplantation, the control of circulating uremic toxin levels would become an important therapeutic concern. The term “uremic syndrome” represents the clinical situation of systemic accumulation of uremic toxins which are efficiently eliminated into the urine under healthy conditions. Despite that clinical symptoms associated with uremic accumulation have been known for decades, the origin, chemical entities, and composition of the retained uremic solutes responsible for these diseases have not been well identified. In kidney diseases, two possible types of uremic toxins having an impact on the severity of symptoms have been considered: the toxins with declined glomerular filtration or renal tubular functions, and toxins related to the metabolic processes of various cell types and organs damaging the non-renal organs. To date, a variety of sophisticated techniques have been utilized in investigations for the identification, characterization, analytical quantification, and examinations of the toxicological and pharmacological aspects of uremic toxins. Based on the molecular features of uremic toxins, many problems regarding the evaluation of uremic solutes and their potential roles in the diagnostic evaluation have been investigated. The expected outcome of these studies should be discovery/development of effective treatments for preventing toxic effects of uremic toxins or amelioration of uremic toxin accumulation at various stages of AKI and CKD.  In this book, the state-of-art reviews including an overview of uremic toxins, gut–kidney axis,

vii

viii

Introduction

uremic toxins-related several organ failures, and preventive strategies for reduction of uremic toxins are summarized. Kumamoto, Japan

Sendai, Japan

Hideyuki Saito Takaaki Abe

1

Overview of Uremic Toxins Toshimitsu Niwa

Abstract

This chapter focuses on the overview of uremic toxins. More than 100 uremic toxins have been reported to be retained in uremic serum. Uremic toxins include small water-soluble compounds (molecular weight