Biomarkers in Kidney Transplantation : Clinical Aspects and Laboratory Determination.

Format:

Book

Author/Creator:

Pattanaik, Smita.

Contributor:

Sharma, Ashish.

Series:

Clinical Aspects and Laboratory Determination Series

Language:

English

Physical Description:

1 online resource (759 pages)

Edition:

1st ed.

Place of Publication:

Chantilly : Elsevier Science & Technology, 2025.

Summary:

Biomarkers in Kidney Transplantation: Clinical Aspects and Laboratory Determination provides a focused study on traditional and emerging biomarkers to predict early rejection of kidney transplants supporting appropriate therapeutic interventions.

Contents:

Front Cover

Biomarkers in Kidney Transplantation: Clinical Aspects and Laboratory Determinations

Copyright Page

Contents

List of contributors

Foreword by Pierre Marquet

Foreword by Vijay Mittal

Foreword by Vinay Sakhuja

Preface

1 Organ transplantation: past, present, and future

Chapter objectives

Abbreviations

1.1 Introduction

1.2 Early experiments

1.3 History of immunosuppression

1.3.1 The first period (1954-1962)

1.3.2 The second period (1963-1980)

1.3.3 The third period (1983-2007)

1.3.4 The fourth period (2007 to present day)

1.4 Kidney transplantations in humans

1.4.1 Past

1.4.2 Present

1.4.3 Future

1.5 Other solid organ transplantations

1.5.1 Liver transplantation

1.5.1.1 Early experiments

1.5.1.2 Present and future

1.5.2 Heart transplantation

1.5.3 Pancrease transplantation

1.5.3.1 History of pancreases transplantation

1.5.4 Lung transplantation

1.5.5 Face transplantation

1.5.6 Uterus transplantation

1.5.6.1 The past

1.5.6.2 The present

1.5.6.3 Future

1.5.7 Bowel transplantation

1.5.8 Limb transplantation

1.5.8.1 Past

1.5.8.2 Present and future

1.6 Xenotransplantation

1.6.1 Past

1.6.2 Present

1.6.3 Future

1.7 Lab-grown organs and organoids for transplantation

1.8 Machine perfusion

1.9 Induction of tolerance

1.10 Future directions

Summary Points

References

2 Trends in kidney transplantation

2.1 Introduction

2.2 Global trends

2.3 Regional trends

2.4 Trends in developing countries

2.5 Trends in deceased donor transplant

2.5.1 Changing donor demographics

2.5.2 Rise in donation after cardiac death (DCD)

2.5.3 Maastricht classification

2.5.4 Uncontrolled donation

2.5.4.1 Donor identification and referral

2.5.4.1.1 Donor referral.

2.5.4.2 Donor transfer

2.5.4.3 Determination of death

2.5.4.4 Preservation

2.5.4.5 Normothermic regional perfusion (NRP)

2.5.4.6 Consent and authorization for donation

2.6 Trends in living donor transplantation

2.6.1 Decrease in living donation

2.7 Trends in newer categories of living donor transplantation

2.7.1 Paired kidney exchange

2.7.2 Desensitization

2.7.2.1 Desensitization modalities

2.8 Trend of immunosuppressive medications over the last decade

2.8.1 Induction immunosuppression

2.8.2 Maintenance immunosuppression

2.9 Future prospects

2.9.1 Robotic-assisted kidney transplantation (RAKT)

2.9.2 Machine perfusion

Summary points

3 Immunobiology in kidney transplantation

3.1 Introduction

3.2 The human immune system

3.2.1 Innate immune system

3.2.2 Adaptive immune system

3.3 Mechanisms of alloantigen recognition

3.3.1 Direct pathway

3.3.2 Indirect pathway

3.3.3 Semidirect antigen presentation

3.4 Human leukocyte antigens

3.5 Other major histocompatibility antigens

3.6 Minor histocompatibility antigens

3.7 Role of T cells in alloimmune response

3.7.1 Two-signal T-cell activation

3.7.2 T-cell activation, proliferation, and differentiation

3.7.3 T-cell homing

3.7.4 T-cell subtypes and their roles

3.8 Role of B cells in alloimmune response

3.8.1 B-cell activation

3.8.2 Secondary lymphoid organs and B-cell activation

3.8.3 Generation of an alloimmune response

3.8.4 Tertiary lymphoid organs

3.9 Role of chemokines and chemokine receptors

3.10 Immune tolerance in renal transplantation

3.11 Translating the immunobiological concepts into clinical practice

3.11.1 Donor-recipient HLA matching

3.11.2 Complement-dependant cytotoxicity (CDC) crossmatch

3.11.2.1 The technique of CDC crossmatch.

3.11.3 Flowcytometry-based crossmatch

3.11.3.1 Flow crossmatch procedure (FCXM)

3.11.4 Solid-phase assays

3.11.4.1 Technique for solid-phase assay

3.11.4.2 Bead-based fluorescent assays such as FlowPRA® (One Lambda, Inc.)

3.11.4.3 Clinical practice implications of the above biomarker assay results

3.11.5 The virtual crossmatch

3.11.6 Challenges of the antigen bead assay for virtual crossmatch

3.11.6.1 Epitopes and eplets

3.11.7 ELISpot assay (ImmunoSpot®)

Future prospects

4 Immunosuppression in kidney transplantation

4.1 Introduction

4.2 Induction immunosuppressive agents

4.2.1 Types of induction agents

4.2.2 OKT 3 (muromunab)

4.2.3 Antilymphocyte antibodies

4.2.3.1 Polyclonal antilymphocyte antibodies

4.2.3.2 Monoclonal antilymphocyte antibodies

4.2.4 IL-2 receptor antagonists

4.2.5 Other biological induction agents

4.2.6 Clinical practice guidelines for use of induction agents

4.2.6.1 Low-risk or standard-risk transplant patients

4.2.6.2 High-risk transplant recipients

4.2.7 Induction of tolerance

4.3 Maintenance immunosuppressive agents

4.3.1 Calcineurin inhibitors

4.3.2 Antiproliferative agents

4.3.2.1 Calcineurin inhibitor conversion

4.3.3 Mammalian target of rapamycin inhibitor(s)

4.3.4 Belatacept and costimulatory blockade

4.4 Evolution of immunosuppressive regimen in renal transplantation

4.4.1 NonCalcineurin inhibitor-based regimens

4.4.2 Steroid withdrawal strategy

4.5 Key developments and landmark clinical trials in transplant immunosuppression

4.5.1 Canadian Multicentre Transplant Study (1983)

4.5.2 Tricontinental Mycophenolate Mofetil Renal Transplantation Study (1995)

4.5.3 CHIB 201 International Study (1997)

4.5.4 Elite Symphony Trial (2007).

4.5.5 The Freedom Study (2008)

4.5.6 Convert Study (2009)

4.5.7 Harmony Trial (2017)

4.5.8 The 3C Study (2018)

4.5.9 BENEFIT and BENEFIT-EXT Trial (2009 to 2017)

4.5.10 Transform Trial (2019)

4.6 Antirejection Immunosuppressive agents

4.6.1 Treatment of T-cell-mediated rejections

4.6.2 Treatment of borderline rejections

4.6.3 Treatment of antibody-mediated rejections

4.6.3.1 Intravenous immunoglobulin (IVIG)

4.6.3.2 Anti-CD20 monoclonal antibody

4.6.3.3 Proteasome inhibitors

4.6.3.4 Complement inhibitors

5 Challenges in the therapeutic drug monitoring of immunosuppressants

5.1 Introduction

5.2 Which immunosuppressants require TDM?

5.3 What is the rationale for TDM of calcineurin and mTOR inhibitors?

5.3.1 Therapeutic windows and narrow therapeutic index

5.3.2 Intra- and interindividual variability of calcineurin and mTOR inhibitor pharmacokinetics

5.3.3 Interindividual variability of calcineurin and mTOR inhibitor pharmacokinetics-the role of pharmacogenomics

5.3.3.1 Underlying pharmacological principles

5.3.3.2 Pharmacogenetics-which role does it play in dose adjustments of immunosuppressants?

5.3.4 What are the contributors to the intraindividual pharmacokinetic variability of calcineurin and mTOR inhibitor?

5.3.4.1 Drug-drug interactions

5.3.4.2 Food-drug interactions

5.3.4.3 Disease-drug interactions

5.3.4.4 Age

5.3.4.5 Sex

5.3.4.6 Chronopharmacokinetics

5.3.4.7 Nonadherence

5.3.4.8 Time after transplantation

5.4 When is TDM of calcineurin and mTOR inhibitors indicated?

5.5 TDM of mycophenolate-what are the advantages?

5.5.1 Is there a relationship between MPA exposure with efficacy and/or toxicity?

5.5.2 Is MPA a narrow therapeutic index drug?.

5.5.3 Has MPA a large inter- and/or intrapatient variability of its pharmacokinetics?

5.5.4 Should mycophenolate dosing be guided by TDM in kidney transplant patients?

5.6 Which pharmacokinetic parameter should be monitored?

5.6.1 Pharmacokinetic parameters used for TDM

5.6.2 Target ranges

5.7 Which is the best matrix for the TDM of Immunosuppressants?

5.7.1 Matrices currently used in routine TDM of immunosuppressants

5.7.2 Dried blood spots

5.7.3 Free fraction

5.7.4 Intracellular concentrations

5.8 Challenges with the measurement of drug concentrations for TDM of immunosuppressants

5.9 TDM-guided dosing of immunosuppressants-population PK, Bayesian forecasting, and machine learning

6 Overview of biomarkers in kidney transplantation

6.1 Introduction

6.2 Biomarkers in renal transplantation

6.3 Biomarkers classified according to their clinical utility

6.4 Biomarker discovery

6.5 Validation of biomarkers

6.5.1 Analytical validation of biomarkers

6.5.2 Clinical validation of biomarkers

6.6 Overview of the subsequent biomarker chapters in the book

Summary

7 Biomarkers for ischemia reperfusion injury and delayed graft function

mk:H1_1

7.1 Introduction

7.2 Ischemia-reperfusion injury and delayed graft function

7.2.1 Mechanism of IRI and DGF

7.2.2 Role of the immune system in IRI and DGF

7.2.2.1 Innate immune response

7.2.2.2 Adaptive immune response

7.2.3 Impact of IRI on transplant outcome

7.2.4 Risk factors

7.2.5 Role and limitation of allograft biopsy in the diagnosis of IRI/DGF

7.3 Need for novel biomarkers

7.4 Biomarkers for the detection of IRI and DGF

7.4.1 Donor biological fluid markers

7.4.1.1 Mitochondrial DNA

7.4.1.2 Complement C5a.

7.4.1.3 Soluble Klotho.

Notes:

Description based on publisher supplied metadata and other sources.

ISBN:

0-12-824070-9

0-12-824069-5

9780128240700

OCLC:

1547925290