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Kidney Transplantation, Bioengineering, and Regeneration: Kidney Transplantation in the Regenerative Medicine Era [Kõva köide]

Edited by (Director, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy), Edited by (Professor of Biomaterials ), Edited by (Section of Transplantation, Wake Forest University Baptist Medical Center Medical Center Boulevard Winston-Salem, NC, USA)
  • Formaat: Hardback, 1252 pages, kõrgus x laius: 276x216 mm, kaal: 3620 g
  • Ilmumisaeg: 23-Aug-2017
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128017341
  • ISBN-13: 9780128017340
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  • Formaat: Hardback, 1252 pages, kõrgus x laius: 276x216 mm, kaal: 3620 g
  • Ilmumisaeg: 23-Aug-2017
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128017341
  • ISBN-13: 9780128017340
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Kidney Transplantation, Bioengineering, and Regeneration investigates how the field of regenerative medicine is changing the traditional premises of solid organ transplantation, specifically within the field of kidney transplantation. In Section 1, chapters illustrate the state of the art in kidney transplantation as well as the research behind the bioengineering and regeneration of kidney organoids for therapeutic renal replacement. In Section II, chapters catalogue the technologies that are being developed and the methods that are being implemented to bioengineer or regenerate kidneys in order to restore function, while critically highlighting those technological advances which hold the most promise. The book thus encompasses clinical renal transplantation, tissue engineering, biomaterial sciences, stem cell biology, and developmental biology, as they are all applied to the kidney.

  • Focuses on the synergy between renal organ transplantation and regenerative medicine, highlighting the advances within transplantation, bioengineering, regeneration, and repair
  • Educates the transplant community on important regenerative medicine research pertinent to kidney transplantation
  • Develops a shared language for clinicians, surgeons, and basic researchers to reach across the fields of transplantation and regenerative medicine, and facilitate more productive investigation and research

Muu info

This cutting edge book investigates how the field of regenerative medicine is changing the traditional premises of kidney transplantation
List of Contributors
xvii
Biographies xxiii
Kidney Transplantation, Bioengineering, and Regeneration xxv
I KIDNEY TRANSPLANTATION
Section I Epidemiology of Kidney Disease and Transplantation
1 Epidemiology of End-Stage Renal Failure: The Burden of Kidney Diseases to Global Health
Matias Trillini
Norberto Perico
Giuseppe Remuzzi
1.1 The Global Burden of Noncommunicable Diseases
5(1)
1.2 Global Incidence and Prevalence of Chronic Kidney Disease and End-Stage Renal Disease
6(3)
1.3 Conclusions
9(4)
References
9(4)
2 Transplant Programs Worldwide and the Spanish Miracle
Rafael Matesanz
Beatriz Dominguez-Gil
Elisabeth Coll
Beatriz Mahillo
Gloria De La Rosa
Maria O. Valentin
2.1 Introduction
13(2)
2.2 The Spanish Model of Organ Donation and Transplantation
15(1)
2.3 Donor Coordination Network
16(1)
2.4 Specific Profile of the Donor Coordinator
16(1)
2.5 ONT as a Central Agency in Support of the System
17(1)
2.6 Quality Assurance Program in Deceased Donation
17(1)
2.7 Continuous Professional Training
18(1)
2.8 Close Cooperation With the Media
18(1)
2.9 Reimbursement of Donation and Procurement Activities
18(1)
2.10 Current Challenges in Organ Donation in Spain
19(1)
2.11 The 40 Donors per Million Population Plan
20(1)
2.12 Promoting the Identification of Possible Organ Donors Outside of the ICU and Considering Elective Nontherapeutic Intensive Care
20(2)
2.13 Fostering the Use of Organs From Expanded Criteria and Nonstandard Risk Donors
22(1)
2.14 Developing the Framework for the Practice of Donation After Circulatory Death
23(1)
2.15 Promoting Living Kidney Donation While Ensuring Comprehensive Donor Protection and Care
24(1)
2.16 Final Remarks
25(6)
References
25(6)
Section II Donor Selection and Allocation
3 The Deceased Kidney Donor
Hany El Hennawy
Jeffrey Rogers
3.1 Brain Death
31(1)
3.2 Deceased Donation
32(1)
3.3 Expanding the Donor Pool
32(5)
3.4 Conclusion
37(4)
References
37(4)
4 The Living Donor
Andrea Pietrabissa
Luigi Pugliese
Massimo Abelli
Elena Ticozzelli
Teresa Rampino
4.1 Background
41(1)
4.2 Donor Selection
42(1)
4.3 Surgical Techniques
43(4)
4.4 Outcome and Complications of the Surgery for the Donor
47(1)
4.5 Life Expectancy of the Donor
47(4)
References
48(3)
5 Criteria for Kidney Allocation in the United States
Linda Ohler
5.1 Introduction: History of Kidney Allocation
51(1)
5.2 Methods of Early Organ Sharing
52(1)
5.3 Evolution of National Organ Allocation Systems
52(5)
5.4 Conclusions
57(2)
References
57(2)
6 Strategies to Increase the Donor Pool
Michael A. Rees
David E. Fumo
6.1 Background
59(1)
6.2 Current Practices
60(2)
6.3 Deceased Donors
62(5)
6.4 Living Donation
67(1)
6.5 Donor and Recipient Education
68(2)
6.6 Unrelated Donors and Solicitation
70(1)
6.7 Donor Incentives
70(3)
6.8 Immunological Barriers
73(1)
6.9 Kidney Paired Donation
74(3)
6.10 Summary
77(10)
References
77(10)
Section III Kidney Preservation and Transplant Procedures
7 Kidney Preservation
Ina Jochmans
John M. O'Callaghan
Rutger J. Ploeg
Jacques Pirenne
7.1 Principles of Kidney Preservation
87(1)
7.2 Static Cold Storage
88(1)
7.3 Machine Perfusion Preservation
89(7)
7.4 Conclusion
96(5)
References
97(4)
8 Ex-vivo Normothermic Perfusion in Renal Transplantation
Sarah A. Hosgood
Michael L. Nicholson
8.1 Introduction
101(1)
8.2 The Origin of Normothermic Perfusion
101(1)
8.3 Technology
102(1)
8.4 Perfusion Conditions
102(2)
8.5 End Ex-vivo Normothermic Perfusion
104(1)
8.6 Intermediate Ex-vivo Normothermic Perfusion
104(1)
8.7 Kidney Manipulation/Conditioning
105(1)
8.8 Resuscitation
106(1)
8.9 Viability/Quality Assessment
106(1)
8.10 Summary & Conclusion
107(4)
References
107(4)
9 Kidney Transplant Recipient Surgery
Fabio Vistoli
Vittorio Perrone
Gabriella Amorese
Ugo Boggi
Giuseppe Orlando
9.1 Introduction
111(1)
9.2 Preparation of the Renal Graft (Synonymous to Bench Procedure or Benching)
112(3)
9.3 Standard Surgical Technique of Kidney Transplantation
115(8)
9.4 Surgical Considerations in Pediatric Recipients and Donors
123(1)
9.5 Orthotopic Kidney Transplantation
124(1)
9.6 Conclusions
124(3)
References
125(2)
10 Robotic-Assisted Kidney Transplantation
Ivo Tzvetanov
Pier C. Giulianotti
Giuseppe D'Amico
Raquel G. Roca
Enrico Benedetti
10.1 Introduction
127(1)
10.2 University of Illinois' Experience
127(3)
10.3 RAKT in the World
130(1)
10.4 Discussion
131(1)
10.5 Conclusion
132(3)
References
132(3)
11 Orthotopic Kidney Transplantation
Bulang He
11.1 Introduction
135(1)
11.2 Indications
135(1)
11.3 Surgical Techniques
135(4)
11.4 Conclusion
139(2)
References
140(1)
12 Kidney Transplantation Combined With Other Organs
Junichiro Sageshima
Linda Chen
Gaetano Ciancio
Alberto Pugliese
George W. Burke
12.1 Preamble
141(1)
12.2 Kidney Combined With Pancreas Transplantation
142(4)
12.3 Kidney Combined With Liver Transplantation
146(4)
12.4 Kidney Combined With Heart Transplantation
150(1)
12.5 Protection of Kidney by Other Organs
151(8)
Acknowledgements
152(1)
References
152(7)
13 Pediatric Renal Transplantation
Ashton Chen
Jen-Jar Lin
Andrew M. South
Abbreviations
159(1)
13.1 Introduction
160(1)
13.2 Surgical Aspect of Pediatric Renal Transplantation
161(1)
13.3 Desensitization
162(2)
13.4 Transplant Immunosuppression
164(4)
13.5 Metabolic Complications After Transplantation
168(1)
13.6 Recurrence
169(2)
13.7 Metabolic Diseases
171(1)
13.8 Cancer After Kidney Transplantation
171(1)
13.9 Infection
172(1)
13.10 Transition
173(14)
References
174(13)
Section IV Kidney Recipient: Before and Peritransplant
14 Indications for Renal Transplantation: Evaluation of Transplant Candidates
Opas Traitanon
Lorenzo Gallon
14.1 Introduction
187(1)
14.2 Indications and Contraindications
188(1)
14.3 Pretransplant Evaluation for Transplant Candidates
189(5)
14.4 Pretransplant Renal and Systemic Diseases
194(1)
14.5 Reevaluation After Waitlisting
195(4)
References
195(4)
15 Early Postoperative ICU Care of the Kidney Transplant Recipient
Xavier Wittebole
Diego Castanares-Zapatero
Michel Mourad
Virginie Montiel
Christine Collienne
Pierre-Francois Laterre
15.1 Introduction
199(1)
15.2 Fluid Therapy
199(3)
15.3 Central Venous Pressure Monitoring
202(1)
15.4 Dopamine and Other Medications
203(2)
15.5 Abdominal Compartment Syndrome and Renal Allograft Compartment Syndrome
205(1)
15.6 Other Considerations
206(1)
15.7 Conclusions
206(5)
References
206(5)
16 Approaches to Minimize Delayed Graft Function in Renal Transplantation
Maria Francesca Egidi
Domenico Giannese
Abbreviations
211(1)
16.1 Introduction
211(1)
16.2 Definitions
212(1)
16.3 Pathophysiology
212(1)
16.4 Imaging
213(1)
16.5 New Biomarkers and Predictive Models
213(1)
16.6 Prognostic Impact
214(1)
16.7 Interventions and Approaches to the Patient With DGF
215(1)
16.8 Conclusions
216(7)
References
217(6)
Section V Transplantation Immunology and Immunomodulation
17 Histocompatibility Testing in the Transplant Setting
Michael D. Gautreaux
17.1 Introduction
223(1)
17.2 Types of Rejection
223(2)
17.3 Histocompatibility Testing
225(8)
17.4 Conclusion
233(2)
References
233(2)
18 The Immune Response to the Allograft
Fiona Carty
Karen English
18.1 Introduction
235(1)
18.2 Ischemia Reperfusion
235(1)
18.3 T Cells and Mechanisms of Allorecognition
236(2)
18.4 B Cells
238(1)
18.5 The Immune Response Following Immunosuppression
239(1)
18.6 New Therapies for the Induction of Tolerance
240(1)
18.7 Discussion
241(6)
Acknowledgments
241(1)
References
241(6)
19 Induction Immunosuppression in Kidney Transplantation
Josep M. Grinyo
Oriol Bestard
19.1 Introduction
247(1)
19.2 Induction Immunosuppression in the Prevention of Acute Rejection
247(5)
19.3 Induction Immunosuppression in Low-Comorbidity Regimens
252(2)
19.4 Induction in High-Risk Patients
254(1)
19.5 Induction in the Prevention of Delayed Graft Function
255(4)
References
255(4)
20 Maintenance Immunosuppression in Kidney Transplantation
Monica Cortinovis
Giuseppe Remuzzi
Norberto Perico
20.1 Introduction
259(1)
20.2 Immunosuppressive Agents to Target the Alloimmune Response
260(1)
20.3 Corticosteroids
261(1)
20.4 Calcineurin Inhibitors
262(3)
20.5 Antiproliferative Agents
265(1)
20.6 The Mammalian Target of Rapamycin (mTOR) Inhibitors
266(4)
20.7 Costimulation Blockers
270(1)
20.8 Generic Immunosuppressive Medications
271(6)
References
272(5)
21 Novel Drugs in Kidney Transplantation
Sindhu Chandran
Flavio Vincenti
21.1 Introduction
277(1)
21.2 Therapies Targeting Delayed Graft Function
277(3)
21.3 Therapies Targeting Cellular Immunity
280(5)
21.4 Therapies Targeting Humoral Immunity
285(6)
References
287(4)
22 Hematopoietic Stem Cell Transplantation for Induction of Allograft Tolerance
Kiyohiko Hotta
Tetsu Oura
A. Benedict Cosimi
Tatsuo Kawai
22.1 Introduction
291(1)
22.2 Basic Studies in Rodents
291(3)
22.3 Preclinical Studies in Nonhuman Primates
294(1)
22.4 Clinical Studies
295(1)
22.5 Stanford University
296(1)
22.6 Massachusetts General Hospital
297(1)
22.7 Northwestern University
297(1)
22.8 Conclusion
298(5)
Acknowledgement
299(1)
References
299(4)
23 Regulatory T Cell Therapy in Transplantation
Scott Mcewen
Qizhi Tang
23.1 Introduction
303(1)
23.2 Treg Biology and Therapeutic Implications
304(2)
23.3 Tregs as Pharmaceuticals for Transplantation
306(4)
23.4 Clinical Experience Using Tregs
310(3)
23.5 Conclusions and Future Directions
313(6)
References
314(5)
24 Mesenchymal Stromal Cells to Improve Solid Organ Transplant Outcome: Lessons From the Initial Clinical Trials
Marlies E.J. Reinders
Johannes W. De Fijter
Maarten L. Zandvliet
Ton J. Rabelink
24.1 Introduction
319(1)
24.2 Mesenchymal Stromal Cells
319(1)
24.3 The Role of MSCs in Immune Modulation
320(1)
24.4 The Role of MSCs in Tissue Repair
321(1)
24.5 Experimental Studies With MSCs in Renal Transplantation
322(1)
24.6 Clinical Trials With MSCs After Renal Transplantation
323(5)
24.7 Conclusion and Future Directions
328(5)
References
328(5)
25 Renal Transplantation Across HLA and ABO Barriers
Shaifali Sandal
Robert A. Montgomery
25.1 Introduction
333(1)
25.2 Types of Antibodies
333(1)
25.3 Advantages of Desensitization
334(2)
25.4 Desensitization Modalities
336(9)
25.5 Kidney-Paired Donation
345(2)
25.6 The Future
347(10)
References
348(9)
Section VI Graft Monitoring Tools
26 Pathology of the Renal Allograft
Loredana Melchiorri
Christian C. Morrill
Gino Coletti
Paul Persad
26.1 Introduction
357(1)
26.2 Biopsy and Specimens
357(1)
26.3 Banff
358(4)
26.4 Chronic Rejection
362(4)
26.5 Infections
366(2)
26.6 Posttransplant Lymphoproliferative Disorders (PTLD)
368(1)
26.7 Drug Toxicities
369(4)
References
371(2)
27 Imaging-Based Monitoring of the Renal Graft
Corinne Deurdulian
Hisham Tchelepi
27.1 Introduction
373(1)
27.2 Renal Transplant Anatomy
373(1)
27.3 Ultrasound Imaging
373(3)
27.4 Complications: Nonvascular and Vascular
376(14)
27.5 Other Imaging Modalities
390(4)
27.6 New Developments in Transplant Ultrasound
394(5)
27.7 Conclusion
399(4)
References
399(4)
28 Immune Monitoring in Kidney Transplantation
Mark Nguyen
Anna Geraedts
Minnie Sarwal
28.1 Introduction
403(1)
28.2 Current Standards of Immune Monitoring
403(3)
28.3 Protocol Biopsies
406(1)
28.4 Disadvantages of Current Standards
406(1)
28.5 Noninvasive Monitoring
407(6)
28.6 Conclusion
413(6)
References
413(6)
29 Renal Function Measurements
Esteban Porrini
29.1 Introduction
419(1)
29.2 Methods to Evaluate Renal Function
419(1)
29.3 Estimation of Glomerular Filtration Rate
419(6)
29.4 Conclusions
425(4)
Acknowledgments
425(1)
References
425(4)
30 Pharmacokinetics and Genomics of Immunosuppressive Drugs
Marek Drozdzik
30.1 Introduction
429(1)
30.2 Tacrolimus
430(2)
30.3 Cyclosporine
432(2)
30.4 Sirolimus/Rapamycin
434(1)
30.5 Everolimus
435(1)
30.6 Mycophenolate
436(1)
30.7 Azathioprine
437(1)
30.8 Corticosteroids
438(1)
30.9 Belatacept
439(6)
References
440(5)
31 Gene Expression Technology Applied to Kidney Transplantation
Richard Danger
Sophie Brouard
31.1 Introduction
445(1)
31.2 Gene Expression Measure in Renal Transplantation
445(1)
31.3 Gene Expression Associated With Pre- or Peritransplantation Factors
446(2)
31.4 Gene Expression to Assess and Diagnose Acute Renal Rejection
448(2)
31.5 Microarray Analysis in Chronic Allograft Injury
450(1)
31.6 Immunosuppressive Drugs in Transplantation
451(2)
31.7 Conclusion
453(8)
References
453(8)
Section VII Early Posttransplant Immune Events
32 Acute Cellular Rejection
Madhav C. Menon
Paolo Cravedi
Fadi El Salem
32.1 Introduction
461(1)
32.2 Pathogenesis
461(2)
32.3 Risk Factors
463(1)
32.4 Clinical Features
464(1)
32.5 Pathology
464(4)
32.6 Treatment
468(2)
32.7 Impact and Prognosis of Acute Cellular Rejection
470(5)
References
470(5)
33 Acute Antibody-Mediated Rejection
Ivy A. Rosales
Robert B. Colvin
33.1 Introduction
475(1)
33.2 Risk Factors, Prevalence, and Clinical Presentation
475(1)
33.3 Pathogenesis
476(1)
33.4 Pathologic Findings
477(14)
References
485(6)
Section VIII Early and Late I Complications
34 Vascular Complications in Renal Transplantation
Hany El-Hennawy
Christian C. Morrill
Giuseppe Orlando
Alan C. Farney
34.1 Background
491(1)
34.2 Arterial Complications After Renal Transplantation
491(5)
34.3 Renal Vein Complications After Kidney Transplantation
496(1)
34.4 Lymphoceles
497(1)
34.5 Vascular Complications at the Backtable
498(5)
References
500(3)
35 Infections in Kidney Transplant Recipients
Aynaa Alsharidi
Deepali Kumar
Atul Humar
35.1 Timeline of Infections
503(1)
35.2 Pretransplant Screening of the Kidney Donor and Recipient
504(1)
35.3 Donor-Derived Infections
504(1)
35.4 Specific Infections
504(5)
35.5 Conclusions
509(4)
References
510(3)
36 Metabolic Disorders Following Kidney Transplantation
Quirino Lai
Francesco Pisani
36.1 Introduction
513(1)
36.2 Diabetes Mellitus
513(3)
36.3 Dyslipidemias
516(3)
36.4 Uric Acid Metabolism
519(6)
References
520(5)
37 Cancer After Kidney Transplantation
Renaud Snanoudj
Jacques Dantal
Celeste Lebbe
Christophe Legendre
37.1 Introduction
525(1)
37.2 Pathogenesis
525(2)
37.3 Cancer in Kidney Transplant Recipients
527(4)
37.4 Skin Cancers
531(2)
37.5 Focus on Posttransplantation Lymphoproliferative Disorders
533(10)
References
537(6)
38 Cardiovascular Disease and Renal Transplantation
Robert J. Applegate
P. Matthew Belford
Sanjay K. Gandhi
Michael A. Kutcher
Renato M. Santos
David X. Zhao
38.1 Introduction
543(1)
38.2 Assessment and Management of Cardiovascular Disease Pretransplantation
543(3)
38.3 Assessment and Management of Cardiovascular Disease Posttransplantation
546(6)
38.4 Conclusions
552(5)
References
552(5)
Section IX Long-term Outcomes
39 Graft and Patient Survival
Aneesha A. Shetty
Ekamol Tantissattamo
Bing Ho
Anton Skaro
Lihui Zhao
Samantha Montag
Michael Abecassis
Abbreviations
557(1)
39.1 Introduction
558(1)
39.2 Patient Survival
558(2)
39.3 Graft Survival
560(1)
39.4 Subclinical Allograft Dysfunction and Protocol Biopsies
561(5)
39.5 Combined Endpoints as Surrogate Measures for Kidney Transplant Outcome
566(2)
39.6 Conclusions
568(5)
References
568(5)
40 Urological Complications of the Renal Graft
Tristan Keys
Majid Mirzazadeh
40.1 Introduction
573(1)
40.2 Urological Complications Overview
573(3)
40.3 Early Onset Urological Complications of Renal Transplant
576(3)
40.4 Late Onset Urological Complications of Renal Transplantation
579(5)
40.5 Conclusions
584(5)
References
584(5)
41 Impact of De Novo Donor-specific Alloantibody in Primary Renal Allografts
Matthew J. Everly
41.1 Introduction
589(1)
41.2 Epidemiology
589(1)
41.3 Progression of DSA and Alloimmune Injury
590(1)
41.4 Good Graft Function With dnDSA
591(1)
41.5 IgG DSA Screening in Posttransplant Patients
591(1)
41-6 Prevention of dnDSA
592(1)
41.7 Therapeutic Options for Treatment of dnDSA
592(1)
41.8 Therapeutic Goals for Treatment of dnDSA
592(1)
41.9 Future Research for dnDSA
593(1)
41.10 Conclusion
593(4)
References
593(4)
42 De Novo and Recurrence of Renal Disease
Quirino Lai
Fabio Melandro
Francesco Pisani
42.1 Renal Disease Recurrence: Introduction
597(1)
42.2 Recurrence of Primary Disease
597(2)
42.3 Recurrence of Secondary Disease
599(3)
42.4 De Novo Disease
602(9)
References
604(7)
Section X Transplant Issues in Specific Patient Groups
43 Kidney Transplantation in the Elderly
Robert J. Stratta
Abbreviations
611(1)
43.1 Introduction
611(2)
43.2 New Kidney Allocation Policy in the United States
613(5)
43.3 Immunosuppression in the Elderly
618(1)
43.4 Graft Survival and Lifespan
619(1)
43.5 Death With a Functioning Graft
620(1)
43.6 Patient Survival and Longevity
620(1)
43.7 Living Donors
621(1)
43.8 Wake Forest Experience
621(6)
43.9 Conclusions
627(6)
References
627(6)
44 Dual Kidney Transplantation
Paolo Cravedi
Andrea Angeletti
Piero Ruggenenti
44.1 Introduction
633(1)
44.2 The Use of Expanded Criteria Donors as a Strategy to Increase the Donor Pool
633(1)
44.3 Preimplantation Biopsy Evaluation as an Option to Optimize the Use of Kidneys From Expanded Criteria Donors
634(3)
44.4 Is There an Age Limit to Donate Kidneys Allocated According to Pretransplant Biopsy Score?
637(1)
44.5 Is There an Age Limit to Receive a Dual Kidney Transplant?
637(1)
44.6 Operative Technique and Immunosuppressive Therapy
638(1)
44.7 Complications of Dual Kidney Transplantation
638(1)
44.8 How to Further Improve the Location and Performance of Organs From Expanded Criteria Donors?
639(1)
44.9 Conclusions
640(3)
Acknowledgments
640(1)
References
640(3)
45 Kidney Transplantation in the Diabetic Patient
Angelika C. Gruessner
Rainer Wg Gruessner
Abbreviations
643(1)
45.1 Epidemiology, Classification and Consequences of Diabetes Mellitus
643(1)
45.2 Diabetic Kidney Disease and Transplant Treatment Options
644(9)
References
649(4)
46 Kidney Transplantation in the Hepatitis C Infected Recipient
Roberta Angelico
Giuseppe Iaria
Mario Angelico
46.1 Introduction
653(1)
46.2 Epidemiology and Risk Factors of HCV Infection in Patients With Chronic Renal Disease
654(1)
46.3 Screening and Diagnosis of HCV Infection in Patients With ESRD
654(1)
46.4 Evaluation of the HCV-Related Liver Disease
655(1)
46.5 Natural History of HCV Infection in Patient With End-Stage Renal Disease
656(1)
46.6 Natural History of HCV Infection After KT
656(2)
46.7 Immunosuppression in HCV-Positive KT Recipients
658(1)
46.8 Current Perspectives of Treatment of HCV-Infected Patients on Hemodialysis and in KT Recipients With Antivirals
659(6)
References
660(5)
47 Pregnancy After Kidney Transplantation
Marialuisa Framarino-Dei-Malatesta
47.1 Introduction: From the Past to the Present
665(1)
47.2 Counseling
665(2)
47.3 Effect of KT on Pregnancy
667(4)
47.4 Effect "of Pregnancy on the Graft
671(1)
47.5 Delivery
672(1)
47.6 Breast-Feeding
672(1)
47.7 Algorithm for Prenatal and Pregnancy Care in Transplanted Patients
673(4)
References
674(3)
48 Nutrition of the Kidney Transplant Recipients
Paolo Dionigi
Mario Alessiani
48.1 Introduction
677(1)
48.2 Pretransplant Nutrition Assessment and Management
677(2)
48.3 Nutrition and the Live Kidney Donor
679(1)
48.4 Posttransplant Nutritional Management in Adults
679(2)
48.5 Nutrition Management After Pediatric Kidney Transplantation
681(6)
References
681(6)
Section XI Ethics and Costs
49 Kidney Transplantation in Developing Countries
Goce Spasovski
Mirela Busic
Mirjana S. Matovinovic
Francis L. Delmonico
49.1 Introduction
687(1)
49.2 Global Perspective of Kidney Disease and Renal Replacement Therapy
688(1)
49.3 Kidney Transplantation in Developing Countries
689(8)
49.4 Conclusions
697(2)
References
697(2)
50 Health-Related Quality of Life Outcomes After Kidney Transplantation
Aneesha A. Shetty
Jason A. Wertheim
Zeeshan Butt
Abbreviations
699(1)
50.1 Introduction
699(1)
50.2 Tools to Measure HRQOL
700(1)
50.3 Kidney Transplantation Improves HRQOL
701(2)
50.4 Factors Influencing HRQOL After Kidney Transplant
703(2)
50.5 Conclusions
705(4)
References
706(3)
51 Costs of Kidney Transplantation
Charles Strom
Yanik Bababekov
David Axelrod
51.1 Introduction
709(1)
51.2 Financing of End Stage Renal Care
709(2)
51.3 Clinical and Economic Benefits of Renal Transplantation
711(1)
51.4 Economic Implications of Donor Characteristics
712(2)
51.5 Patient Characteristics
714(1)
51.6 The Economic Implications of Novel Approaches to Increase Access to Organ Transplant
715(1)
51.7 Summary and Conclusions
716(5)
References
717(4)
Section XII Unmet Needs
52 Kidney Transplantation: Have the Promises Been Kept and Needs Met
Charles Strom
Eliot Heher
A. Benedict Cosimi
52.1 Introduction
721(1)
52.2 Historical Background
722(1)
52.3 Promises and Needs Met
723(3)
52.4 Promises and Needs Remaining
726(7)
52.5 Conclusions
733(4)
References
734(3)
53 Innovations in Kidney Transplant Research
Sarwat Ahmad
Eric Siskind
Jonathan S. Bromberg
Abbreviations
737(1)
53.1 Innate Lymphoid Cells
738(2)
53.2 Microbiota
740(5)
53.3 Stromal Cells
745(12)
References
749(8)
II KIDNEY BIOENGINEERING AND REGENERATION
Section I Introduction
54 Converging Organ Transplantation Towards Regenerative Medicine
Ravi Katari
Riccardo Tamburrini
Lauren Edgar
Giuseppe Orlando
Abbreviations
757(1)
54.1 Introduction
757(2)
54.2 The Demand for Transplantable Organs
759(1)
54.3 Shortcomings of Organ Transplantation
759(1)
54.4 Challenges Associated With Antirejection Therapy
760(1)
54.5 Regenerative Medicine and Organ Bioengineering
760(5)
54.6 Closing Remarks
765(4)
References
765(4)
55 A Systems Engineering Approach to Restoring Kidney Structure and Function
David F. Williams
55.1 Introduction
769(1)
55.2 The Targets of Engineered Solutions to Kidney Failure
770(5)
55.3 Specific Engineering Challenges in Restoring Kidney Function
775(6)
55.4 Conclusions
781(6)
References
782(5)
Section II Kidney Development
56 Kidney Development in the Mammal
Melissa H. Little
56.1 Introduction
787(1)
56.2 Formation of the Excretory System from the Intermediate Mesoderm
787(2)
56.3 Initiation of the Metanephros and Early Morphogenetic Events
789(1)
56.4 A Progenitor for the Collecting Ducts Within the Branching Ureteric Epithelium
789(3)
56.5 The Nephron Progenitor Population Balancing Self-Renewal With Nephron Induction
792(1)
56.6 A Stromal Progenitor Population Gives Rise to Perivascular and Mesangial Cells and Regulates Kidney Patterning
793(1)
56.7 Vascular Progenitors and Their Role in Formation of the Renal Vasculature
793(1)
56.8 Nephron Induction, Segmentation, and Functionalization
794(1)
56.9 Cessation of Nephrogenesis
795(1)
56.10 Conclusion
795(6)
References
796(5)
57 Renal Branching Morphogenesis
Joshua Blake
Norman D. Rosenblum
Abbreviations
801(1)
57.1 Introduction
801(1)
57.2 Overview of Renal Branching Morphogenesis
802(1)
57.3 Specification and Patterning of the Nephric Duct
803(2)
57.4 Specification of the Ureteric Bud Site
805(2)
57.5 Branching of the Ureteric Bud and Its Derivatives
807(3)
57.6 Cessation of Renal Branching Morphogenesis
810(1)
57.7 Conclusions and Implications for Tissue Regeneration
811(6)
Acknowledgments
811(1)
References
811(6)
Section III Bioengineering
58 Principles of Stem Cell Biology Applied to the Kidney
Brooke E. Chambers
Rebecca A. Wingert
58.1 The Fundamental Cellular Principles of Living Systems
817(1)
58.2 Cellular Diversity Through Differentiation
818(1)
58.3 Revelations of Embryonic Cell Potency and Differentiation From Developmental Biology
819(1)
58.4 The Discovery of Adult Stem Cells, Their Properties, and Residence in Homes Called Niches
820(2)
58.5 The Stem Cell Paradigm, Genomic Equivalence, and Plasticity of Cellular States
822(1)
58.6 Kidney Stem Cells During Development
822(2)
58.7 The Adult Kidney: Conflicting Evidence About Sternness, Plasticity, and Dedifferentiation
824(1)
58.8 Conclusions and Future Prospects
825(4)
Acknowledgments
825(1)
References
825(4)
59 Extracellular Matrix Biology Applied to the Kidney
Rachel Lennon
59.1 Introduction
829(1)
59.2 Extracellular Matrix
829(2)
59.3 Extracellular Matrix in Kidney Health and Disease
831(5)
59.4 Matrix-Targeted Therapy
836(2)
59.5 Concluding Comments
838(5)
References
838(5)
60 Interplay Between Growth Factor Receptors, Small GTPases, and Mechanical Stress in the Maintenance of Kidney Glomerular Homeostasis
Manuel Chiusa
Xiwu Chen
Roy Zent
Ambra Fozzi
Abbreviations
843(1)
60.1 Introduction
843(2)
60.2 Growth Factors and Glomerulosclerosis
845(4)
60.3 Small Rho GTPase and Glomerulosclerosis
849(3)
60.4 Cytoskeletal Proteins
852(1)
60.5 Mechanical Stress
853(1)
60.6 Conclusions
854(7)
Acknowledgments
855(1)
References
855(6)
61 Bioengineering Approach to Immunomodulation
Lauren Brasile
Bart Stubenitsky
61.1 Introduction
861(1)
61.2 An Alternative Approach
862(7)
61.3 Conclusions
869(4)
References
870(3)
62 Principles of Organ Bioengineering
Abritee Dhal
Matthew Brovold
Anthony Atala
Shay Soker
62.1 Introduction
873(1)
62.2 Tissue Engineering
873(1)
62.3 Liver
874(1)
62.4 Heart
874(1)
62.5 Lung
874(1)
62.6 Pancreas
875(1)
62.7 Intestine
875(1)
62.8 Conclusions
875(2)
References
876(1)
63 Recellularization of Kidney Scaffold With Stem Cells
Marina Figliuzzi
Giuseppe Remuzzi
Andrea Remuzzi
63.1 Introduction
877(1)
63.2 Stem Cells for Kidney Tissue Engineering
878(2)
63.3 Cell Seeding in the Rat Kidney
880(2)
63.4 Cell Seeding in the Kidney of Large Animals
882(1)
63.5 Cell Seeding in the Human Kidney
883(1)
63.6 Conclusion
883(6)
Acknowledgments
884(1)
References
884(5)
Section IV Bioreactors and Biomaterials
64 Bioreactors for Cell Culture Systems and Organ Bioengineering
Chiara Attanasio
Paolo A. Netti
64.1 Introduction
889(1)
64.2 Bioreactors Design: General Parameters and Specific Features
890(1)
64.3 Bioreactor Systems for Tissue Engineering
891(1)
64.4 Impact of Biomimetic and Microenvironmental Stimuli on Tissue Development
892(1)
64.5 Bone
892(3)
64.6 Bioreactors and Whole-Organ Bioengineering
895(2)
64.7 Conclusions and Remarks
897(4)
Acknowledgment
897(1)
References
897(4)
65 Synthetic Biomaterial for Regenerative Medicine Applications
Tiziana Nardo
Irene Carmagnola
Francesca Ruini
Silvia Caddeo
Stefano Calzone
Valeria Chiono
Gianluca Ciardelli
65.1 Introduction
901(3)
65.2 Relevant Biomaterial Properties in TE Field
904(2)
65.3 Nondegradable Polymers
906(1)
65.4 Degradable Polymers
907(2)
65.5 Hydrogels
909(3)
65.6 Polyurethanes
912(3)
65.7 Conclusions and Future Directions
915(8)
Acknowledgments
915(1)
References
915(8)
66 Immune Responses to Biomaterials Used in Renal Engineering
David F. Williams
66.1 Introduction
923(1)
66.2 The Immunological Basis of Biocompatibility
924(3)
66.3 Immunological Aspects of Biocompatibility Phenomena in Renal Technologies
927(4)
66.4 Conclusions
931(6)
References
931(6)
Section V Regeneration
67 Regeneration of Kidney From Human Reprogrammed Stem Cells
Melissa H. Little
Kenji Osafune
67.1 Introduction
937(1)
67.2 The Origin of the Cellular Components of the Kidney
938(1)
67.3 Possible Options for Regenerating Kidney Tissues
939(2)
67.4 Direct Differentiation of Pluripotent Stem Cells to Kidney Progenitor States
941(4)
67.5 Challenges to the Generation of Kidney From Pluripotent Stem Cells
945(2)
67.6 Possible Applications of Stem-Cell Derived Renal Cells
947(3)
67.7 Conclusion
950(7)
Acknowledgments
951(1)
References
951(6)
68 Bioprinting Complex 3D Tissue and Organs
Carlos Kengla
Amritha Kidiyoor
Sean V. Murphy
68.1 Introduction
957(1)
68.2 Philosophy
958(1)
68.3 Technological Strategies
959(3)
68.4 Materials
962(2)
68.5 Cells
964(2)
68.6 Progress and Challenges for Kidney Bioprinting
966(1)
68.7 Conclusion
967(6)
References
967(6)
69 Principles of Kidney Regeneration
Maria L. Angelotti
Francesca Becherucci
Benedetta Mazzinghi
Anna Peired
Paola Romagnani
69.1 Introduction
973(1)
69.2 Kidney Regeneration From Evolution to Mammalian Renal Development
973(3)
69.3 Clinical and Experimental Evidence of Kidney Regeneration
976(2)
69.4 Renal Progenitor Cells in Adult Kidney and Their Role in Glomerular and Tubular Regeneration
978(6)
69.5 Conclusions
984(5)
References
985(4)
70 Markers of Repair and Regeneration in the Marginal Kidney
Stephen J. Walker
Susan Y. Zhao
70.1 Introduction
989(1)
70.2 Defining the Marginal Kidney
989(1)
70.3 Markers of Injury
990(2)
70.4 The Renal Repair/Regeneration Process
992(1)
70.5 Evaluating Posttransplantation Renal Function
993(1)
70.6 Molecular Profiling in the Field of Kidney Transplantation
994(1)
70.7 Conclusions
994(3)
References
995(2)
71 Nephron Repair in Mammals and Fish
Zhenzhen Peng
Veronika Sander
Alan J. Davidson
71.1 Introduction
997(1)
71.2 Proximal Tubule Repair in Mammals
997(2)
71.3 Proximal Tubule Repair in Fish
999(1)
71.4 Neonephrogenesis in Fish
1000(2)
71.5 Conclusion
1002(3)
References
1002(3)
72 Imaging of Glomerular Regeneration
Janos Peti-Peterdi
Kengo Kidokoro
Anne Riquier-Brison
72.1 High-Power Multiphoton Microscopy Imaging: A Technical Breakthrough for Glomerular Studies
1005(1)
72.2 Intravital Imaging of the Glomerulus With Conventional Huorescent Probes
1006(2)
72.3 The Combination of Two State-of-the-Art Technologies for Glomerular Studies: Intravital Imaging and Mouse Genetics
1008(1)
72.4 Serial Multiphoton Microscopy Imaging of the Remodeling Glomerulus
1009(1)
72.5 Conclusion
1009(4)
Acknowledgment
1009(1)
References
1009(4)
73 Reversibility of Renal Fibrosis
Christos E. Chadjichristos
Panagiotis Kawadas
Jean-Claude Dussaule
Ahmed Abed
Christos Chatziantoniou
73.1 Introduction
1013(1)
73.2 Current Mediators of Renal Fibrosis
1013(3)
73.3 New Mediators of Renal Fibrosis
1016(3)
73.4 Conclusion
1019(6)
References
1019(6)
74 Pharmacological Induction of Kidney Regeneration
Elena Gagliardini
Ariela Benigni
Norberto Perico
74.1 Introduction
1025(1)
74.2 Kidney Regeneration in Experimental AKI
1025(4)
74.3 Kidney Regeneration in Experimental CKD
1029(3)
74.4 Kidney Regeneration in Humans
1032(1)
74.5 Conclusion
1033(6)
Acknowledgments
1034(1)
References
1034(5)
75 Developmental Approaches to Kidney Regeneration
Valentina Benedetti
Barbara Imberti
Christodoulos Xinaris
Giuseppe Remuzzi
75.1 Introduction
1039(1)
75.2 Transplantation of Embryonic Kidney Tissues
1039(4)
75.3 Engineering Kidney Tissue Using Embryonic Kidney Cells
1043(3)
75.4 Blastocyst Complementation
1046(1)
75.5 Conclusions
1047(6)
Acknowledgments
1047(1)
References
1048(5)
Section VI Adult Cells for Regeneration
76 Nephron Progenitors
Ilaria Santeramo
Bettina Wilm
Patricia Murray
76.1 Introduction
1053(1)
76.2 Sources of Nephron Progenitor Cells
1054(3)
76.3 Characterization of Nephron Progenitor Cells Isolated From Kidneys
1057(1)
76.4 The Potential of Nephron Progenitors in Regenerative Medicine
1058(9)
References
1062(5)
77 Urine Progenitor Cells for Potential Application in Renal Tissue Repair
Peng Li
Xiongbing Lu
Junhong Deng
Andrea Peloso
Yuanyuan Zhang
77.1 Introduction
1067(1)
77.2 Stem Cell Properties of USCs
1068(3)
77.3 Generation of iPSCs From USCs (U-iPSCs)
1071(1)
77.4 Origination of USCs
1071(1)
77.5 Advantages of USCs
1072(1)
77.6 Future Directions
1072(3)
Acknowledgments
1072(1)
References
1072(3)
78 Endothelial Progenitor Cells in Kidney Disease
Michael S. Goligorsky
78.1 Introduction
1075(1)
78.2 EPC Ontogeny and Presumed Role
1075(2)
78.3 EPC Dysfunction
1077(1)
78.4 EPC Transplantation
1077(1)
78.5 EPC Secretome and Angiocrine Signaling
1078(1)
78.6 EPC in Sepsis: Use of Scaffolds to Adoptively Transfer EPC
1079(1)
78.7 EPC-Induced Macrophage Polarization
1079(1)
78.8 Use of EPC Extract to Combat CKD and Fibrogenesis
1079(1)
78.9 EPC Rejuvenation: NAD, SIRTI, Ebselen, mTOR, AMPK, Inhibitors of GSK-3ß
1079(6)
Acknowledgments
1080(1)
References
1080(5)
Section VII Cell Therapy For Renal Tissue Repair
79 Mesenchymal Stromal Cells for Acute Renal Injury
Cinzia Rota
Serge Cedrick Mbiandjeu Toya
Marina Morigi
79.1 Introduction
1085(1)
79.2 Mesenchymal Stem Cells
1085(7)
79.3 Conclusions and Perspectives
1092(5)
References
1093(4)
80 Amniotic Fluid Cells: Kidney Injury and Regeneration
Stefano Da Sacco
Astgik Petrosyan
Laura Perin
80.1 Introduction
1097(1)
80.2 Amniotic Fluid
1097(1)
80.3 Amniotic Fluid Cells: Selection, Characterization and Expansion
1098(3)
80.4 Amniotic Fluid Therapeutic Potential in Renal Injury
1101(2)
80.5 Kidney Regeneration and Bioengineering
1103(1)
80.6 Concluding Remarks
1104(5)
References
1104(5)
81 Renal Cells From Spermatogonial Germline Stem Cells for Protection Against Kidney Injury
Sharmila Fagoonee
Letizia De Chiara
Elvira Smeralda Famulari
Lorenzo Silengo
Fiorella Altruda
81.1 Introduction
1109(1)
81.2 Spermatogonial Stem Cells
1110(1)
81.3 Germline Cell-Derived Pluripotent Stem Cells
1110(4)
81.4 Conclusion
1114(5)
Acknowledgments
1114(1)
References
1114(5)
Section VIII Future Perspective
82 Kidney-on-a-Chip: Technologies for Studying Pharmacological and Therapeutic Approaches to Kidney Repair
Rosalinde Masereeuw
Jelle Vriend
Martijn J. Wilmer
82.1 Introduction
1119(1)
82.2 In Search for Translational Cell Models
1120(3)
82.3 Engineered Renal Models: From 1D to 3D
1123(7)
82.4 Future Prospects in Regenerative Nephropharmacology
1130(5)
References
1130(5)
83 Renal Replacement Devices
Christopher J. Pino
H. David Humes
83.1 Overview of Renal Replacement
1135(1)
83.2 Membranes for Small-Solute Clearance
1136(5)
83.3 Endothelialized Membranes and Renal Epithelial Cell (REC) Therapy
1141(4)
83.4 Biomimetic Immunomodulatory Devices
1145(1)
83.5 Future Prospects
1146(5)
References
1147(4)
84 Xenotransplantation and Kidney Regenerative Technology
Kazuhiko Yamada
Masayuki Tasaki
Adam Griesemar
Jigesh Shah
84.1 Introduction
1151(1)
84.2 Regeneration of the Kidney
1151(1)
84.3 Cell-Based Therapies
1151(2)
84.4 De Novo Organ Generation
1153(1)
84.5 Xenotransplantation
1154(4)
84.6 Conclusion
1158(5)
References
1158(5)
85 Embryonic Organoid Transplantation
Shinya Yokote
Takashi Yokoo
85.1 Introduction
1163(1)
85.2 Embryonic Kidney Transplantation for Kidney Regeneration
1163(1)
85.3 De Novo Kidney Regeneration Using the Organogenic Niche Method
1164(1)
85.4 Conclusion
1165(2)
References
1165(2)
86 Lineage Reprogramming Toward Kidney Regeneration
Yun Xia
Nuria Montserrat
Josep M. Campistol
Juan Carlos Izpisua Belmonte
86.1 The Waddington Landscape: "Topping" Pluripotency
1167(1)
86.2 Reprogramming: Reverting Development
1167(1)
86.3 In vitro Lineage Specification: Choosing the Wanted Route
1168(2)
86.4 Representing Lineage Reprogramming From a Mathematical Point of View
1170(1)
86.5 How to Quantify Cellular Status During Lineage Reprogramming
1170(1)
86.6 Mathematical Approaches to Quantify Lineage Specification
1171(2)
86.7 Conclusion
1173(4)
Acknowledgments
1173(1)
References
1173(4)
87 Regenerating Kidney Structure and Function: An Industry Perspective
Joydeep Basu
Timothy A. Bertram
John W. Ludlow
87.1 Introduction
1177(1)
87.2 Biomaterials: An Industry Perspective
1177(1)
87.3 Decell/Recell---the Ultimate Biomaterial Platform?
1178(1)
87.4 Selection of Biomaterials for Tissue Engineering: Kidney as an Illustrative Example
1179(2)
87.5 Biomaterial Candidates for Renal Tissue Engineering
1181(2)
87.6 Cells for Renal Tissue Engineering
1183(1)
87.7 NKA Product Potency
1184(5)
References
1186(3)
Index 1189
Giuseppe Orlando, MD, PhD, Marie Curie Fellow, is an Associate Professor and a kidney and pancreas transplant surgeon scientist at the Wake Forest University School of Medicine, in Winston Salem, USA. His research aims at developing platforms for the bioengineering and regeneration of transplantable organs, and at developing therapies to enhance the innate ability of the human body to repair itself after damage. His literature output aims at bridging organ transplantation to regenerative medicine. Giuseppe Remuzzi, MD, FRCP, is Director of Mario Negri Institute for Pharmacological Research IRCCS and Chiara Fama Professor of Nephrology and the University of Milan. From 1996 until 2013, he was Director of the public-private Department of Immunology and Transplant Medicine (a collaboration between the Ospedali Riuniti of Bergamo and the Mario Negri Institute) and from 1999 until 2018, he was also the Head of the Division of Nephrology and Dialysis. From 2011 until 2015, he was Director of the Department of Medicine of the Azienda Ospedaliera Papa Giovanni XXIII (formerly the Ospedali Riuniti) of Bergamo. In June 2015, he was nominated Chiara Fama Professor of Nephrology at the University of Milan. Prof. Remuzzi was President of the International Society of Nephrology (ISN) for the biennium 2013-2015. From 2019, he has been the Vice President of the Italian Institute for Planetary Health (IIPH). He has been a member of the Consiglio Superiore di Sanità since February 2019.

Prof. Remuzzis main research interests include the causes of glomerulonephritis and the mechanisms of progression of kidney diseases. He has also conducted many studies in the field of transplant rejection. In recognition of his achievements, he received many national and international awards, among them the ISN Jean Hamburger Award in 2005 during the World Congress of Nephrology in Singapore, the John P. Peters Award (American Society of Nephrology 2007, San Francisco), the ISN AMGEN Award (World Congress of Nephrology: WCN 2011, Vancouver), the International Award "Luis Hernando" (Iñigo Alvarez de Toledo Renal Foundation FRIAT: Madrid, Spain) and the Lennox K. Black International Prize for Excellence in Medicine” (Thomas Jefferson University, Philadelphia). ). Prof. Remuzzi was honored by the Italian President of the Republic with the title of Cavaliere di Gran Croce in 2022. Prof. Remuzzi is the author of more than a thousand publications in international medical journals and has written 24 books.

Professor Williams has had 48 years experience in biomaterials, medical device and tissue engineering, working mostly at the University of Liverpool, UK where he was ultimately Professor of Biomaterials and Biomedical Engineering, Director of the UK Centre for Tissue Engineering and Senior Pro-Vice Chancellor of the University. During his career he has published over 30 books and 400 papers: his latest book, Essential Biomaterials Science, was published by Cambridge University Press in June 2014. He was Editor-in-Chief of Biomaterials, the worlds leading journal in this field between 2000 and 2014. He has received the major awards from the US, European and Indian societies of biomaterials including the Founders Award of the US Society for Biomaterials in 2007, and received the prestigious Acta Biomaterialia Gold Medal in 2012. In 1999 he was elected as a Fellow of the Royal Academy of Engineering and is a Foreign Fellow of the Indian National Academy of Engineering and a Fellow of the American Institute of Medical and Biological Engineering, all in recognition of his contributions to engineering in medicine. He was global President of the Tissue Engineering & Regenerative Medicine International Society from 2013-2015. He was a scientific advisor to several divisions of the European Commission during the 1990s and wrote several opinions on which European actions were taken. He has, over the last 20 years, given evidence in several major product liability and patent legal cases in the USA, Europe and Australia.

Professor Williams left the University of Liverpool in 2007. While retaining the title of Emeritus Professor at Liverpool, he is currently Professor and Director of International Affairs, Wake Forest Institute of Regenerative Medicine, North Carolina, USA. In addition, he is a Visiting Professor in the Christiaan Barnard Department of Cardiothoracic Surgery, Cape Town, South Africa, a Adjunct Professor at the University of Technology, Sydney, Australia, and a Guest Professor, at Tsinghua University, Beijing, and Advisory Professor at Shanghai Jiao Tong University, China. He is Visiting Chair Professor of Biomedical Materials, Taipei Medical University, Taiwan. In Cape Town, along with Professor Peter Zilla, the current Chris Barnard Professor of Surgery, he has formed a company that will produce low cost but high technology medical devices that can be used with minimally invasive procedures to treat young adults in sub-Sarah Africa, who are suffering from rheumatic heart disease but currently have no therapies available to them.