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×î×¼µÄÁùºÏ²ÊÂÛ̳ Division of Medicine

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Transplantation

Prof. Reza Motallebzadeh, Prof. Stephen Marks, Dr Rhys Evans, and Dr Daniyal Jafree lead collaborative, multidisciplinary and translational research into chronic kidney disease and renal transplantation. We hope to understand the immune mechanisms underlying development of allograft failure and rejection in solid organ transplantation. Our aim is to develop new knowledge and practices to improve long-term outcomes for patients receiving a kidney transplant.

Our work

Despite improvements in short- and medium-term graft survival rates after renal transplantation, long-term graft survival has remained largely unchanged for the last twenty years, with recipients either dying with a functioning graft or suffering graft loss due to infection and/or chronic alloimmune rejection. Furthermore, balancing the benefits and adverse effects of immunosuppression to extend graft survival remains a challenge.

We focus on collaborative, multidisciplinary, and translational research in chronic kidney disease and renal transplantation. The research themes are underpinned by a commitment to developing innovative collaborations with academic and industrial partners and are primarily focused on understanding mechanisms of allograft failure and improving long-term graft and patient survival outcomes in renal transplantation.

Our Centre is currently working on the following areas of translational science and clinical research:

  • Delineating the role of the host microbiota in renal transplantation.
  • Identification of novel blood, urine, and tissue biomarkers of acute rejection and transplant injury to assist personalised immunosuppression in paediatric renal transplant recipients.
  • Understand the role of tissue-resident NK cells in the control of human cytomegalovirus infection.
  • Spatial and molecular profiling of kidney lymphatic vessels in kidney allograft rejection.
  • The BKV viral serotype mismatch of the UK donor and renal transplant recipient population predicts post-transplant BKV viraemia.
  • Investigating the impact of sodium on alloimmune responses.
  • Study of B cell responses to SARS-CoV-2 vaccination in end-stage kidney disease and defining the basis of a hyporesponsive immune phenotype.
  • Donor-derived cell-free DNA: a liquid biopsy following solid organ transplantation.
  • Developing 3D renal organoids to study renal fibrosis.
  • Qualitative assessment of the impact of human cytomegalovirus infection in kidney transplantation.
  • The role of complement immune attack and regulation in kidney transplant biopsies.
  • Investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children.

Surgeon with forehead lamp concentrating on a transplant

Translational Research

Improving Graft Outcomes

Integrating immunological, metabolite and microbiome data to predict clinical outcomes in kidney transplantation

The composition of the microbiota and their metabolites could elicit signals that promote either an enhanced or diminished immune response against a kidney transplant. We aim to develop a better understanding of the changes to the gut microbiota and metabolites produced by them that can predict the course and heterogeneity of alloimmune responses.

Collaborators

  • Professor Reza Motallebzadeh
  • Dr Mona Bajaj-Elliot (GOS Institute of Child Heath, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Anne Pesenacker (Institute of Immunity & Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Simon Eaton (GOS Institute of Child Heath, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Alan Salama (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Jennifer Rohn (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Claudio Mauri (Institute of Immunity & Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Alan Salama (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
Spatial and molecular profiling of kidney lymphatic vessels in kidney allograft rejection

The lymphatic vasculature clears fluid and macromolecules from the tissue microenvironment and acts as a highway for migrating leukocytes. There is however limited information beyond traditional immunohistochemical assessment in human organs such as the kidney. We use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney, with the aim of delineating novel structural and molecular features that might be of relevance to chronic alloimmunity.

Collaborators

  • Professor Reza Motallebzadeh
  • Professor David Long (GOS Institute of Child Heath, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Daniyal Jafree (GOS Institute of Child Heath, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Menna Clatworthy (Cambridge Institute of Therapeutic Immunology & Infectious Disease, Cambridge University)
  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
Understanding the role of tissue-resident NK cells in the control of human cytomegalovirus infection

Human cytomegalovirus (HCMV), one of the most frequent infectious complications after kidney transplantation, can lead to graft rejection and death. Natural killer (NK) cells can counter HCMV and are present in circulating blood, but we have also recently identified NK cells within donor kidneys. We aim to understand if kidney-resident NK cells can better control HCMV than their circulating counterparts. We can then determine if some donor's kidneys because they are better armed with kidney-resident NK cells, are better at controlling HCMV in recipients. Our work will ultimately help in the design of novel therapies against HCMV.Ìý

Collaborators

  • Professor Reza Motallebzadeh
  • Dr Matthew Reeves (Institute of Immunity & Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Dimitra Peppa (Institute of Immunity & Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Victoria Male (Faculty of Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College)
The BKV viral serotype mismatch of the UK donor and renal transplant recipient population predicts post-transplant BKV viraemiaÌý

BK polyomavirus (BKV) has a seroprevalence of >80%. Viraemia occurs in 10% of kidney transplantation recipients and may result in premature allograft failure. Given emerging evidence that the disease is donor-derived, we aim to determine the correlation between donor/recipient BKV serotype mismatch and infection risk, using neutralisation profiles to infer viral serotypes individuals have encountered.Ìý

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  • Professor Alan Salama (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Matthew Reeves (Institute of Immunity and Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
Investigating the impact of sodium on alloimmune responses in kidney transplant recipients

Recent research by our team and others has shown that increased extracellular sodium, which may be the result of a high salt (sodium chloride) diet, can impact immunity. The overall effect of increasing extracellular sodium is to make the immune system more inflammatory and we have shown that patients with inherited salt-losing diseases have a dysregulated immune system with dampened IL-17 responses. ÌýWe are now investigating how sodium impacts alloimmune responses, and we will undertake a pilot study to determine the effect of salt depletion on immunity in kidney transplant recipients. This work is funded through an innovation grant from Kidney Research UK and a project grant from St. Peter’s Trust.

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  • Dr Rhys Evans (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Alan Salama (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Reza Motallebzadeh (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳, Research Dept of Surgical Biotechnology, ×î×¼µÄÁùºÏ²ÊÂÛ̳ & Institute of Immunity and Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Stephen Walsh (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)

Biomarker Discovery

Development of a point-of-care assay for monitoring rejection after renal transplantation

A novel point-of-care device to monitor urinary chemokines serially in renal transplant recipients and identify recipients with incipient allograft injury. Immune-based biomarkers offer the potential for identifying patients at risk for graft rejection and for individualizing immunosuppression therapy.

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  • Professor Reza Motallebzadeh
  • Professor Manish Tiwari (Dept of Mechanical Engineering, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor Stavroula Balabani (Dept of Mechanical Engineering, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Mark Harber (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Dr Arnab Guha (Department of Mechanical Engineering, Birla Institute of Technology & Science, India)
  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
Identification of novel blood, urine, and tissue biomarkers of acute rejection and transplant injury to assist personalised immunosuppression in paediatric renal transplant recipients

This study aims to understand the aetiopathogenesis of acute rejection and transplant injury to improve longer-term outcomes in children and young people, funded by Kidney Research UK Laurence Isaacson PhD award.

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  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • Professor David Long (GOS Institute of Child Health),Ìý
  • Professor Alan Salama (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳),Ìý
  • Professor Reza Motallebzadeh (Department of Renal Medicine, ×î×¼µÄÁùºÏ²ÊÂÛ̳, Research Dept of Surgical Biotechnology, ×î×¼µÄÁùºÏ²ÊÂÛ̳ & Institute of Immunity and Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)

Engineered Tissues

Human kidney extracellular matrix hydrogels as a natural 3D platform for bioengineered models of kidney fibrosis

The aim is to develop, characterize, and validate a novel in vitro 3D human kidney organoid culture system ultimately aimed at screening for compounds capable of modulating the tubulointerstitial microenvironment crosstalk that perpetuates the development of fibrosis in chronic kidney disease.

Collaborators

  • Professor Reza Motallebzadeh
  • Professor Jill Norman (×î×¼µÄÁùºÏ²ÊÂÛ̳ Centre for Experimental Nephrology)
  • Professor Krista Rombouts (×î×¼µÄÁùºÏ²ÊÂÛ̳ Institute for Liver and Digestive Health)
  • Dr Giuseppe Mazza (Engitix Therapeutics)
  • Dr Breda Twomey (UCB Pharma)

Outcomes ResearchÌý

Qualitative assessment of the impact of human cytomegalovirus infection in kidney transplant recipients

Cytomegalovirus (CMV) is a common global viral infection; it can remain inactive following an initial infection but then can be reactivated post-transplantation or can be transmitted from the transplanted organ, both causing major problems and disease in kidney transplant recipients on immunosuppression treatment. The severity may lead to failure of the kidney transplant or in some cases death. We know from patients that they worry about the risk of this frequent complication after a kidney transplant. We will be conducting a qualitative study to understand how CMV infection after kidney transplantation impacts patient health, determine what is the impact on their quality of life, and to what degree do the usual symptoms of CMV infection, such as reduced physical activity and mobility as well as mental fatigue and stress, affect their daily lifestyle.

Collaborators

  • Professor Reza Motallebzadeh
  • Professor Prof Cecilia Vindrola (Department of Targeted Intervention, ×î×¼µÄÁùºÏ²ÊÂÛ̳ Division of Surgery & Interventional Sciences)
  • Dr Tanzina Haque (Royal Free London NHS Foundation Trust)
  • Dr Matthew Reeves (Institute of Immunity & Transplantation, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
Investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children

This study investigates which factors are important and potentially modifiable to improve access to kidney transplantation and transplant outcome measures, funded by National Institute of Health and Care Research.

Collaborators

  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • British Association for Paediatric Nephrology,
  • UK Kidney AssociationÌý
  • National Health Service Blood and Transplant
A prospective longitudinal multi-centre study evaluating modifiable barriers to accessing transplantation and transplant outcomes in children, in Europe

This study, called European Paediatric Access to Kidney Transplantation (EuPAKT) looks at the infrastructure of non-transplant and transplant paediatric nephrology centres in Europe, funded by the European Society for Paediatric Nephrology.
Ìý
Collaborators

  • Professor Stephen Marks (GOS Institute of Child Health, ×î×¼µÄÁùºÏ²ÊÂÛ̳)
  • European Society for Paediatric Nephrology and CERTAIN (Cooperative European Paediatric Renal TransplAntINitiative)

Clinical Trials

Surveillance of arteriovenous fistulae using ultrasound (SONAR study)

A prospective multi-centre observational cohort study to determine whether ultrasound surveillance can reliably predict arteriovenous fistulae failure in patients with chronic kidney disease.

Anaesthesia Choice for Creation of Arteriovenous Fistulae (ACCESs study)

A randomised controlled trial comparing clinical (one-year functional patency rate) and cost-effectiveness of regional versus local anaesthesia for primary arteriovenous fistula formation.

Pre-Implantation trial of Histopathology In renal Allografts (PITHIA study)

An open, stepped-wedge cluster, randomised trial to determine if the introduction of a national pre-implantation biopsy histopathology service increases numbers, and improve outcomes, of kidney transplants performed in the UK.

Cardiorespiratory Optimisation By AVF Ligation after Transplantation (COBALT study)

Should we ligate haemodialysis fistulas in patients once they have been transplanted successfully? This feasibility study aims to objectively detail how arteriovenous fistula (AVF) disconnection in renal transplant recipients can change cardiorespiratory fitness and physical capacity, thereby potentially increasing patients' activity levels and improving quality of life.

PlasmaLyte Usage and assessment of kidney Transplant Outcomes in children: the PLUTO trial

A randomised controlled open-label trial comparing PlasmaLyte to standard intravenous fluid in paediatric kidney transplant recipients.

Safety and tolerability study of chimeric antigen receptor T-Reg cell therapy in living donor renal transplant recipients (STreadfast)

A Multicentre, Open-Label, Single Ascending Dose, Dose Ranging, Phase I/IIa Study to Evaluate the Safety and Tolerability of an Autologous Antigen-Specific Chimeric Antigen Receptor T Regulatory Cell Therapy (TX200-TR101) in Living Donor Renal Transplant Recipients.

Canadian-Australasian Randomised Trial of Screening Kidney Transplant Candidates For Coronary Artery Disease (CARSK study)

A multicentre, non-inferiority, two-parallel-arm randomised trial of cardiac screening in adults with chronic kidney disease who are awaiting kidney transplant.

KIDNEY BEAMS-KIDS platform for paediatric kidney transplant recipients: a feasibility study

Co-design, development and evaluation.

Our experts

Reza Motallebzadeh

(co-lead)

Professor Stephen Marks

Ìý(co-lead)

Dr Rhys Evans

Ìý(co-lead)

Daniyal Jafree

(ECR, co-lead)

Professor Alan Salama

David Long

Dr Mark Harber

Gareth Jones

Dr Gareth Jones

Professor John Cunningham

Peter Dupont

Dr Peter Dupont

Prodromos Laftsidis

Mr Prodromos Laftsidis

Colin Forman

Mr Colin Forman

Ayaz Hossain

Fiona McCaig

Miss Fiona McCaig

Ammar Al-Midani

Professor Julian Gillmore

Inji Alshaer

Philip Masson

Dr Phil Masson

Kin-Yee Shiu

Dr Kin Yee Shiu

Basic silhouette in a circle, in light grey

Dr Ray Fernando

Dr Raymond Fernando

Ìý

Group members

  • Dr Amber Gintare Vaitkute - Post-doctoral research fellow (2020)
  • Ìý- PhD Student (2020)
  • - PhD Student (2020)
  • - PhD student (2020)
  • Dr Heidy Hendra - PhD student (2022)
  • - NIHR Advanced Research Fellow / Lecturer in Dietetics
  • Dr Nikolaos Salaris PhDÌý- Post-doctoral research fellow (2022)

Selected Publications

  1. SurendrakumarÌýV, Aitken E, MarkÌýP, MotallebzadehÌýRÌý... GarbiÌýMÌý(2023). . BMJ Open, 13 (2).
  2. ForrestÌýC, ChaseÌýT, CuffÌýA, MaroulisÌýD, MotallebzadehÌýR, GanderÌýAÌý... ReevesÌýMÌý(2023). . Nature Communications 14, 1409.
  3. FabesÌýJ, WittenbergÌýM, MotallebzadehÌýRÌý(2022). Anaesthetic considerations and post-operative care of living kidney donors. In LipkinÌýG, SharifÌýAÌý(eds.), Living Kidney Donation - A Practical Guide. Springer Nature.
  4. GreenhallÌýG, Ushiro-LumbÌýIÌý... JonesÌýG, MotallebzadehÌýR, ArslanÌýZ, MarksÌýSD, et alÌý(2022). . Transplantation, Sept. 1;106(9), 1824-1830.
  5. MotallebzadehÌýRÌý(2022). Minimisation of Immunosuppression - Time for Precision Medicine in Kidney Transplantation
  6. AshbyÌýDR, CaplinÌýB, CorbettÌýRW, AsgariÌýE, KumarÌýN, Sarnowski AÌý...ÌýChenÌýJÌý(2022). .ÌýNephrology Dialysis Transplantation, gfac209.
  1. ManookÌýM, MotallebzadehÌýR, PettigrewÌýGJÌý(2022). . Science Translational Medicine, 14 (663).
  2. EvansÌýRDR, et alÌý(2022).Ìý Clin. J. Am. Soc. Nephrol. CJASN 17, 271-279.
  3. AshbyÌýDR, CaplinÌýB, CorbettÌýRW, AsgariÌýEÌý... ChenÌýJÌý(2022). .ÌýClin J Am Soc Nephrol.
  4. JafreeÌýD, StewartÌýB, Kolatsi-JoannouÌýM, DavisÌýB, MitchellÌýH, RussellÌýLG, Marinas del ReyÌýLÌý... MotallebzadehÌýR, et alÌý(2022). .
  5. MacfarlaneÌýAJR, KearnsÌýRJ, ClancyÌýMJ ... Vindrola-PadrosÌýCÌý(2021). . BMJ Open, 11 (12).
  6. JafreeÌýD, Kolatsi-JoannouÌýM, StewartÌýB, PomeranzÌýG, Marinas Del ReyÌýLÌý... ScamblerÌýPÌý(2021). Interrogating the spatial and molecular profile of kidney lymphatic vessels in health and transplant rejection.

Paediatric Renal Transplantation

  1. Hew EY, Kessaris N, Stojanovic J ... Marks SD (2023).Ìý.ÌýPediatr Nephrol 2023; 28(2): 529-535.
  2. Laroche C, Marks SD (2023). .ÌýPediatr Transplant 2023; e14533.
  3. Plumb L, Marks SD (2023). .ÌýPediatr Nephrol 2023; 38(4): 941-944.
  4. Smith J, Marks SDÌý(2023). .ÌýPediatr Transplant 2023; Suppl 1: e14384.
  5. Wray J, Kim JS, Marks SDÌý(2023). .ÌýPediatr Transplant 2023; Suppl 1: e14337.
  6. Papadakis G, Kallath S, Marks SD, Callaghan CÌý(2023).Ìý.ÌýPediatr Transplant 2023; Suppl 1: e14423.
  7. Raina R, Shah R, Marks SD, et alÌý(2023). .ÌýPediatr Transplant 2023; e14490.
  1. Preiksaitis J, Allen U, Bollard CM, Dharnidharka VE ...ÌýMarks SD, et al (2023). .ÌýPediatr Transplant 2023; e14471.
  2. Kim JJ, Curtis RMK, Reynolds B, Marks SDÌýet alÌý(2023). .ÌýFront Pediatr 2023; 14: 1207145.
  3. Hernandez-Benabe S, Batsis I, Dipchand AI, Marks SDÌýet al (2023). s.ÌýPediatr Transplant 2023; Suppl 1: e14317.
  4. Matsuda-Abedini M, Marks SD, Foster BJ (2023).Ìý.ÌýPediatr Nephrol 2023; 38(2): 383-390.
  5. Mudalige NL, Callaghan CJ, Marks SD (2022). . Transplantation 2022; 106(3): 453-454.
  6. Patel R, Withers C, Bamford A, Marks SD (2022).Ìý.ÌýPediatr Transplant 2022; 26(7): e14336.

Funding and PartnershipsÌýÌý

NIH in white on a grey background, with a pointed edge to the right indicating an arrow

NIHR ×î×¼µÄÁùºÏ²ÊÂÛ̳H comprehensive biomedical research centre logo

Kidney Reseach UK logo

A logo featuring a styled RT containing a rose. Text reads: "Rosetrees Trust. Supporting the best in medical research"

Great Ormond Street Hospital Biomedical Research Centre logo

Royal Free Charity logo

UCB Pharma logo

×î×¼µÄÁùºÏ²ÊÂÛ̳ Healthcare Engineering logo

NHS Blood and Transfusion logo

European Society of Paediatric Nephrology logo

Great Ormond Street Hospital Charity logo

Ìý

Related programmes

Our members contribute to the MBBSÌýand master's degrees within the Division of Medicine. We provide BSc and MSc/MRes research project supervision. We also have an established track record in providing high-quality training to PhD students interested in basic, translational, and clinical research in the areas of transplantation. Our teaching involvementÌýincludes the following.

Contact details

Charity

If you are interested in supporting our research programme, please contact:

Kate Henderson (kate.henderson@ucl.ac.uk)

Media coverage

Eight-year-old Aditi Shankar playing with a toy in hospital

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A screenshot of Reza Motallebzadeh interviewed on BBC London news
  • Prof. Reza Motallebzadeh interviewed on BBC London news in 2021

Research activity

Poster for Living Kidney Donation and Transplantation in Jain and Hindu Communities, with list of speakers. 26 February 2023
  • Living Kidney Donation and Transplantation Poster (February 2023)

Professor Reza Motallebzadeh and group members below the stage at the Edinburgh Joint Congress 2023
  • Group members attend the Edinburgh Joint CongressÌý2023