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Understanding the immune mechanisms underlying development of allograft vasculopathy and chronic rejection in solid organ transplantation.
Centre Lead - Professor Reza Motallebzadeh
Areas of Focus
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.
My laboratory is focused 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. My research primarily focuses on understanding mechanisms of allograft failure and improving long-term graft and patient survival outcomes in renal transplantation.
- Delineating the role of the host microbiota in renal transplantation
- Developing 3D renal organoids to study renal fibrosis
- Study of B cell responses to SARS-CoV-2 vaccination in end-stage kidney disease and defining the basis of a hyporesponsive immune phenotype
- Trial of biomarker-guided minimization of immunosuppression therapy in elderly renal transplant recipients
Description of Research
Basic Science & Translational
- Integrating immunological, metabolite and microbiome data to predict clinical outcomes in kidney transplantation.
Collaborators – Dr Bajaj-Elliot (GOS Institute of Child Heath, UCL), Dr Pesenacker (Institute of Immunity & Transplantation, UCL), Dr Jonathan Swann (Division of Integrative Systems Medicine and Digestive Diseases, Imperial College London), Dr Mark Harber, Professor Alan Salama & Dr Jennifer Rohn (Department of Renal Medicine, UCL)
Outline - 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.
- Development of a point-of-care assay for monitoring rejection after renal transplantation.
Collaborators – Professor Tiwari & Professor Balabani (Dept of Mechanical Engineering, UCL), Dr Mark Harber (Department of Renal Medicine, UCL)
Outline – Development of 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.
- Human kidney extracellular matrix hydogels as a natural 3D platform for bioengineered models of kidney fibrosis
Collaborators - Proessor Norman (UCL Centre for Experimental Nephrology), Dr Mazza (Institute of Liver & Digestive Health), Dr Twomey (UCB Pharma)
Outline - The aim of this work 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 development of fibrosis in chronic kidney disease.
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.
https://www.nhsbt.nhs.uk/clinical-trials-unit/current-trials-and-studies...
- Should we ligate haemodialysis fistulas in patients once they have been transplanted successfully? A feasibility study. (Study acronym-COBALT; Cardiorespiratory Optimisation By AVF Ligation after Transplantation)
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.
ISRCTN49033491 https://doi.org/10.1186/ISRCTN49033491
Group members
 | Dr Amber Gintare Vaitkute – Post-doctoral research fellow (2020)
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 | Fernando Yuen Chang – PhD Student (2020)
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 | Lucia Marinas del Rey – PhD Student (2020)
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 | Dr Arnab Guha - Post-doctoral research fellow (2021)
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Faculty
- Centre Lead: Reza Motallebzadeh
- Deputy Lead: Rhys Evans
- Neal Banga
- Ben Caplin
- John Cunningham
- Peter Dupont
- Bimbi Fernando
- Colin Forman
- Julian Gillmore
- Mark Harber
- Gareth Jones
- Stephen Marks
- Phil Masson
- Kin Yee Shiu
- Henry Stephens