Overview
Lupus nephritis
Systemic lupus erythematosus is a multisystem autoimmune disease most commonly occurring in women of child bearing age and in women of colour. About 40-60% will develop lupus nephritis ((LN) inflammation due to lupus in their kidneys) and a significant proportion of these patients will go on to end stage kidney disease (ESKD) despite optimal current treatment. Treatment regimens have included high dose steroids since 1950, now well recognised for causing long term damage to patients.
Through funding from MRC, Arthritis ResearchUK, NIHR, Lupus UK and Roche (~£5million since 2013), my LN research has focused on developing better diagnostic and prognostic tools and transforming therapeutic approaches. With my colleagues at Imperial we were the first to show that rituximab was steroid-sparing in LN, and in a paradigm shift, that LN could be treated without oral steroids1. Our work led to steroid minimisation becoming a goal in all LN trials and accepted as a part of the definition of remission in SLE and LN. We demonstrated that low hydroxychloroquine levels ‘captured’ non-adherence and higher risk of LN flare2. We identified that having ANCA leads to worse prognosis in LN3 and continue to evaluate new therapeutic targets e.g complement. By helping design, monitor and analyse several global clinical studies, writing EU & UK guidelines, developing a Glucocorticoid Toxicity Index4, been the UKKA clinical expert on several NICE STAs of new drugs for LN, advised the EMA, my impact in LN is global. My influence in glomerular disease more generally is evident from my role as Co-Chair of the SONG-GD International Steering Group, which is defining core outcomes5, agreed by patients and health professionals, for GD trials and ensuring the patient voice is at the centre of kidney research6.
https://songinitiative.org/projects/song-gd/
Pregnancy in women with kidney disease
Recognizing the challenges faced by women with chronic kidney disease (CKD) who wish to have children, I established, and was the first national coordinator of, the National Rare Renal Chronic Kidney Disease (CKD) & Pregnancy Registry, which will define outcomes and unmet need. I promoted steroid avoidance in LN in pregnancy and showed tacrolimus is safe in breastfeeding. Having identified biomarkers that distinguish pre-eclampsia from CKD, defined normal renal function in pregnancy and developed a personalized pregnancy risk assessment for women with CKD7 (featured in an NIHR alert), I helped establish an international network to predict pregnancy’s impact on kidney function. I was the renal expert on the NICE guideline “Intrapartum Care of Women with Pre-existing Medical Conditions” (NG121) and am coauthor of the Renal Association Guideline on Renal Disease and Pregnancy8, which is NICE assured and the first of its kind.
https://ukkidney.org/rare-renal/patient/pregnancy-and-chronic-kidney-disease-0
COVID-19 and immunocompromised patients
During the COVID-19 pandemic I have led on treatment guidance for immunosuppressed kidney patients nationally and all patients with severe COVID in the Trust; I am a core member of the Renal COVID research group led by Dr Michelle Willicombe, focused on understanding the impact of immunosuppression on COVID-19 infections and responses to vaccines. Our work9,10 has contributed to JCVI decisions including 3rd vaccine doses for vulnerable patients. We are now leading the UKRI-MRC funded, CUE-TIP prioritised MELODY study, evaluating responses to 3rd / 4th COVID vaccines in nearly 30,000 immunocompromised patients with solid organ transplants, or with blood cancer or with rare autoimmune diseases who have been treated with rituximab (mostly those with vasculitis / lupus).
https://www.imperial.ac.uk/medicine/research-and-impact/groups/melody-study/
Key publications
Lupus nephritis – key papers
- Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013; 72:1280-6.
- Turner-Stokes T, Wilson H, Morreale M, Nunes A, Cairns T, Cook T, Pusey C, Tarzi R, Lightstone L Positive ANCA serology in patients with lupus nephritis is associated with distinct histopathological features on renal biopsy Kidney Int 2017; 92:1223-1231 (associated Commentary same issue p1048-1050);
- Cunha C, Alexander S, Ashby D, Lee J, Chusney G, Cairns TD, Lightstone L. Hydroxychloroquine blood concentration in lupus nephritis: a determinant of disease outcome? Nephrol Dial Transplant 2018; 33:1604-1610
- Miloslavsky EM, Naden RP, Bijlsma JWJ, Brogan PA, Sherwood Brown E, Brunetta P, Buttgereit F, Choi HK, DiCaire J-F, Gelfand JM, Heaney LG, Lightstone L, Lu N, Murrell DF, Petri M, Rosenbaum JT, Saag KS, Urowitz MB, Winthrop KL, Stone JH. Development of a glucocorticoid toxicity index (GTI) using multicriteria decision analysis. Ann Rheum Dis 2017; 76:543-546
- Carter SA, Lightstone L, Cattran D, Bagga A et al Standardised outcomes in Nephrology-Glomerular disease (SONG-GD): establishing a core outcome set for trials in patients with glomerular disease Kidney Int 2019; 95:1280-83
- Tong A, Levey AS, Eckardt KU, Anumudu S, Arce DM, Baumgart A, Dunn L, Gutman T, Harris T, Lightstone L, et al Patient and caregiver perspectives on terms used to describe kidney health Clin J Am Soc Nephrol 2020; 15:937-948
Pregnancy in women with kidney disease – key papers
7. Wiles K, Webster P, Seed PT, Bennett-Richards K, Bramham K, Brunskill N, Carr S, Hall M, Khan R, Nelson-Piercy C, Webster LM, Chappell LC & Lightstone L. The Impact of Chronic Kidney Disease Stages 3-5 on Pregnancy Outcomes. Nephrol Dial Transplant 2020 Dec 12 doi:10.1093/ndt/gfaa247 Online ahead of print. PMID:33313680 (Featured in NIHR Alert - https://evidence.nihr.ac.uk/alert/women-kidney-disease-given-risk-assessment-pregnancy/)
8. Wiles K, Chappell L, Clark K, Elman L, Hall M, Lightstone L, Mohammed G, Mukherjee D, Nelson-Piercy C, Webster P, Whybrow R and Bramham K; Renal Association Clinical Practice Guideline (NICE accredited): Pregnancy and Renal Disease 2019 https://renal.org/wp-content/uploads/2019/09/FINAL-Pregnancy-Guideline-September-2019.pdf and Clinical practice guideline on pregnancy and renal disease BMC Nephrol 2019; 20:401-44
SARS-COV-2 and immunosuppressed – key papers
9. Prendecki M, Thomson T, Clarke CL, Martin P, Gleeson S, Cardoso de Aguiar R, Edwards H, Mortimer P, McIntyre S, Mokreri D, Cox A, Pickard G, Lightstone L, Thomas D, McAdoo SP, Keller P, Willicombe M, and the Imperial Renal COVID-19 vaccine study group in collaboration with the OCTAVE Study Consortium. Immunological responses to SARS-COV-2 vaccines in kidney transplant recipients Lancet 2021; 398:1482-1484
10. Prendecki M, Clarke C, Edwards H, McIntyre S, Mortimer P, Gleeson S, Martin P, Thomson T, Randell P, Shah A, Singanayagam A, Lightstone L, Cox A, Kelleher P, Willicombe M and McAdoo S Humoral and T cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression Ann Rheum Dis 2021; 80:1322-1329
Collaborators
Dr Frederic Houssiau, Chief Investigator, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Bruxelles,Belgium, Chair, Data Safety Monitoring Committee, RING Trial - Rituximab for Lupus Nephritis with Remission as a Goal, 2013
Brad H. Rovin, MD, FACP, FASNProfessor of Medicine and PathologyVice Chairman of Research for Internal MedicineDirector, Division of Nephrology, The Ohio State University College of Medicine, Lupus nephritisCollaborator on biomarkers in lupus nephritisUS lead in Rituxilup trial, 2012
Professor Ronald van Vollenhoven, Unit for Clinical Therapy Research, Inflammatory Diseases (Clin TRID), Department of Medicine, Karolinska Institute, Stockholm, Sweden, Collaborating on RITUXILUP trial in lupus nephritis - I am chief investigator of the international multicentre randomised controlled trial and he is the lead for the non UK EU sites., 2011
Dr Giovanna Lombardi, Guy's, Kings and St Thomas' Medical School, 2005 - 2008
Dr Paul Roderick and Dr Mark Mullee, Medical Epidemiology Unit, Southampton University, 2003
Dr Marta Lapsley and Dr Mark Dockrell, South West Thames Renal Research Institute, 2003
Mr Gurch Randhawa, Luton University, 2002
Guest Lectures
Lupus nephritis: updates in diagnosis and treatment - calcineurin inhibitors and more, American College of Rheumatology Annual Meeting, Online, 2020
Pregnancy and lupus nephritis, American Society of Nephrology, Online, 2020
Managing lupus nephritis in the 21st century, Fertility and pregnancy issues in patients with lupus nephritis. Case study interactive workshop, Lupus Academy, 2020
Addressing the challenges posed by pregnancy in CKD, ERA-EDTA 2020 - Gold Plenary, Online, 2020
Lupus nephritis presenting in pregnancy (cancelled because of COVID), World Congress of Nephrology, Abu Dhabi, UAE, 2020
TED Talk - steroid free remission in lupus nephritis, American College of Rheumatology Annual Meeting, Atlanta, GA, USA, 2019
Managing glomerulonephritis during pregnancy, American Society of Nephrology Kidney Week, Washington DC, USA, 2019
Invited speaker and roundtable discussant, Israel Society of Rheumatology, 2019
Update on the treatment of lupus nephritis, EULAR Congress 2019, Madrig, 2019
Balancing risk - what to advise when it's all going very badly, UK Kidney Week 2019, Brighton, 2019
1. Vasculitis: what makes the diagnosis?2. Are MAbs the holy grail for the treatment of lupus nephritis3. Withdrawing immunosuppression in lupus4. Recent developments in the treatment of adult nephrotic syndrome, ApEx CS 2019 Board Review Course Mumbai, Mumbai, India, 2019
Pregnancy in lupus and other autoimmune diseases, World Congress of Nephrology, Melbourne, Australia, 2019
Frontiers in Glomerulonephritis - What's new in lupus nephritis?, Royal Society of Medicine, London, 2019
Novel approaches to define patients with lupus nephritis at high risk of poor outcomes, 10th European Lupus Meeting,, Venice, Italy, 2016
SLE in pregnancy, IMSANZ and SOMANZ Combined Annual Meeting, Alice Springs, Australia, 2016
Chandos lecture "Pregnancy and kidney disease", UK Kidney Week, Birmingham, UK, 2016
Mono- versus add-on anti-CD20 therapy in lupus nephritis, ISN Nexus Symposium 2016, Berlin, Germany, 2016
Meet the Professor Session, American College of Rheumatology Annual Meeting, San Francisco, 2015
SLE and pregnancy: concerns and management, American Society of Nephrology Annual Meeting, San Diego, 2015
Diagnosis and therapy: to Bx or not to Bx and to Cx or not to Cx? Ideas about GC-free remission, 11th International Congress on Systemic Lupus Erythematosus, Vienna, 2015
Meet the Professor sessions on lupus nephritis 2014-2016, American College of Rheumatology, Annual meeting, San Francisco, USA, 2014
Do we really need steroids to treat lupus nephritis?, Gerald Loewi Rheumatology Meeting, Israel, 2014
Glucocorticoid-free treatment for lupus nephritis - a paradigm shift in the making?, 3rd Lupus Academy Meeting, Berlin, 2014
Lupus nephritis - Retreat from Steroids, Ten Topics 2013 - rheumatology meeting held at St Thomas' Hospital. International meeting. Audience of about 150, St Thomas' Hospital, 2013
Use of Biologics in the treatment of Lupus NephritisPlenary lecture, 10th Lupus World Congress in Buenos AiresPlenary session - audience 1500, Hilton, Buenos Aires., 2013
Meet the Professor - Management of Lupus Nephritis, at the 10th Lupus World Congress in Buenos Aires, Hilton, Buenos Aires, 2013
Guest lecture - Up to date: Lupus biopsy - the nephrologist's point of view. Audience ~400, 10th Lupus World Congress Buenos Aires, Hilton, Buenos Aires., 2013
Lupus nephritis - update on modern management, 2nd Lupus Academy - The Lupus Academy* is a long term global educational initiative lead by a Steering Committee of international experts in Lupus, who endeavour to provide unparalleled scientific and clinical updates in Lupus, through highly interactive annual meetings and associated enduring learning materials. We believe the Lupus Academy stimulates our members with new ideas and enhanced enthusiasm for future interaction and discussion with their colleagues in Lupus. I was invited back after the meeting in Barcelona and again was the only nephrologist on the Faculty., Held as part of Lupus 2013 - 10th International Congress on SLE, 2013
How I treat difficult lupus, Joint Renal Association / British transplant Society Meeting March 2013, Bournemouth, 2013
Plenary lecture: 1. Can we avoid end-stage renal disease in all patients? (with lupus nephritis)Workshop: Lupus Kidney Disease - when to biopsy? How to treat, The Lupus Academy is a long-term initiative committed to improving patient outcomes in SLE and allied diseases. By providing a highly interactive educational forum, the Lupus Academy is dedicated to sharing best clinical practice through the dissemination and discussion of cutting edge scientific and clinical research. The first meeting was held in Barcelona in 2012. I was the only nephrologist on the faculty and received the highest rating of any speaker for both my plenary lecture and the workshops I ran., Fire Palace Hotel, Barcelona, Spain, 2012
Look: No Steroids!, Ten Topics in Rheumatology, St Thomas' Hospital, 2011
Managing difficult organ involvement in SLE - The Kidney, 8th European Lupus Meeting, Porto, Portugal, 2011
Plenary talk - Current Topics in Lupus Nephritis, Lupus Nephritis Conference, Kyorin University,, Tokyo, Japan, 2010
Identifying Novel Biomarkers of Disease Activity in Lupus Nephritis, EULAR (European League Against Rheumatism) 2009, Copenhagen, Denmark, 2009
Modern Management of Lupus Nephritis, Chung Shan Medical University, Taichung, Taiwan, 2008
Preconception advice for women with renal disease, EDTA-ERA annual meeting, Stockholm, 2008
Biomarkers in Lupus Nephritis, Oxford Renal Unit, Churchill Hospital, Oxford, 2008
Treating Lupus Nephritis without oral steroids, Roche Headquarters, Welwyn Garden City, Herts, 2008
Pregnancy and Diabetic nephropathy, Pregnancy and Diabetes Study Day, Queen Charlotte's and Imperial College London, The Royal Brompton Hospital, London, 2007
Managing Renal Disease in Pregnancy, Medical Complications in pregnancy, Imperial College London And RCP London, RCP London, 2007
The Kidney in Rheumatic Disease, Royal College Physicians, London, London, 2007
Renal disease in UK ethnic communities, World Congress of Nephrology, Rio De Janeiro, 2007
Renal disease in UK migrant communities, Renal Disease in Developing Countries, Satellite symposium of World Congress of Nephrology, Rio de Janeiro, Brazil, 2007
Lessons from Lolipop, St George's Hospital Renal Unit, St George's Hospital, London, 2007
Treating Lupus nephritis without oral steroids, Rituximab Workshop, St Olaf House, London, 2006
The West London Project (ABLE) project, ABLE Project update, NKRF, Salter's Hall, London, 2004
Renal Disease and Pregnancy, Manchester Renal Unit, Manchester Royal Infirmary, 2004
Chair, West London and Imperial Renal Research Forum, 2004
Renal Disease and Ethnicity, Half day meeting on prevention of CKD, Jermyn Str, London, 2004
Renal Disease in Ethnic Patients, Postgraduate Seminar Rooms, Charing Cross Hospital, 2004
How to Manage Renal Disease in Pregnancy, Advanced Medicine Conference, Royal College of Physicians, 2004
Prevention of Renal Failure in the Ethnic Minority Population, Royal College of Physicians, 2004
Symptoms, Signs and Tests in Renal Medicine, Kigezi International School of Medicine, Cambridge, 2004
Effects of Therapy of Autoimmune Disease on Fertility and Pregnancy, Royal Society of Medicine, 2004
Managing Renal Disease in Pregnancy, Imperial College/Hammersmith Hospital Short Course, 2003
The Management of a Pregnant Patient with pre Existing Chronic Renal Disease, University of Birmingham, Birmingham, 2003
Management of SLE, Northern Deanery SpR Training Day (Leeds), 2003
Delivering Culturally Sensitive Renal Services, Health Care Events, RCS, 2003
ABLE and Beyond, Hammersmith Hospital Kidney Patients' Association, 2003
Renal Disease in Pregnancy, Theory of Obstetric Medicine, RCP, 2003
Renal Disease in Ethnic Communities, Postgraduate Centre, Ealing Hospital, 2003
Renal Disease and Ethnic Communities, Postgraduate Centre, Mount Vernon Hospital, 2003
Renal Disease in Pregnancy, Renal Unit, University of Birmingham, 2003
The Ethnic Challenge: Preventing Kidney Disease, Renal Disease in Ethnic Communities - Disparity or Diversity? South West Thames Institute, 2003
Symptoms, signs and tests in Renal Disease, Kigezi International School of Medicine, Cambridge, 2003