ProfessorLiz Lightstone
Professor of Renal Medicine
Department of Immunology and Inflammation - Faculty of Medicine
Orcid identifier0000-0002-4603-4076 (opens in a new tab)
- Professor of Renal MedicineDepartment of Immunology and Inflammation - Faculty of Medicine
- 0207 594 3703 (Work)
- Commonwealth Building, Hammersmith Campus, United Kingdom
RESEARCH
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.
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.
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).
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 - )
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 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
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.
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.
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).
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 - )
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 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