Publications
226 results found
Gilmore A, Wilson H, Cairns T, et al., 2022, Immune gene expression and functional networks in distinct lupus nephritis classes, Lupus Science & Medicine, Vol: 9, ISSN: 2053-8790
Objective: To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods: Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane disease (TBM, n=14) and membranous nephropathy (MN, n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms. Results: In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN. Conclusion: Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.
Greenhalgh T, Griffin S, Gurdasani D, et al., 2022, Covid-19: An urgent call for global "vaccines-plus" action, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X
- Author Web Link
- Cite
- Citations: 15
Carter SA, Teng C, Gutman T, et al., 2022, A Focus Group Study of Self-Management in Patients With Glomerular Disease, KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 56-67, ISSN: 2468-0249
- Author Web Link
- Cite
- Citations: 2
Podos S, Nester C, Appel G, et al., 2022, Clinical and biomarker characteristics of patients with C3G enrolled in two phase II studies investigating the factor D inhibitor danicopan, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 148-148, ISSN: 0161-5890
Carter SA, Lightstone L, Cattran D, et al., 2022, A Core Outcome Set for Trials in Glomerular Disease A Report of the Standardized Outcomes in Nephrology?Glomerular Disease (SONG-GD) Stakeholder Workshops, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 17, Pages: 53-64, ISSN: 1555-9041
- Author Web Link
- Cite
- Citations: 1
Shipa M, Embleton-Thirsk A, Parvaz M, et al., 2021, Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus A Randomized Controlled Trial, ANNALS OF INTERNAL MEDICINE, Vol: 174, Pages: 1647-+, ISSN: 0003-4819
- Author Web Link
- Cite
- Citations: 42
Wiles K, Webster P, Seed PT, et al., 2021, The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes, NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol: 36, Pages: 2008-2017, ISSN: 0931-0509
- Author Web Link
- Cite
- Citations: 30
Prendecki M, Thomson T, Clarke CL, et al., 2021, responses to SARS-CoV-2 vaccines in kidney transplant recipients, LANCET, Vol: 398, Pages: 1482-1484, ISSN: 0140-6736
- Author Web Link
- Cite
- Citations: 45
Evans RA, McAuley H, Harrison EM, et al., 2021, Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study, The Lancet Respiratory Medicine, Vol: 9, Pages: 1275-1287, ISSN: 2213-2600
BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health bur
Carter SA, Logeman C, Howell M, et al., 2021, Development of an international Delphi survey to establish core outcome domains for trials in adults with glomerular disease, KIDNEY INTERNATIONAL, Vol: 100, Pages: 881-893, ISSN: 0085-2538
- Author Web Link
- Cite
- Citations: 3
Furie R, Houssiau F, Lightstone L, et al., 2021, Belimumab Improves Renal Responses in Patients with or Without Steroid Pulses During Induction Therapy for Lupus Nephritis, Publisher: WILEY, Pages: 3068-3070, ISSN: 2326-5191
Prendecki M, Clarke C, Edwards H, et al., 2021, Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression., Annals of the Rheumatic Diseases, Vol: 80, Pages: 1322-1329, ISSN: 0003-4967
OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.
Davies JC, Carlsson E, Midgley A, et al., 2021, A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment., Rheumatology (Oxford), Vol: 60, Pages: 3747-3759
OBJECTIVES: ∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE. METHODS: A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment. RESULTS: Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818). CONCLUSIONS: Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.
Ralston E, Bramham K, Clery A, et al., 2021, Pregnancy-associated progression of chronic kidney disease: development of a clinical predictive tool, Publisher: WILEY, Pages: E36-E36, ISSN: 1470-0328
Clarke CL, Prendecki M, Dhutia A, et al., 2021, Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection, Kidney International, Vol: 99, Pages: 1470-1477, ISSN: 0085-2538
Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.
Wiles K, Bramham K, Seed PT, et al., 2021, Placental and endothelial biomarkers for the prediction of superimposed pre-eclampsia in chronic kidney disease, PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH, Vol: 24, Pages: 58-64, ISSN: 2210-7789
- Author Web Link
- Cite
- Citations: 5
Satta G, Youngstein T, Lightstone L, et al., 2021, The utility of a local multidisciplinary working group to oversee the establishment of rapidly evolving standards of care and to support trial recruitment during the COVID-19 pandemic, Clinical medicine (London, England), Vol: 21, Pages: e287-e289, ISSN: 1470-2118
Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China. The first analyses of cases described high numbers of critically ill patients requiring intensive care admission with significant late inflammatory features. By the time the first cases of SARS-CoV-2 infection were diagnosed in the UK, a wide range of drugs were under consideration and it became clear that the input of clinicians covering all organ systems (in particular, infectious diseases, haematology, rheumatology, renal medicine and intensive care) and of expert specialist pharmacists was necessary at the local level. Thus, an expert multidisciplinary (MDT) group within our organisation was convened to offer a standardised approach and robust clinical governance for the treatment of COVID-19 patients admitted to our hospitals and rapidly develop standards of care as evidence evolved. This commentary explores the methods and mechanisms for creating an MDT COVID-19 treatment working group which are applicable to any hospital likely to admit and care for high numbers of COVID-19 patients and demonstrates how the structure and governance of the group allowed for rapid adoption of both dexamethasone and tocilizumab into standard of care as data became available.
Gleeson S, Martin P, Bedi R, et al., 2021, Answering the call to action: rapid implementation of an in-center hemodialysis SARS-CoV-2 vaccination program, Kidney International, Vol: 99, Pages: 1238-1239, ISSN: 0085-2538
Nester C, Podos S, Hogan J, et al., 2021, CLINICAL AND BIOMARKER CHARACTERISTICS OF PATIENTS WITH C3G OR IC-MPGN ENROLLED IN TWO PHASE II STUDIES INVESTIGATING THE FACTOR D INHIBITOR DANICOPAN, 58th Congress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA), Publisher: OXFORD UNIV PRESS, Pages: 149-149, ISSN: 0931-0509
- Author Web Link
- Cite
- Citations: 2
Turner-Stokes T, Jiang E, Johnson N, et al., 2021, Serological screening for COVID-19 in patients with glomerular disease, Kidney International Reports, Vol: 6, Pages: 1402-1406, ISSN: 2468-0249
Medjeral-Thomas N, Troldborg A, Hansen A, et al., 2021, Plasma lectin pathway complement proteins in patients with COVID-19 and renal disease, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224
We do not understand why non-white ethnicity and chronic kidney disease increase susceptibility to COVID-19. The lectin pathway of complement activation is a key contributor to innate immunity and inflammation. Concentrations of plasma lectin pathway proteins influence pathway activity and vary with ethnicity. We measured circulating lectin proteins in a multi-ethnic cohort of chronic kidney disease patients with and without COVID19 infection to determine if lectin pathway activation was contributing to COVID19 severity.We measured 11 lectin proteins in serial samples from a cohort of 33 patients with chronic kidney impairment and COVID19. Controls were single plasma samples from 32 patients on dialysis and 32 healthy individuals. We demonstrated multiple associations between recognition molecules and associated proteases of the lectin pathway and COVID-19, including COVID-19 severity. Some of these associations were unique to patients of Asian and White ethnicity. Our novel findings demonstrate that COVID19 infection alters the concentration of plasma lectin proteins and some of these changes were linked to ethnicity. This suggests a role for the lectin pathway in the host response to COVID-19 and suggest that variability within this pathway may contribute to ethnicity-associated differences in susceptibility to severe COVID-19.
Gleeson S, Noori M, Lightstone L, et al., 2021, Lesson for the clinical nephrologist: kidney transplant, COVID-19 and pregnancy, Journal of Nephrology, Vol: 34, Pages: 369-371, ISSN: 1121-8428
Botto M, Buang N, Tapeng L, et al., 2021, Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus, Nature Communications, Vol: 12, Pages: 1-15, ISSN: 2041-1723
The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.
Prendecki M, Clarke C, Brown J, et al., 2021, Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine, The Lancet, Vol: 397, Pages: 1178-1181, ISSN: 0140-6736
Gleeson S, Cardoso F, Lightstone L, et al., 2021, A new approach to de novo minimal change disease in pregnancy, Nephrology, Vol: 26, Pages: 692-693, ISSN: 1320-5358
Wiles K, Anckaert E, Holden F, et al., 2021, Anti-Mullerian hormone concentrations in women with chronic kidney disease (vol 14, pg 537, 2021), CLINICAL KIDNEY JOURNAL, Vol: 14, Pages: 1037-1038, ISSN: 2048-8505
Wiles K, Anckaert E, Holden F, et al., 2021, Anti-Mullerian hormone concentrations in women with chronic kidney disease, CLINICAL KIDNEY JOURNAL, Vol: 14, Pages: 537-542, ISSN: 2048-8505
- Author Web Link
- Cite
- Citations: 6
Willicombe M, Gleeson S, Clarke C, et al., 2021, Identification of Patient Characteristics Associated With SARS-CoV-2 Infection and Outcome in Kidney Transplant Patients Using Serological Screening, TRANSPLANTATION, Vol: 105, Pages: 151-157, ISSN: 0041-1337
- Author Web Link
- Cite
- Citations: 18
Clarke C, Lucisano G, Prendecki M, et al., 2021, Informing the risk of kidney transplantation versus remaining on the wait list in the COVID-19 era, Kidney International Reports, Vol: 6, Pages: 46-55, ISSN: 2468-0249
Introduction: There is limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of COVID-19 remains. This study aims to delineate the differential risks involved using serological methods to help define exposure rates. Methods: From a cohort of 1433 patients with ESKD, we analysed COVID-19 infection rates and outcomes in 299 wait list patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant programme closed due to COVID-19. Results: The overall mortality rate in wait list and transplant populations were equivalent, p=0.69. However, COVID-19 infection was more commonly diagnosed in the wait list patients, p=0.001, who were more likely to be tested by RT-PCR, p=0.0004. Once infection was confirmed, mortality risk was higher in the transplant patients, p=0.015. The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6% respectively, p=0.0001. After adjusting for a potential screening bias, the relative risk of death following a diagnosis of COVID-19 remained higher in transplant recipients, HR: 3.36 (1.19-9.50), p=0.022. Conclusions: In conclusion, whilst COVID-19 infection was more common in the wait list patients, a higher COVID-19 associated mortality rate was seen in transplant recipients, resulting in comparable overall mortality rates.
Waldman M, Soler MJ, Garcia-Carro C, et al., 2021, Results from the IRoc-GN international registry of patients with COVID-19 and glomerular disease suggest close monitoring, KIDNEY INTERNATIONAL, Vol: 99, Pages: 227-237, ISSN: 0085-2538
- Author Web Link
- Cite
- Citations: 27
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.