197 results found
Spensley K, Gleeson S, Martin P, et al., 2022, Comparison of vaccine effectiveness against the Omicron (B.1.1.529) variant in haemodialysis patients, Kidney International Reports, ISSN: 2468-0249
Willicombe M, Scanlon M, Loud F, et al., 2022, Should we be clinically assessing antibody responses to covid vaccines in immunocompromised people? Serological testing to assess for a vaccine response would be a step towards providing more tailored care for immunocompromised people, BMJ-BRITISH MEDICAL JOURNAL, Vol: 377, ISSN: 0959-535X
Jesudason S, Hewawasam E, Moloney B, et al., 2022, Comparison of catheters or new arteriovenous fistulas for commencement of haemodialysis in pregnant women with chronic kidney disease: an international observational study, JOURNAL OF NEPHROLOGY, ISSN: 1121-8428
Turner-Stokes T, Edwards H, Lightstone L, 2022, COVID-19 in patients with glomerular disease., Curr Opin Nephrol Hypertens, Vol: 31, Pages: 191-198
PURPOSE OF REVIEW: Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease. RECENT FINDINGS: Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population. Glucocorticoid use prior to SARS-CoV-2 infection is associated with adverse outcomes from COVID-19. Rituximab significantly attenuates serological responses to both natural infection and vaccination against SARS-CoV-2, although it is not clear whether this leads to adverse outcomes. Case reports of disease flares occurring after vaccination have been reported, but causality in any of these cases has yet to be proven and the absolute risk remains very small. SUMMARY: Patients with glomerular disease represent an at-risk group for severe COVID-19 disease and vaccination is key to reducing this risk. As immunosuppressed patients demonstrate an attenuated response to vaccination, the efficacy of a third primary dose followed by a subsequent booster is being investigated.
Waldman M, Soler MJ, García-Carro C, et al., 2022, COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry., Kidney360, Vol: 3, Pages: 293-306
Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.
Gleeson S, Lightstone L, 2022, BLISS-LN trial revisited: function matters, KIDNEY INTERNATIONAL, Vol: 101, Pages: 224-226, ISSN: 0085-2538
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
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, Teng C, Gutman T, et al., 2021, A Focus Group Study of Self-Management in Patients With Glomerular Disease, KIDNEY INTERNATIONAL REPORTS, Vol: 7, Pages: 56-67, ISSN: 2468-0249
Carter SA, Lightstone L, Cattran D, et al., 2021, 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, ISSN: 1555-9041
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
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
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
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
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.
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.
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.
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
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
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, 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
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