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Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study

BACKGROUND: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportiona...

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Autores principales: Xu, Chi, Goh, Kim Ling, Abeyaratne, Asanga, Priyadarshana, Kelum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254616/
https://www.ncbi.nlm.nih.gov/pubmed/35787253
http://dx.doi.org/10.1186/s12882-022-02849-w
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author Xu, Chi
Goh, Kim Ling
Abeyaratne, Asanga
Priyadarshana, Kelum
author_facet Xu, Chi
Goh, Kim Ling
Abeyaratne, Asanga
Priyadarshana, Kelum
author_sort Xu, Chi
collection PubMed
description BACKGROUND: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646–651, 1993; Segasothy et al., Lupus 10:439–444, 2001; Bossingham, Lupus 12:327–331, 2003; Grennan et al., Aust N Z J Med 25:182–183, 1995). METHODS: We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1(st) Jan 2010 to 31(st) Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student’s t-test or Mann–Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher’s exact test. Time-to-event data was compared using the Kaplan–Meier method and Log-rank test. Count data were assessed using the Poisson’s regression method and expressed as incident rate ratio. RESULTS: Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89–15.09, p = 0.073). CONCLUSION: Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.
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spelling pubmed-92546162022-07-06 Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study Xu, Chi Goh, Kim Ling Abeyaratne, Asanga Priyadarshana, Kelum BMC Nephrol Research BACKGROUND: Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646–651, 1993; Segasothy et al., Lupus 10:439–444, 2001; Bossingham, Lupus 12:327–331, 2003; Grennan et al., Aust N Z J Med 25:182–183, 1995). METHODS: We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1(st) Jan 2010 to 31(st) Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student’s t-test or Mann–Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher’s exact test. Time-to-event data was compared using the Kaplan–Meier method and Log-rank test. Count data were assessed using the Poisson’s regression method and expressed as incident rate ratio. RESULTS: Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89–15.09, p = 0.073). CONCLUSION: Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question. BioMed Central 2022-07-04 /pmc/articles/PMC9254616/ /pubmed/35787253 http://dx.doi.org/10.1186/s12882-022-02849-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xu, Chi
Goh, Kim Ling
Abeyaratne, Asanga
Priyadarshana, Kelum
Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title_full Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title_fullStr Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title_full_unstemmed Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title_short Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia – a single centre study retrospective study
title_sort induction therapy and outcome of proliferative lupus nephritis in the top end of northern australia – a single centre study retrospective study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254616/
https://www.ncbi.nlm.nih.gov/pubmed/35787253
http://dx.doi.org/10.1186/s12882-022-02849-w
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