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Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis

RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a rare condition that can lead to kidney function decline and chronic kidney failure. Immunosuppressants are used to treat primary FSGS. However, their efficacy and safety in FSGS are not clearly established. We assessed current...

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Autores principales: Caster, Dawn J., Magalhaes, Barbara, Pennese, Natali, Zaffalon, Andrea, Faiella, Marina, Campbell, Kirk N., Radhakrishnan, Jai, Tesar, Vladmir, Trachtman, Howard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399559/
https://www.ncbi.nlm.nih.gov/pubmed/36032548
http://dx.doi.org/10.1016/j.xkme.2022.100501
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author Caster, Dawn J.
Magalhaes, Barbara
Pennese, Natali
Zaffalon, Andrea
Faiella, Marina
Campbell, Kirk N.
Radhakrishnan, Jai
Tesar, Vladmir
Trachtman, Howard
author_facet Caster, Dawn J.
Magalhaes, Barbara
Pennese, Natali
Zaffalon, Andrea
Faiella, Marina
Campbell, Kirk N.
Radhakrishnan, Jai
Tesar, Vladmir
Trachtman, Howard
author_sort Caster, Dawn J.
collection PubMed
description RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a rare condition that can lead to kidney function decline and chronic kidney failure. Immunosuppressants are used to treat primary FSGS. However, their efficacy and safety in FSGS are not clearly established. We assessed current knowledge on clinical effectiveness and safety of immunosuppressants for primary FSGS. STUDY DESIGN: Systematic review of randomized controlled trials, interventional nonrandomized controlled trials, observational studies, retrospective studies, and registries. SETTING & PARTICIPANTS: Patients with primary and genetic FSGS. SELECTION CRITERIA FOR STUDIES: Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for English-language, primary-FSGS studies from inception to 2019. Clinical outcomes were changes from baseline in proteinuria, kidney function, and kidney survival. DATA EXTRACTION: 2 investigators independently screened studies and extracted data. ANALYTICAL APPROACH: Study results were summarized using random-effects models either as ratios of means between follow-up and baseline measurements or as HRs. RESULTS: We included 98 articles. Substantial heterogeneity was observed in patient baseline characteristics and study designs. Most studies assessed treatment with corticosteroids alone or combined with other drugs, mainly immunosuppressants. Patients treated with immunosuppressants showed reduced proteinuria (14 studies; ratio of means, 0.36; 95% CI, 0.20-0.47), decreased creatinine clearance (mean difference, −25.03; 95% CI, −59.33 to −9.27) and (significantly) lower estimated glomerular filtration rates (mean difference, −7.61 mL/min/1.73 m(2); 95% CI, −14.98 to 0.25 mL/min/1.73 m(2)). Immunosuppressant therapy had an uncertain effect on reducing the chronic kidney failure risk. Hypertension and infections were the most commonly reported adverse events. LIMITATIONS: Heterogeneity in study designs, patient populations, and treatment regimens; no access to individual patient–level data. CONCLUSIONS: This systematic review supports proteinuria reduction with immunosuppressant therapy in primary FSGS over varying follow-up periods. The effects of immunosuppressants on kidney survival remain uncertain. This review underscores the need for better-designed and adequately controlled studies to assess immunosuppressant therapy in patients with primary FSGS.
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spelling pubmed-93995592022-08-25 Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis Caster, Dawn J. Magalhaes, Barbara Pennese, Natali Zaffalon, Andrea Faiella, Marina Campbell, Kirk N. Radhakrishnan, Jai Tesar, Vladmir Trachtman, Howard Kidney Med Original Research RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a rare condition that can lead to kidney function decline and chronic kidney failure. Immunosuppressants are used to treat primary FSGS. However, their efficacy and safety in FSGS are not clearly established. We assessed current knowledge on clinical effectiveness and safety of immunosuppressants for primary FSGS. STUDY DESIGN: Systematic review of randomized controlled trials, interventional nonrandomized controlled trials, observational studies, retrospective studies, and registries. SETTING & PARTICIPANTS: Patients with primary and genetic FSGS. SELECTION CRITERIA FOR STUDIES: Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for English-language, primary-FSGS studies from inception to 2019. Clinical outcomes were changes from baseline in proteinuria, kidney function, and kidney survival. DATA EXTRACTION: 2 investigators independently screened studies and extracted data. ANALYTICAL APPROACH: Study results were summarized using random-effects models either as ratios of means between follow-up and baseline measurements or as HRs. RESULTS: We included 98 articles. Substantial heterogeneity was observed in patient baseline characteristics and study designs. Most studies assessed treatment with corticosteroids alone or combined with other drugs, mainly immunosuppressants. Patients treated with immunosuppressants showed reduced proteinuria (14 studies; ratio of means, 0.36; 95% CI, 0.20-0.47), decreased creatinine clearance (mean difference, −25.03; 95% CI, −59.33 to −9.27) and (significantly) lower estimated glomerular filtration rates (mean difference, −7.61 mL/min/1.73 m(2); 95% CI, −14.98 to 0.25 mL/min/1.73 m(2)). Immunosuppressant therapy had an uncertain effect on reducing the chronic kidney failure risk. Hypertension and infections were the most commonly reported adverse events. LIMITATIONS: Heterogeneity in study designs, patient populations, and treatment regimens; no access to individual patient–level data. CONCLUSIONS: This systematic review supports proteinuria reduction with immunosuppressant therapy in primary FSGS over varying follow-up periods. The effects of immunosuppressants on kidney survival remain uncertain. This review underscores the need for better-designed and adequately controlled studies to assess immunosuppressant therapy in patients with primary FSGS. Elsevier 2022-06-11 /pmc/articles/PMC9399559/ /pubmed/36032548 http://dx.doi.org/10.1016/j.xkme.2022.100501 Text en © 2022 Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Caster, Dawn J.
Magalhaes, Barbara
Pennese, Natali
Zaffalon, Andrea
Faiella, Marina
Campbell, Kirk N.
Radhakrishnan, Jai
Tesar, Vladmir
Trachtman, Howard
Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title_full Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title_fullStr Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title_full_unstemmed Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title_short Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis
title_sort efficacy and safety of immunosuppressive therapy in primary focal segmental glomerulosclerosis: a systematic review and meta-analysis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399559/
https://www.ncbi.nlm.nih.gov/pubmed/36032548
http://dx.doi.org/10.1016/j.xkme.2022.100501
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