TY - JOUR
T1 - Efficacy and Safety of ACE Inhibitor and Angiotensin Receptor Blocker Therapies in Primary Focal Segmental Glomerulosclerosis Treatment
T2 - A Systematic Review and Meta-Analysis
AU - Campbell, Kirk N.
AU - Pennese, Natali
AU - Zaffalon, Andrea
AU - Magalhaes, Barbara
AU - Faiella, Marina
AU - Caster, Dawn J.
AU - Radhakrishnan, Jai
AU - Tesar, Vladimir
AU - Trachtman, Howard
N1 - Funding Information:
Editorial support was provided by Courtney Breuel, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ) and was funded by Travere Therapeutics.
Funding Information:
Kirk N. Campbell, MD, Natali Pennese, PhD, Andrea Zaffalon, PhD, Barbara Magalhaes, PhD, Marina Faiella, PhD, Dawn J. Caster, MD, Jai Radhakrishnan, MD, Vladimir Tesar, MD, and Howard Trachtman, MD, Research idea and study design: BM, NP, AZ, MF; data extraction and analysis: BM, NP, AZ, MF; data interpretation: DJC, KNC, JR, VT, HT. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This systematic literature review was funded by Travere Therapeutics, Inc. Travere Therapeutics did not have a role in the study design; collection, analysis, and interpretation of the data; writing of the report; or the decision to submit the report for publication. Dr Campbell has received consultancy fees from Travere Therapeutics, Inc. Aurinia Pharmaceuticals, Goldfinch, and Mallinckrodt. Drs Pennese, Zaffalon, Magalhaes, and Faiella have received consultancy fees from Travere Therapeutics, Inc. Dr Caster has received consultancy fees from Aurinia Pharmaceuticals, Calliditas Therapeutics, GlaxoSmithKline, and Travere Therapeutics, Inc. Dr Radhakrishnan has no competing interests to declare. Dr Tesar has received consultancy fees from AbbVie, Amgen, Bayer, Boehringer Ingelheim, ChemoCentryx, and Fresenius Medical Care. Dr Trachtman has received consultancy fees from ChemoCentryx, Kaneka Corporation, and Otsuka Pharmaceutical; was previously a consultant to Genzyme and Optherion; and has consultancy agreements with Goldfinch Biopharma and Travere Therapeutics, Inc. through NYU. Editorial support was provided by Courtney Breuel, ELS, of MedVal Scientific Information Services, LLC (Princeton, NJ) and was funded by Travere Therapeutics. Received September 29, 2021. Evaluated by 2 external peer reviewers, with direct editorial input from an Associate Editor and the Editor-in-Chief. Accepted in revised form January 24, 2022.
Funding Information:
This systematic literature review was funded by Travere Therapeutics, Inc. Travere Therapeutics did not have a role in the study design; collection, analysis, and interpretation of the data; writing of the report; or the decision to submit the report for publication.
Publisher Copyright:
© 2022 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - Rationale and Objective: Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (renin-angiotensin-aldosterone system [RAAS] inhibitor) to control proteinuria in primary and genetic focal segmental glomerulosclerosis (FSGS) follows guidelines based on other proteinuria-related kidney diseases. There is no consensus on the efficacy and safety of RAAS inhibitor therapies in primary and genetic FSGS. This systematic review assessed the effects of RAAS inhibitor therapy on kidney outcomes in these patients. Study Design: Systematic review of randomized controlled trials, interventional nonrandomized studies, observational studies, and retrospective studies. Setting & Study Populations: Patients with primary and genetic FSGS. Selection Criteria for Studies: PubMed, Cochrane Library, and Embase. Data Extraction: 2 investigators independently screened studies and extracted data. Analytical Approach: Results were summarized as the ratio of means (ROM) between baseline and follow-up measurements or as the hazard ratio using random-effects models. Results: 30 publications were selected; 5 were controlled trials (4 randomized controlled trials). 8 assessed RAAS inhibitor monotherapy, while the rest studied RAAS inhibitors in combination with other drugs, mainly immunosuppressants. On average, a 32% proteinuria reduction (ROM, 0.68; 95% CI, 0.47-0.98) and no change in creatinine clearance (ROM, 0.95; 95% CI, 0.77-1.16) from baseline to the last reported follow-up was observed in patients treated with RAAS inhibitor monotherapy. When a RAAS inhibitor was combined with other drugs, a 72% proteinuria reduction was observed from baseline to the last reported follow-up (ROM, 0.24; 95% CI, 0.08-0.75). The published data did not allow for the assessment of the effects of RAAS inhibitor monotherapy on estimated glomerular filtration rate and end-stage kidney disease risks. Limitations: Large study heterogeneity in design, patient populations, and treatment regimens. No access to individual patient-level data. Conclusions: This review supports the tendency to observe a proteinuria reduction with RAAS inhibitors in patients with primary FSGS. RAAS inhibitor monotherapy was associated with maintained kidney function, as shown by no change in creatinine clearance. Strong evidence to quantify the effects of RAAS inhibitor monotherapy on end-stage kidney disease and glomerular filtration rate was lacking. Larger, well-designed clinical trials are needed to better understand the effects of RAAS inhibitors on primary FSGS.
AB - Rationale and Objective: Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (renin-angiotensin-aldosterone system [RAAS] inhibitor) to control proteinuria in primary and genetic focal segmental glomerulosclerosis (FSGS) follows guidelines based on other proteinuria-related kidney diseases. There is no consensus on the efficacy and safety of RAAS inhibitor therapies in primary and genetic FSGS. This systematic review assessed the effects of RAAS inhibitor therapy on kidney outcomes in these patients. Study Design: Systematic review of randomized controlled trials, interventional nonrandomized studies, observational studies, and retrospective studies. Setting & Study Populations: Patients with primary and genetic FSGS. Selection Criteria for Studies: PubMed, Cochrane Library, and Embase. Data Extraction: 2 investigators independently screened studies and extracted data. Analytical Approach: Results were summarized as the ratio of means (ROM) between baseline and follow-up measurements or as the hazard ratio using random-effects models. Results: 30 publications were selected; 5 were controlled trials (4 randomized controlled trials). 8 assessed RAAS inhibitor monotherapy, while the rest studied RAAS inhibitors in combination with other drugs, mainly immunosuppressants. On average, a 32% proteinuria reduction (ROM, 0.68; 95% CI, 0.47-0.98) and no change in creatinine clearance (ROM, 0.95; 95% CI, 0.77-1.16) from baseline to the last reported follow-up was observed in patients treated with RAAS inhibitor monotherapy. When a RAAS inhibitor was combined with other drugs, a 72% proteinuria reduction was observed from baseline to the last reported follow-up (ROM, 0.24; 95% CI, 0.08-0.75). The published data did not allow for the assessment of the effects of RAAS inhibitor monotherapy on estimated glomerular filtration rate and end-stage kidney disease risks. Limitations: Large study heterogeneity in design, patient populations, and treatment regimens. No access to individual patient-level data. Conclusions: This review supports the tendency to observe a proteinuria reduction with RAAS inhibitors in patients with primary FSGS. RAAS inhibitor monotherapy was associated with maintained kidney function, as shown by no change in creatinine clearance. Strong evidence to quantify the effects of RAAS inhibitor monotherapy on end-stage kidney disease and glomerular filtration rate was lacking. Larger, well-designed clinical trials are needed to better understand the effects of RAAS inhibitors on primary FSGS.
KW - End-stage kidney disease
KW - end-stage renal disease
KW - focal segmental glomerulosclerosis
KW - proteinuria
KW - renin-angiotensin-aldosterone system inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85129473005&partnerID=8YFLogxK
U2 - 10.1016/j.xkme.2022.100457
DO - 10.1016/j.xkme.2022.100457
M3 - Article
AN - SCOPUS:85129473005
VL - 4
JO - Kidney Medicine
JF - Kidney Medicine
SN - 2590-0595
IS - 5
M1 - 100457
ER -