Efficacy and Safety of Nine Immunosuppressive Agents for Primary Focal Segmental Glomerulosclerosis in Adults: a Pairwise and Network Meta-analysis

Overview

Journal Ren Fail

Publisher Informa Healthcare

Date 2024 Dec 11

PMID 39663153

Authors

Yan Zhu

Bo Chen

Gaosi Xu

Affiliations

Soon will be listed here.

Abstract

Background: Immunosuppressants are widely used as the preferred treatment for primary focal segmental glomerulosclerosis (pFSGS). Nevertheless, controversies persist regarding the effectiveness and side effects of different immunosuppressive medications.

Methods: From July 2023 until June 2024, we systematically searched PubMed, Cochrane Library, Web of Science, clinicalrials.gov, SinoMed, Chinese Biomedical, Chinese National Knowledge Infrastructure, Wanfang, and VIP information. Randomized controlled trials comparing different immunosuppressants were included in adult patients with pFSGS, with total remission (TR) and 24-h urine total protein (24-h UTP) as the main outcome measures.

Results: We identified 20 RCTs comparing nine different immunosuppressants for the final analysis. Most immunosuppressants showed better therapeutic effects in TR compared to non-immunosuppressive therapies (NIT), with risk ratios (RRs) of 2.22 (95% CI 1.41-3.50) for cyclosporin, 2.10 (1.57-2.80) for leflunomide-combined steroids, 2.01 (1.24-3.27) for chlorambucil-combined steroids, 1.98 (1.17-3.33) for tacrolimus-combined steroids, 1.89 (1.36-2.63) for cyclosporin-combined steroids, 1.67 (1.28-2.18) for mycophenolate mofetil-combined steroids, and 1.47 (1.21-1.80) for steroids. Only mycophenolate mofetil-combined steroids (SMD -11, 95% CI -21 to -0.64) showed significant superiority in reducing 24-h UTP when compared with NIT. The subgroup analyses of steroids-resistant nephrotic syndrome (SRNS) patients showed that CSA + STE was significantly superior than the NIT group, with RR of 10.5 (95% CI 2.28-44.35).

Conclusion: Steroids remain the recommended initial treatment for pFSGS. For those patients with SRNS, CSA + STE might be the best choice for improving the rate of TR. LEF + STE and MMF + STE also appear to offer a steroid-saving alternative to high-dose glucocorticoids for patients.

References

Sim J, Bhandari S, Batech M, Hever A, Harrison T, Shu Y . End-Stage Renal Disease and Mortality Outcomes Across Different Glomerulonephropathies in a Large Diverse US Population. Mayo Clin Proc. 2018; 93(2):167-178. DOI: 10.1016/j.mayocp.2017.10.021. View

Haas M, Meehan S, Karrison T, SPARGO B . Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis. 1997; 30(5):621-31. DOI: 10.1016/s0272-6386(97)90485-6. View

De Vriese A, Wetzels J, Glassock R, Sethi S, Fervenza F . Therapeutic trials in adult FSGS: lessons learned and the road forward. Nat Rev Nephrol. 2021; 17(9):619-630. PMC: 8136112. DOI: 10.1038/s41581-021-00427-1. View

Huang J, Lin L, Xie J, Li X, Shen P, Pan X . Glucocorticoids in the treatment of patients with primary focal segmental glomerulosclerosis and moderate proteinuria. Clin Exp Nephrol. 2018; 22(6):1315-1323. DOI: 10.1007/s10157-018-1585-z. View

Trachtman H, Vento S, Herreshoff E, Radeva M, Gassman J, Stein D . Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group. BMC Nephrol. 2015; 16:111. PMC: 4511259. DOI: 10.1186/s12882-015-0094-5. View

Hommos M, De Vriese A, Alexander M, Sethi S, Vaughan L, Zand L . The Incidence of Primary vs Secondary Focal Segmental Glomerulosclerosis: A Clinicopathologic Study. Mayo Clin Proc. 2017; 92(12):1772-1781. PMC: 5790554. DOI: 10.1016/j.mayocp.2017.09.011. View

Gipson D, Trachtman H, Kaskel F, Greene T, Radeva M, Gassman J . Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 2011; 80(8):868-78. PMC: 3306824. DOI: 10.1038/ki.2011.195. View

Nankivell B, PNg C, OConnell P, Chapman J . Calcineurin Inhibitor Nephrotoxicity Through the Lens of Longitudinal Histology: Comparison of Cyclosporine and Tacrolimus Eras. Transplantation. 2016; 100(8):1723-31. DOI: 10.1097/TP.0000000000001243. View

Swaminathan S, Leung N, Lager D, Melton 3rd L, Bergstralh E, Rohlinger A . Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol. 2007; 1(3):483-7. DOI: 10.2215/CJN.00710805. View

10.

Salanti G, Ades A, Ioannidis J . Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol. 2010; 64(2):163-71. DOI: 10.1016/j.jclinepi.2010.03.016. View

11.

Sterne J, Savovic J, Page M, Elbers R, Blencowe N, Boutron I . RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366:l4898. DOI: 10.1136/bmj.l4898. View

12.

Cattran D, Appel G, Hebert L, Hunsicker L, Pohl M, Hoy W . A randomized trial of cyclosporine in patients with steroid-resistant focal segmental glomerulosclerosis. North America Nephrotic Syndrome Study Group. Kidney Int. 1999; 56(6):2220-6. DOI: 10.1046/j.1523-1755.1999.00778.x. View

13.

Lin L, Wang W, Wu Y, Xie J, Li X, Pan X . Consolidation Treatment and Long-Term Prognosis of Rituximab in Minimal Change Disease and Focal Segmental Glomerular Sclerosis. Drug Des Devel Ther. 2021; 15:1945-1953. PMC: 8121273. DOI: 10.2147/DDDT.S302257. View

14.

Caster D, Magalhaes B, Pennese N, Zaffalon A, Faiella M, Campbell K . Efficacy and Safety of Immunosuppressive Therapy in Primary Focal Segmental Glomerulosclerosis: A Systematic Review and Meta-analysis. Kidney Med. 2022; 4(8):100501. PMC: 9399559. DOI: 10.1016/j.xkme.2022.100501. View

15.

Heering P, Braun N, Mullejans R, Ivens K, Zauner I, Funfstuck R . Cyclosporine A and chlorambucil in the treatment of idiopathic focal segmental glomerulosclerosis. Am J Kidney Dis. 2004; 43(1):10-8. DOI: 10.1053/j.ajkd.2003.09.027. View

16.

Troyanov S, Wall C, Miller J, Scholey J, Cattran D . Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. J Am Soc Nephrol. 2005; 16(4):1061-8. DOI: 10.1681/ASN.2004070593. View

17.

Munis M, Chen Q, Hill T, Zhuo M, Schachter A, Bhandari S . Incidence and Proportion of Primary Focal Segmental Glomerulosclerosis (FSGS) among a Racially and Ethnically Diverse Adult Patient Population between 2010 and 2021. Clin J Am Soc Nephrol. 2024; . PMC: 11835197. DOI: 10.2215/CJN.0000000590. View

18.

Imbasciati E, Cagnoli L, Case N, Pasquali S, Di Filippo G, Limido D . [Controlled study of treatment of steroids and chlorambucil, in alternate months, for membranous nephropathy and focal glomerulosclerosis. Preliminary evaluation of the results]. Minerva Nefrol. 1980; 27(4):571-5. View

19.

Ponticelli C, Rizzoni G, Edefonti A, Altieri P, Rivolta E, Rinaldi S . A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. Kidney Int. 1993; 43(6):1377-84. DOI: 10.1038/ki.1993.194. View

20.

Sim J, Batech M, Hever A, Harrison T, Avelar T, Kanter M . Distribution of Biopsy-Proven Presumed Primary Glomerulonephropathies in 2000-2011 Among a Racially and Ethnically Diverse US Population. Am J Kidney Dis. 2016; 68(4):533-544. DOI: 10.1053/j.ajkd.2016.03.416. View