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

Dawn J Caster; Barbara Magalhaes; Natali Pennese; Andrea Zaffalon; Marina Faiella; Kirk N Campbell; Jai Radhakrishnan; Vladmir Tesar; Howard Trachtman

doi:10.1016/j.xkme.2022.100501

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

Kidney Med. 2022 Jun 11;4(8):100501. doi: 10.1016/j.xkme.2022.100501. eCollection 2022 Aug.

Authors

Dawn J Caster¹, Barbara Magalhaes², Natali Pennese², Andrea Zaffalon², Marina Faiella², Kirk N Campbell³, Jai Radhakrishnan⁴, Vladmir Tesar⁵, Howard Trachtman⁶

Affiliations

¹ Division of Nephrology and Hypertension, School of Medicine, University of Louisville, Louisville, Kentucky.
² LatticePOINT, Geneva, Switzerland.
³ Icahn School of Medicine at Mount Sinai, New York, NY.
⁴ Medical Center, Columbia University, New York, NY.
⁵ General University Hospital, Charles University, Prague, Czech Republic.
⁶ School of Medicine, Langone Medical Center, New York University, New York, NY.

Abstract

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 m²; 95% CI, -14.98 to 0.25 mL/min/1.73 m²). 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.

Keywords: Chronic kidney failure; end-stage kidney disease; end-stage renal disease; focal segmental glomerulosclerosis; immunosuppressive therapy; proteinuria.