EXPLORING THE EFFICACY OF RITUXIMAB IN TREATMENT-RESISTANT PRIMARY FSGS

Introduction:

Primary focal segmental glomerulosclerosis (FSGS) that does not respond to treatment is likely to progress rapidly to end-stage renal disease. [1] There is limited data available on the use of rituximab in cases that do not respond to treatment. This study was conducted to investigate the effectiveness of rituximab in cases of treatment-resistant FSGS.

1. Michelle A. Hladunewich, Dan Cattran, Sanjeev M. Sethi, et al. Efficacy of Rituximab in Treatment-Resistant Focal Segmental Glomerulosclerosis With Elevated Soluble Urokinase-Type Plasminogen Activator Receptor and Activation of Podocyte β3 Integrin, Kidney International Reports, Volume 7, Issue 1, 2022, Pages 68-77

Methods:

A retrospective analysis was conducted on cases of treatment-resistant focal segmental glomerulosclerosis (FSGS) in individuals aged 18 years and older who received Rituximab between January 2020 and June 2023. Subjects with the collapsing variant, renal transplant, and pregnancy were excluded from the study. All cases were monitored for one year.

Treatment-resistant FSGS was defined as a proteinuria level exceeding 3.0 g, despite treatment with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, being unresponsive to prednisolone, and calcineurin inhibitors as per KDIGO guidelines. [2] Rituximab was administered at a dosage of 1000mg on days 1 and 15 with preinfusion treatment with acetaminophen, diphenhydramine, and methylprednisolone. Complete remission was defined as a proteinuria level <0.3g/day; partial remission as a reduction in proteinuria by >50% with a final urine protein level <3 g/d but more than >0.3 g/d; no response defined as worsening serum creatinine level >30% above baseline and/or <50% reduction or worsening proteinuria.

The primary outcome measured was the rate of remission at 12 months. The glomerular filtration rate (GFR) was calculated using the CKD-EPI equation. CD 19 levels were assessed one month after the final dose of Rituximab.

2. https://kdigo.org/wp-content/uploads/2024/05/KDIGO-2021-Glomerular-Diseases Guihapter-Updates.pdfdeline_English_2024-C

Results:

Out of 42 screened patients, 23 were included in the study. The baseline proteinuria, serum albumin and glomerular filtration rate (GFR) levels were 5.70 ± 2.11 g/d, 2.5±0.7 g/dl and 77 ± 22 ml/min, respectively.  The mean age was 33 ± 11 years. (Table 1)

A transient response at 6 months was noted in 4 patients whereas 2 patients had complete response. At 12 months, there were 4 patients in complete remission. (Table 2) No statistically significant improvement in proteinuria level was observed in the remaining subjects (4.87 ± 1.62 g/d). GFR level remained stable at 76 ± 17 ml/min.

There were 2 adverse events recorded, an infusion-related reaction and an episode of lower respiratory tract infection attributed to rituximab.

Conclusions:

Our research has shown that Rituximab was successful in inducing remission in around 20% of adult subjects with multidrug-resistant FSGS. It is imperative to delve deeper into alternative pathways that are specific to FSGS to formulate a more effective drug treatment plan.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.