Efficacy of Rituximab in Treatment-Resistant Focal Segmental Glomerulosclerosis With Elevated Soluble Urokinase-Type Plasminogen Activator Receptor and Activation of Podocyte β3 Integrin

Michelle A. Hladunewich, Dan Cattran, Sanjeev M. Sethi, Salim S. Hayek, Jing Li, Changli Wei, Sarah I. Mullin, Heather N. Reich, Jochen Reiser, Fernando C. Fervenza

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Severe, nonresponsive, primary focal segmental glomerular sclerosis (FSGS) can progress to end-stage kidney disease (ESKD) in <5 years. Soluble urokinase-type plasminogen activator receptor (suPAR) may contribute to podocyte effacement by activating podocyte β3 integrin. It has been reported as a potential permeability factor and biomarker for primary FSGS. Rituximab was found to have efficacy in case reports and small series. Whether rituximab is efficacious in patients with treatment-resistant FSGS in the context of high suPAR levels and evidence of podocyte B3 integrin activation remains unknown. Methods: In this nonblinded, open-label pilot study, the safety and efficacy of rituximab were evaluated in treatment-resistant adult patients with primary FSGS and a suPAR level > 3500 pg/ml with evidence of β3 integrin activation. Rituximab (1 g) was given on days 1 and 15. The primary outcome was proteinuria at 12 months. Results: Only 13 of 38 screened patients qualified for the study, of whom 9 consented to participate. The baseline proteinuria and glomerular filtration rate (GFR) levels were 7.70 ± 4.61 g/d and 67 ± 38 ml/min, respectively. A transient response at 6 months was noted in 2 patients without a parallel change in suPAR level. At 12 months, there was no statistically significant improvement in proteinuria level with all participants remaining nephrotic (7.27 ± 7.30 g/d). GFR level marginally declined to 60 ± 38 ml/min with one patient progressing to ESKD. There were 2 serious infections, an infusion-related reaction and leucopenia attributed to rituximab. Conclusion: Rituximab was ineffective when administered to adult patients with treatment-resistant primary FSGS with a high suPAR and evidence of podocyte activation.

Original languageEnglish (US)
JournalKidney International Reports
DOIs
StateAccepted/In press - 2021

Keywords

  • focal segmental glomerulosclerosis (FSGS)
  • nephrotic syndrome
  • rituximab
  • soluble urokinase-type plasminogen activator receptor (suPAR)
  • treatment resistance

ASJC Scopus subject areas

  • Nephrology

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