Journal
KIDNEY INTERNATIONAL REPORTS
Volume 7, Issue 1, Pages 68-77Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ekir.2021.10.017
Keywords
focal segmental glomerulosclerosis (FSGS); nephrotic syndrome; rituximab; soluble urokinase-type plasminogen activator receptor (suPAR); treatment resistance
Categories
Funding
- pilot project within the Nephrotic Syndrome Study Network (NEPTUNE) - National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK)
- Office for Rare Diseases Research (ORDR) at the National Institutes of Health (NIH)
- NephCure Foundation
- Halpin Foundation
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In this study, the use of rituximab in adult patients with treatment-resistant primary FSGS, high suPAR levels, and evidence of podocyte activation was found to be ineffective in improving proteinuria levels and glomerular filtration rate.
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 beta 3 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 beta 3 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.
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