Rituximab in Patients With Phospholipase A2 Receptor-Associated Membranous Nephropathy and Severe CKD

Nicolas Hanset; Emmanuel Esteve; Emmanuelle Plaisier; Catherine Johanet; Pierre-Antoine Michel; Jean-Jacques Boffa; Patrick Fievet; Laurent Mesnard; Johann Morelle; Pierre Ronco; Karine Dahan

doi:10.1016/j.ekir.2019.12.006

Rituximab in Patients With Phospholipase A2 Receptor-Associated Membranous Nephropathy and Severe CKD

Kidney Int Rep. 2019 Dec 20;5(3):331-338. doi: 10.1016/j.ekir.2019.12.006. eCollection 2020 Mar.

Authors

Nicolas Hanset^{1

2

3}, Emmanuel Esteve^{1

4

5}, Emmanuelle Plaisier^{3

4

5

6}, Catherine Johanet⁷, Pierre-Antoine Michel¹, Jean-Jacques Boffa¹, Patrick Fievet⁸, Laurent Mesnard^{4

5

9}, Johann Morelle², Pierre Ronco^{3

4

5

6}, Karine Dahan^{3

6}

Affiliations

¹ Department of Nephrology and Dialysis, Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris, France.
² Division of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
³ Nephrology Day Hospital, Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris, France.
⁴ Sorbonne Université, Université Pierre-et-Marie-Curie Paris 06, Paris, France.
⁵ Unité Mixte de Recherche_S 1155, Institut National de la Santé Et de la Recherche Médicale, Paris, France.
⁶ Centre de Référence Maladies Rares "Syndrome Néphrotique Idiopathique de l'Enfant et de l'Adulte," Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris, France.
⁷ Department of Immunology, Assistance Publique - Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France.
⁸ Department of Nephrology, Centre Hospitalier Laennec de Creil, Creil, France.
⁹ Department of Intensive Care Nephrology and Kidney Transplantation, Assistance Publique - Hôpitaux de Paris, Hôpital Tenon, Paris, France.

Abstract

Introduction: Patients with phospholipase A2 receptor (PLA2R)-associated membranous nephropathy and stage 4 or 5 chronic kidney disease are at high risk of end-stage kidney disease. In recent years, rituximab (RTX) emerged as a safe and efficient treatment for patients with PLA2R-associated membranous nephropathy. Whether its use is also appropriate in patients with an estimated glomerular filtration rate <30 ml/min per 1.73 m² has not been investigated.

Methods: We retrospectively reviewed characteristics and outcome of 13 patients with PLA2R-associated membranous nephropathy and stage 4 or 5 chronic kidney disease who received a total of 14 consecutive RTX treatments from January 2012 to March 2018. The treatment regimen consisted of either 2 weekly infusions of 375 mg/m² or 2 RTX infusions of 1 g/d two weeks apart. When needed, the regimen was repeated to achieve immunological remission.

Results: The mean estimated glomerular filtration rate, serum albumin level, and urinary protein level at the first RTX infusion were 18 ± 7 ml/min per 1.73 m², 25.2 ± 5.4 g/l, and 13.2 ± 7.5 g/d, respectively, with all patients being tested positive for serum PLA2R antibodies. Ten treatment courses led to an increase in estimated glomerular filtration rate and remission of nephrotic syndrome after a median follow-up of 40.8 months (interquartile range, 14.8-46.8). Conversely, 4 RTX treatments were unsuccessful, with patients requiring chronic hemodialysis within 1 year. The urinary albumin-to-protein ratio before treatment was predictive of renal response. Immunological remission occurred after 11 treatment courses and was associated with clinical response in 10 of 11 patients. Three patients experienced severe adverse events.

Conclusion: RTX seems effective and reasonably safe in PLA2R-associated membranous nephropathy with stage 4 or 5 chronic kidney disease. Immunological remission is associated with a good clinical outcome.

Keywords: CKD; ESKD; PLA2R; immunosuppressive treatment; membranous nephropathy; rituximab.