Rituximab in patients with PLA2R-associated membranous nephropathy and severe chronic kidney disease

Abstract Background Patients with PLA2R-associated membranous nephropathy (PLA2R-MN) and stage 4 or 5 chronic kidney disease (CKD4-5) are at high risk for end-stage kidney disease. In recent years, rituximab (RTX) emerged as a safe and efficient treatment for patients with PLA2R-MN. Whether its use is also appropriate in patients with an estimated glomerular filtration rate (eGFR) Methods We retrospectively reviewed characteristics and outcome of 13 patients with PLA2R-MN and CKD4-5 who received a total of 14 consecutive RTX treatments, from January 2012 to March 2018. Treatment regimen consisted of either two weekly infusions of 375 mg/m2 or two 1 g doses two weeks apart. When needed, the regimen was repeated to achieve immunological remission. Results Mean eGFR, serum albumin and urine protein at the first RTX infusion were 18 ± 7 mL/min/1.73m2, 25.2 ± 5.4 g/L and 13.2 ± 7.5 g/day, respectively, with all patients being tested positive for serum PLA2R antibodies. Ten treatment courses led to an increase of eGFR and remission of the nephrotic syndrome, after a median follow-up of 40.8 months (IQR 14.8-46.8). Conversely, 4 RTX treatments were unsuccessful, with patients requiring chronic hemodialysis within one year. Urine albumin/protein ratio before treatment was predictive of renal response. Immunological remission occurred after 11 treatment courses and was associated with clinical response in 10/11 patients. Three patients experienced severe adverse events. Conclusions RTX seems effective and reasonably safe in PLA2R-MN with CKD4-5. Immunological remission is associated with a good clinical outcome.