Comparative Long-Term Renal Allograft Outcomes of Recurrent Immunoglobulin A with Severe Activity in Kidney Transplant Recipients with and without Rituximab: An Observational Cohort Study

Abstract

Recurrent IgA nephropathy (IgAN) remains an important cause of allograft loss in renal transplantation. Due to the limited efficacy of corticosteroid in the treatment of recurrent glomerulonephritis, rituximab was used in kidney transplant (KT) recipients with severe recurrent IgAN. A retrospective cohort study was conducted between January 2015 and December 2020. Accordingly, there were 64 KT recipients with biopsy-proven recurrent IgAN with similar baseline characteristics that were treated with the conventional standard therapy alone (controls, n = 43) or together with rituximab (cases, n = 21). All of the recipients had glomerular endocapillary hypercellularity and proteinuria (>1 g/d) with creatinine clearance (CrCl) > 30 mL/min/1.73 m2 and well-controlled blood pressure using renin–angiotensin–aldosterone blockers. The treatment outcomes were renal allograft survival rate, proteinuria, and post-treatment allograft pathology. During 3.8 years of follow-up, the rituximab-based regimen rapidly decreased proteinuria within 12 months after rituximab administration and maintained renal allograft function—the primary endpoint—for approximately 3 years. There were eight recipients in the case group (38%), and none in the control group reached a complete remission (proteinuria < 250 mg/d) at 12 months after treatment. Notably, renal allograft histopathology from patients with rituximab-based regimen showed the less severe endocapillary hypercellularity despite the remaining strong IgA deposition. In conclusion, adjunctive treatment with rituximab potentially demonstrated favorable outcomes for treatment of recurrent severe IgAN post-KT as demonstrated by proteinuria reduction and renal allograft function in our cohort. Further in-depth mechanistic studies with the longer follow-up periods are recommended.

Kidney transplantation in pediatric patients with rheumatologic disorders

“…Everolimus was compared with MMF for prevention of recurrence in a small cohort of adult patients [36 ▪▪ ] and was found to be an independent predictor for recurrence-free survival; however, it did not impact death-censored graft survival. In a case series, the investigational use of rituximab was found to significantly improve function as early as 18 months postinfusion in patients with endocapillary hypercellularity, with improvement in proportion of clinical and partial remission [37 ▪▪ ]. Finally, early steroid withdrawal posttransplant has been associated with increased recurrence, though these findings have not been studied prospectively [38,39,40 ▪ ].…”

“…Historically, it has been unclear whether disease recurrence leads to premature allograft failure, primarily because of the observed high rate of recurrent disease and the finding that children [2] and adults [22,32,33,34 ▪ ,35,36 ▪▪ ,37 ▪▪ ,38,39,40 ▪ ] with IgAN and IgAV have similar or better allograft survival than other causes of ESKD. Yet, recent adult studies have clarified that recurrent disease is independently associated with increased risk of allograft failure.…”

Advances in the treatment of IgA nephropathy with biological agents

“…Such drugs are mainly used for progressive IgAN, IgAN with podocytopathy, crescentic IgAN, and the recurrence of IgAN postkidney transplantation. However, RTX and OFA have a broader range of suitable patients, including those with MCD‐like IgAN with steroid dependence or relapse, progressive IgAN, crescentic IgAN, IgAN with membranous nephropathy, and IgAN recurrence after kidney transplantation 30–34 . Telitacicept, atacicept, BION‐1301, and narsoplimab are mainly indicated for progressive IgAN, with persistent urine protein >0.5 g/day and an eGFR >30 mL/min/1.73 m² based on a background of standard ACEI or ARB treatment 37–40 .…”

“…This retrospective cohort study confirmed the efficacy and safety of adjunctive treatment with RTX for recurrent severe IgAN posttransplant, with an improvement in its long‐term prognosis. 34 …”

Recurrent Immunoglobulin A Nephropathy after Kidney Transplant—An Updated Review

“…It is thus unsurprising that this has been utilized in IgAN to ameliorate disease progression. Specifically looking at a kidney transplant population, Chancharoenthana et al randomized 64 transplant recipients with biopsy proven recurrent IgAN to either conventional therapy (n = 43) or rituximab (n = 21), all treated with RAAS blockade at baseline [79]. A total of 38% of the rituximab group vs. none of those in controls achieved complete remission, with a greater proportion of those with reduced proteinuria at 12 months.…”