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.

Wiwat Chancharoenthana,Weerapong Phumratanaprapin,Somratai Vadcharavivad,Asada Leelahavanichkul,Wassawon Ariyanon

doi:10.3390/jcm10173939

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.

Highlights

The incidence of recurrent immunoglobulin A nephropathy (IgAN) post-kidney transplantation (KT) increases in correlation with the duration of transplantation [1,2], and IgAN post-KT is categorized as a poor prognostic factor [3]
A total of 134 patients with recurrent IgAN were diagnosed by either a “for cause” or a “surveillance” biopsy, but only 64 patients with recurrent IgAN with endocapillary proliferation were included in this study
Pulse methylprednisolone 1000 mg/day for three days was commonly prescribed in patients with cellular crescent IgAN, only three patients in the rituximab with standard treatment and five patients in the conventional treatment alone received pulse methylprednisolone during the observation

Summary

Introduction

The incidence of recurrent immunoglobulin A nephropathy (IgAN) post-kidney transplantation (KT) increases in correlation with the duration of transplantation [1,2], and IgAN post-KT is categorized as a poor prognostic factor [3]. The worsening renal allograft function is associated with the characteristics of severe and active histopathology of IgAN such as endocapillary hypercellularity, crescentic formation, and thrombotic microangiopathy [4,5]. The first three histopathological lesions of renal allograft loss in KT with recurrent IgAN are segmental glomerulosclerosis (100%), endocapillary hypercellularity (91.6%), and mesangial hypercellularity (83.3%) [5]. There is no effective treatment for recurrent IgAN post-KT [6,7] because of the limited effectiveness of renin–angiotensin–aldosterone (RAS) blockade in this condition. Despite RAS blockade treatment, 30–50% of recipients with recurrent IgAN lose their renal allograft [5,10,11]. Methylprednisolone pulse therapy or increased doses of oral steroids in recurrent IgAN post-KT demonstrate the unfavorable outcomes [11] and enhanced steroid side effects, including metabolic disturbances, steroid-induced cataracts and overt immune suppression, in KT recipients

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Results

Conclusion