Anti-CD20 Monoclonal Antibody (Rituximab) for the Treatment of Recurrent Idiopathic Membranous Nephropathy in a Renal Transplant Patient

Gallon, Lorenzo; Chhabra, Darshika

doi:10.1111/j.1600-6143.2006.01544.x

Cited by 38 publications

(27 citation statements)

References 17 publications

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“…From case reports demonstrating efficacy of rituximab in the treatment of both native and transplant iMN, we instituted a similar course of therapy in four transplant patients with recurrent disease (21)(22)(23). This is the first, although small, study of patients who had recurrent iMN and were treated with rituximab, and the results of therapy were encouraging.…”

Section: Discussionmentioning

confidence: 96%

Beneficial Effect of Rituximab in the Treatment of Recurrent Idiopathic Membranous Nephropathy after Kidney Transplantation

Sprangers¹,

Lefkowitz²,

Cohen³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Background and objectives: Recurrence of the original kidney disease after renal transplantation is an increasingly recognized cause of allograft loss. Idiopathic membranous nephropathy (iMN) is a common cause of proteinuria that may progress to ESRD. It is known that iMN may recur after kidney transplantation, causing proteinuria, allograft dysfunction, and allograft loss. Limited data regarding the frequency and treatment of recurrent iMN are available.Design, setting, participants, & measurements: In this single-center study, all patients who had iMN and were receiving a first kidney transplant were included. We retrospectively assessed the incidence of biopsy-confirmed recurrent iMN and compared clinical characteristics of patients with and without recurrence. In addition, the effect of treatment with rituximab on proteinuria and renal allograft function in patients with recurrent iMN was examined Results: The incidence of recurrent iMN was 44%, and recurrences occurred at a median time of 13.6 months after transplantation. Two patterns of recurrence were identified: Early and late. No predictors of recurrence or disease progression could be identified. Treatment with rituximab was effective in four of four patients in stabilizing or reducing proteinuria and stabilizing renal function.Conclusions: Recurrence of iMN is common even in the era of modern immunosuppression. Rituximab seems to be a valuable treatment option for these patients, although lager studies are needed to confirm our data.

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Section: Discussionmentioning

confidence: 96%

Beneficial Effect of Rituximab in the Treatment of Recurrent Idiopathic Membranous Nephropathy after Kidney Transplantation

Sprangers¹,

Lefkowitz²,

Cohen³

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…18 In addition, rituximab has been used to prevent the recurrence of FSGS, 19 membranous nephropathy, 20 and membranoproliferative GN. 21 Because antibodies play a key role in the pathogenesis of these diseases, rituximab was used to inhibit humoral immunity by modulating B cell function and suppressing antibody production.…”

Section: Discussionmentioning

confidence: 99%

“…21 Because antibodies play a key role in the pathogenesis of these diseases, rituximab was used to inhibit humoral immunity by modulating B cell function and suppressing antibody production. Proteinuria improved with rituximab administration, [15][16][17][18]20,21 but there was no evidence that the drug reduced antibody production. Furthermore, no change was reported in the level of donorspecific antibody and the number of CD20-positive cells in the kidney graft was not related to the improvement of proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation

Tasaki

Shimizu

Hanekamp

et al. 2014

Journal of the American Society of Nephrology

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We previously reported life-supporting a1,3-galactosyltransferase knockout (GalTKO) thymokidney xenograft survival of .2 months in baboons. However, despite otherwise normal renal function, recipients developed proteinuria with morphologic changes (podocyte effacement), a condition that presents a major obstacle to long-term studies in this model. A recent clinical study showed that rituximab therapy after allogeneic transplant prevented proteinuria possibly associated with loss of sphingomyelin phosphodiesterase acid-like 3b . Here, we demonstrate that rituximab prevents the disruption of pig podocytes in an SMPDL-3b-dependent manner in vitro and the early development of proteinuria after xenogeneic kidney transplantation in baboons. Immunofluorescence showed SMPDL-3b expression in pig glomerular epithelium; immunoprecipitation demonstrated rituximab binding to SMPDL-3b in glomeruli. Culture of isolated pig podocytes with naive baboon sera, which has preformed antipig natural antibodies, reduced SMPDL-3b expression, disrupted podocyte morphology, and decreased podocyte proliferation, whereas pretreatment with rituximab prevented these effects. Six baboons received rituximab before transplantation to deplete B cells and again in the peri-transplant period; 18 baboons treated only before transplantation served as historical controls. The onset of post-transplant proteinuria was significantly delayed in a B cell-independent manner in the animals that received peri-transplant rituximab treatment. Although further optimization of this protocol is required, these data provide intriguing clues to the mechanisms of post-transplant proteinuria in xenogeneic kidney transplantation and a potential strategy for its prevention.

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“…11 In this patient, the second biopsy was done approximately 6 months after initiation of treatment. 12 Patient identified in Figures 1 and 2.…”

Section: ) and 24 Months (N = 7) Achieved A Complete Remission (Cr; Omentioning

confidence: 99%

“…In addition, Rituximab therapy may be associated with histologic resolution of the disease (10). There are two previous single case reports of successful treatment of recurrent MN with Rituximab (11,12).…”

Section: Introductionmentioning

confidence: 99%

Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal Antibodies

El-Zoghby

Grande

Fraile

et al. 2009

American Journal of Transplantation

100

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Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2-21] months vs. 83[6-149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64-4898) at diagnosis to 4489 (898-13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.

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Anti-CD20 Monoclonal Antibody (Rituximab) for the Treatment of Recurrent Idiopathic Membranous Nephropathy in a Renal Transplant Patient

Abstract: Idiopathic membranous nephropathy (IMN) remains

Cited by 38 publications

References 17 publications

Beneficial Effect of Rituximab in the Treatment of Recurrent Idiopathic Membranous Nephropathy after Kidney Transplantation

Beneficial Effect of Rituximab in the Treatment of Recurrent Idiopathic Membranous Nephropathy after Kidney Transplantation

Rituximab Treatment Prevents the Early Development of Proteinuria following Pig-to-Baboon Xeno-Kidney Transplantation

Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal Antibodies

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