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Transplantation
Table 1: Renal Conditions in Which Rituximab Has Been Successfully Used
Condition Benefit References
Membranous glomerulopathy Two small cohort studies and case reports in secondary cases 28–32, 62
SLE Cohort studies; case reports 7, 13–18, 63
AAV Cohort studies, case reports 5, 19–26
Cryoglobulinaemia and MCGN Cohort studies, case reports 33–37
Relapsing MCD Case reports only 39
FSGS Case reports only 38, 40, 41, 64, 65
TMA Cohort studies and case reports 42–48
PRCA Case report 49
Transplantation rejection Cohort studies, case report 56–58, 66
PTLD Cohort studies, case reports 59–61, 67, 68
De-sensitisation:
ABO-incompatible Cohort studies, case reports 53, 54, 69–71
HLA-sensitised patients Cohort studies, case reports 50, 52
SLE = systemic lupus erythematosus; AAV = ANCA-associated vasculitis; MCGN = mesangiocapillary glomerulonephritis; MCD = minimal change disease;
FSGS = focal segmental glomerulosclerosis; TMA = thrombotic microangiopathy; PRCA = pure red cell aplasia; PTLD = post-transplantation lymphoproliferative disorder;
HLA= human leucocyte antigen.
and over 18 reports of its use in AAV, including paediatric and adult have been treated with rituximab, including focal and segmental
patients. The manufacturers estimate that approximately 10,000 patients glomerulonephritis and minimal change disease (MCD).
38,39
We have
with SLE have been treated with rituximab to date. Overall, most reports treated a number of frequently relapsing patients with MCD not
are positive, demonstrating that its use is associated with disease controlled by combinations of steroids and CNIs. Our data suggest a
remission.
13–18
In AAV, most vasculitic manifestations appear to resolve, benefit that is maintained for at least as long as the B cells are
while the more granulomatous lesions have a more variable depleted. Recurring focal segmented glomerulosclerosis (FSGS)
outcome.
5,19–26
Relapses occur when B cells are reconstituted, although following transplantation has also been successfully treated.
40,41
some cases of relapse occur without B-cell recovery. Thrombotic microangiopathies (both haemolytic–uraemic syndrome
[HUS] and thrombotic thrombocytopoenic purpura [TTP]) have been
Rituximab has been used for the treatment of idiopathic membranous successfully treated.
42–48
There has also been a single report on its use
glomerulopathy in two small cohort studies and case reports with in treating pure red cell aplasia (following erythropoietin therapy).
49
variable results
27–29
(Fervenza F, ASN, 2006). At one year it appears that
50% of patients have had a partial or complete remission of the In transplantation, rituximab has been used for desensitisation of ABO-
nephrotic syndrome. In addition, it has been successfully utilised in incompatible recipients and highly sensitised recipients.
50–55
In
addition, it has been used for the treatment of antibody-mediated
rejection
56–58
and is currently being trialled in alloantibody-associated
(C4d+) chronic rejection and following de novo alloantibody
We still remain uncertain as to how
detection. Finally, it has demonstrated efficacy in the treatment of
best to use rituximab once B cells have
post-transplant lymphoproliferative disorders (PTLD) in addition to
standard therapy.
59–61
Undoubtedly, rituximab will be used for a
returned and whether it can, or should,
number of other diverse renal conditions in the near future in an
be used as a maintenance agent.
attempt to avoid or limit more toxic therapies.
Conclusions
Rituximab, in selectively targeting the CD20-positive B cells, appears to
post-renal transplantation of membranous glomerulonephritis, be beneficial in both autoimmune and alloimmune settings, with
graft-versus-host membranous and lupus-associated (class V) relatively few adverse effects. Its use is providing an increased
membranous.
30–32
The variability in response may be related to understanding of the pathophysiology of some of the underlying
pharmacokinetic issues regarding the duration of B-cell depletion immunological conditions we are treating. We still remain uncertain as to
induced by standard-dose rituximab in proteinuric states, although how best to use it once B cells have returned and whether it can, or
more data on this topic are required. Another area of reported benefit should, be used as a maintenance agent. Over the next few years there
has been in the treatment of cryoglobulinaemia, with or without will be many reports of its novel application in diverse conditions.
mesangiocapillary glomerulonephritis both in association with or However, before its use becomes a standard therapy, randomised trials
without associated hepatitis C infection.
33–37
Other nephrotic states are required to firmly establish its true therapeutic potential. ■
1. McLaughlin P, Grillo-Lopez AJ, Link BK, et al., Rituximab FcgammaRIIIa genotype to degree of B-cell depletion by 4. Edwards JC, Szczepanski L, Szechinski J, et al., Efficacy of B-
chimeric antiCD20 monoclonal antibody therapy for relapsed rituximab in the treatment of systemic lupus erythematosus, cell-targeted therapy with rituximab in patients with rheumatoid
indolent lymphoma: half of patients respond to a four-dose Arthritis Rheum, 2003;48:455–9. arthritis, N Engl J Med, 2004;350:2572–81.
treatment program, J Clin Oncol, 1998;16:2825–33. 3. Salama A, Pusey CD, Drug insight: rituximab in renal disease 5. Keogh KA, Ytterber SR, Fervenza FC, et al., Rituximab for
2. Anolik JH, Campbell D, Felgar RE, et al., The relationship of and transplantation, Nat Clin Pract Nephrol, 2006;2:221–30. refractory Wegener’s granulomatosis: report of a prospective,
64 EUROPEAN RENAL DISEASE 2007
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