Remission of C3 glomerulopathy with rituximab as only immunosuppressive therapy

Giaime, Philippe; Daniel, Laurent; Burtey, Stéphane

doi:10.5414/cn107945

Cited by 22 publications

(16 citation statements)

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“…Genetic and serologic tests were performed on only one-third of the patients and determinations of C3NeF or other autoantibodies were not systematically collected or repeated along clinical course to evaluate the effect of immunosuppressive therapies. Other therapies that have been reported as useful in some C3GN patients, such as rituximab, 34 were not used in our patients. On the other hand, the major strengths of the study were the large number of included patients, the regular follow-up of all patients that allowed us to determine renal outcomes, the rigorous collection of clinical, biochemical, and histopathological data and the careful recording of all treatments and related side effects.…”

Section: Discussionmentioning

confidence: 87%

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis

Rabasco

Cavero

Román

et al. 2015

Kidney International

145

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C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

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Section: Discussionmentioning

confidence: 87%

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis

Rabasco

Cavero

Román

et al. 2015

Kidney International

145

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“…In addition to nonspecific nephroprotective drugs such as renin-angiotensin system blockers, several observations suggest some efficacy of immunosuppressive therapies, including eculizumab, a monoclonal anti-C5 antibody targeting the final step of complement pathway, and agents targeting T and/or B cells with a potential effect on glomerular inflammation and production of auto-antibodies activating complement AP. [24][25][26][27] In a recent study, it has been suggested that mycophenolate mofetil may improve renal survival in C3G.…”

Section: Discussionmentioning

confidence: 99%

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Chauvet

Frémeaux‐Bacchi

Petitprez

et al. 2017

Blood

Self Cite

145

115

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Key Points• Monoclonal gammopathy is associated with C3 glomerulopathy.• Specific treatment of the underlying B-cell clone improves renal survival.The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIgassociated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P 5 .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P 5 .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal

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“…However, there are few case reports published on the use of B-cell depleting therapy to decrease production of C3Nef and subsequently to reduce proteinuria and stabilize or even improve renal function (Table 2). In one report a 34-year-old patient with DDD was treated solely with rituximab [40]. Low C3 and normal C4 indicated an activation of the alternative complement pathway, and C3Nef was found to be positive.…”

Section: Rituximab In C3gn and Dddmentioning

confidence: 99%

Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

Rudnicki

2017

BioMed Research International

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Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed.

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Remission of C3 glomerulopathy with rituximab as only immunosuppressive therapy

Cited by 22 publications

References 0 publications

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis

Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies

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