Rituximab in Combination With Bortezomib, Plasmapheresis, and High-Dose IVIG to Treat Antibody-Mediated Renal Allograft Rejection

Waiser, Johannes; Duerr, Michael; Schönemann, Constanze; Rudolph, Birgit; Wu, Kaiyin; Halleck, Fabian; Budde, Klemens; Lachmann, Nils

doi:10.1097/txd.0000000000000604

Cited by 14 publications

(5 citation statements)

References 24 publications

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“…The doses of cyclosporine A (CyA) and tacrolimus (Tac) were adjusted according to whole blood trough levels. 15/72 (20.8%) patients in cAMR group and 16/76 (21.1%) patients in cAAMR group were treated with six sessions PPh ( 30 ) followed by intravenous immunoglobulins (IVIG) at 1.5–2.0 g/kg. 6/72 (8.3%) patients in cAMR group and 11/76 (14.5%) patients in cAAMR group received a single dose of rituximab (375 mg/m 2 body surface area) 1 week after the last IVIG infusion; 4/72 (5.6%) patients in cAMR group and 7/76 (9.2%) patients in cAAMR received bortezomib at 1.3 mg/m 2 administered intravenously twice weekly on days 1, 4, 8 and 11 after the first IVIG infusion ( 31 ).…”

Section: Methodsmentioning

confidence: 99%

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions

Schmidt

Cuesta

et al. 2022

Front. Med.

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BackgroundTransplant glomerulopathy (TG) may indicate different disease entities including chronic AMR (antibody-mediated rejection). However, AMR criteria have been frequently changed, and long-term outcomes of allografts with AMR and TG according to Banff 2017 have rarely been investigated.Methods282 kidney allograft recipients with biopsy-proven TG were retrospectively investigated and diagnosed according to Banff'17 criteria: chronic AMR (cAMR, n = 72), chronic active AMR (cAAMR, n = 76) and isolated TG (iTG, n = 134). Of which 25/72 (34.7%) patients of cAMR group and 46/76 (60.5%) of cAAMR group were treated with antihumoral therapy (AHT).ResultsUp to 5 years after indication biopsy, no statistically significant differences were detected among iTG, cAMR and cAAMR groups in annual eGFR decline (−3.0 vs. −2.0 vs. −2.8 ml/min/1.73 m2 per year), 5-year median eGFR (21.5 vs. 16.0 vs. 20.0 ml/min/1.73 m2), 5-year graft survival rates (34.1 vs. 40.6 vs. 31.8%) as well as urinary protein excretion during follow-up. In addition, cAMR and cAAMR patients treated with AHT had similar graft and patient survival rates in comparison with those free of AHT, and similar comparing with iTG group. The TG scores were not associated with 5-year postbiopsy graft failure; whereas the patients with higher scores of chronic allograft scarring (by mm-, ci- and ct-lesions) had significantly lower graft survival rates than those with mild scores. The logistic-regression analysis demonstrated that Banff mm-, ah-, t-, ci-, ct-lesions and the eGFR level at biopsy were associated with 5-year graft failure.ConclusionsThe occurrence of TG is closely associated with graft failure independent of disease categories and TG score, and the long-term clinical outcomes were not influenced by AHT. The Banff lesions indicating progressive scarring might be better suited to predict an unfavorable outcome.

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Section: Methodsmentioning

confidence: 99%

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions

Schmidt

Cuesta

et al. 2022

Front. Med.

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“…Because not all patients (45/54, 83.3%) received tacrolimus maintenance treatment, tacrolimus was included as independent variable in the analyses. Clinical outcome of the individual groups including side effect profiles has already been described . Here, we assessed all 54 patients together by using univariate and multivariate analyses, in order to investigate, which parameters predict graft survival following diagnosis.…”

Section: Methodsmentioning

confidence: 99%

Predictors of graft survival at diagnosis of antibody‐mediated renal allograft rejection: a retrospective single‐center cohort study

Waiser

Lachmann

et al. 2019

Transpl Int

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Summary Antibody‐mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy‐proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24 months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P = 0.018 and HR 1.57; P = 0.045) and eGFR slope (beta 0.46; P < 0.001 and beta −5.47; P < 0.001). Cyclophosphamide treatment (6× 15 mg/m2) plus high‐dose intravenous immunoglobulins (IVIG) (1.5 g/kg) was superior compared with single‐dose rituximab (1× 500 mg) plus low‐dose IVIG (30 g) (HR 0.10; P = 0.008 and beta 10.70; P = 0.017) and one cycle of bortezomib (4× 1.3 mg/m2) plus low‐dose IVIG (HR 0.16; P = 0.049 and beta 11.21; P = 0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome.

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“…As this drug was used in only one patient, we could not derive any conclusion based on this finding. However, in a study done by Waiser et al ,[ 18 ] addition of bortezomib to rituximab, plasmapheresis and IVIG was not found to be beneficial in improving graft function. Instead, these patients developed increased adverse events.…”

Section: Discussionmentioning

confidence: 98%

Comparative analysis of determinants and outcome of early and late acute antibody mediated rejection (ABMR)

et al. 2023

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Introduction: Antibody-mediated rejection (ABMR) is one of the major determinants of graft survival. Although diagnostic precision and treatment options have improved, response to therapy and graft survival has not improved very significantly. The phenotypes of early and late acute ABMR differ in many ways. In this study, we assessed the clinical characteristics, response to therapy, DSA positivity, and outcomes of early and late ABMR. Methods: During the study period, 69 patients with acute ABMR diagnosed on renal graft histopathology were included with a median follow-up of 10 months after rejection. Recipients were stratified into early acute ABMR (<3 months of transplant; n = 29) and late acute ABMR (>3 months of transplant; n = 40). Graft survival, patient survival, response to therapy, and doubling of serum creatinine were assessed and compared between the two groups. Results: Baseline characteristics and immunosuppression protocols were comparable between the early and late ABMR groups. Late acute ABMR had an increased risk of doubling of serum creatinine than the early ABMR group ( P = 0.002). Graft and patient survival were not statistically different between the two groups. Response to therapy was inferior in the late acute ABMR group ( P = 0.00). Pretransplant DSA was present in 27.6% in the early ABMR group. Late acute ABMR was frequently associated with nonadherence or suboptimal immunosuppression and low DSA positivity (15%). Infections such as CMV, bacterial, and fungal infections were similar in the earlier and late ABMR groups. Conclusion: Late acute ABMR group had a poor response to anti-rejection therapy and also an increased risk of doubling of serum creatinine compared to the early acute ABMR group. There was also a tendency toward increased graft loss in late acute ABMR patients. Late acute ABMR patients are more frequently associated with nonadherence/suboptimal immunosuppression. There was also a low incidence of anti-HLA DSA positivity in late ABMR.

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Rituximab in Combination With Bortezomib, Plasmapheresis, and High-Dose IVIG to Treat Antibody-Mediated Renal Allograft Rejection

Cited by 14 publications

References 24 publications

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions

Poor Outcomes in Patients With Transplant Glomerulopathy Independent of Banff Categorization or Therapeutic Interventions

Predictors of graft survival at diagnosis of antibody‐mediated renal allograft rejection: a retrospective single‐center cohort study

Comparative analysis of determinants and outcome of early and late acute antibody mediated rejection (ABMR)

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