Current outcomes of chronic active antibody mediated rejection – A large single center retrospective review using the updated BANFF 2013 criteria

Redfield, Robert; Ellis, Thomas M.; Zhong, Weixiong; Scalea, Joseph R.; Zens, Tiffany; Mandelbrot, Didier A.; Muth, Brenda; Panzer, Sarah E.; Samaniego, Millie; Kaufman, Dixon B.; Astor, Brad C.; Djamali, Arjang

doi:10.1016/j.humimm.2016.01.018

Cited by 73 publications

(73 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results presented here suggest tocilizumab can alter iDSA production, stabilize allograft function, reduce inflammatory markers of cAMR, and possibly improve patient and graft survival compared with survival rates for cAMR reported in the literature (34,35). We also noted that four allograft losses in our tocilizumab-treated patients occurred about 5 months after the termination of tocilizumab therapy.…”

Section: Discussionsupporting

confidence: 64%

“…We designed a rescue protocol to offer tocilizumab treatment to patients with cAMR with or without TG who had failed other treatment options. Once cAMR was diagnosed, 76 patients lost their allografts with a median graft survival of 1.9 years (34). Redfield et al evaluated graft survival in 123 patients with cAMR.…”

Section: Discussionmentioning

confidence: 99%

“…Recent data indicate that long-term outcomes of patients with cAMR and TG are very poor (34,35). Redfield et al evaluated graft survival in 123 patients with cAMR.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Assessment of Tocilizumab (Anti–Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients

Choi

Aubert

et al. 2017

American Journal of Transplantation

282

251

View full text Add to dashboard Cite

Extending the functional integrity of renal allografts is the primary goal of transplant medicine. The development of donor-specific antibodies (DSAs) posttransplantation leads to chronic active antibody-mediated rejection (cAMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses that occur in the United States. This reduces the quality and length of life for patients and increases cost. There are no approved treatments for cAMR. Evidence suggests the proinflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cAMR. We identified 36 renal transplant patients with cAMR plus DSAs and TG who failed standard of care treatment with IVIg plus rituximab with or without plasma exchange. Patients were offered rescue therapy with the anti-IL-6 receptor monoclonal tocilizumab with monthly infusions and monitored for DSAs and long-term outcomes. Tocilizumab-treated patients demonstrated graft survival and patient survival rates of 80% and 91% at 6 years, respectively. Significant reductions in DSAs and stabilization of renal function were seen at 2 years. No significant adverse events or severe adverse events were seen. Tocilizumab provides good long-term outcomes for patients with cAMR and TG, especially compared with historical published treatments. Inhibition of the IL-6-IL-6 receptor pathway may represent a novel approach to stabilize allograft function and extend patient lives.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of Tocilizumab (Anti–Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients

Choi

Aubert

et al. 2017

American Journal of Transplantation

282

251

View full text Add to dashboard Cite

show abstract

“…Different strategies combining steroid boluses, IVIG, RTX, and thymoglobulin have been evaluated for the treatment of chronic ABMR in non-controlled cohort studies 16,17,23. A recent systematic review has shown that in six retrospective controlled cohort studies evaluating the utility of RTX with or without IVIG, this treatment did not appear to reliably improve outcomes in chronic ABMR 24.…”

mentioning

confidence: 99%

Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial

Moreso

Crespo

Ruiz

et al. 2018

American Journal of Transplantation

135

102

View full text Add to dashboard Cite

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012-2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2 ± 14.4 vs. -6.6 ± 12.0 mL/min per 1.73 m , P-value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P-value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.

show abstract

“…1 Acute AMR is a significant cause of acute graft loss, whereas chronic AMR is a major cause of death-censored graft loss. 2,3 The mechanisms underlying AMR are not fully understood, and current therapies for AMR are suboptimal. Indeed, potential transplant opportunities are foregone due to the presence of donor-specific antibodies (DSAs) in highly sensitized patients because of the risk of AMR.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Chandran

Mulley

Kanellis

et al. 2018

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: Antibody-mediated rejection in transplant recipients with preexisting donor-specific antibodies is a challenging clinical situation. However, we lack suitable animal models to study this scenario. The aim of this study was to develop an animal model of acute antibody-mediated rejection of renal allografts in sensitized recipients. Materials and Methods: We used major histocompatibility complex class I and II incompatible rat strains (Dark Agouti RT1 av1 and Lewis RT1 l ), which develop aggressive rejection. Recipient Lewis rats were immunized with donor strain spleen cells 5 days before surgery to induce donor-specific antibodies. Rats underwent bilateral nephrectomy and orthotopic transplant of the donor kidney. To minimize T-cellmediated rejection while allowing the development of donor-specific antibodies, recipient animals were given tacrolimus starting the day before surgery. Results: Hyperacute rejection was not seen, but acute graft dysfunction was evident on day 1 with a rapid deterioration of graft function by day 3. Histologic damage featured glomerulopathy, capillaritis, capillary thrombosis, and acute tubular injury. Recipients exhibited high serum levels of donorspecific antibodies and deposition of immunoglobulin G and C4d on graft endothelium. Immunostaining showed substantial endothelial damage, fibrin deposition in glomerular and peritubular capillaries, and infiltrates of macrophages, neutrophils, and natural killer cells. T-cell activation was efficiently suppressed by tacrolimus. Conclusions:We have developed a clinically relevant model of acute antibody-mediated rejection in recipients with preexisting donor-specific antibodies, which is suitable for testing novel therapies.

show abstract

Current outcomes of chronic active antibody mediated rejection – A large single center retrospective review using the updated BANFF 2013 criteria

Cited by 73 publications

References 31 publications

Assessment of Tocilizumab (Anti–Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients

Assessment of Tocilizumab (Anti–Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients

Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial

Untitled

Contact Info

Product

Resources

About