Background <p>Antibody-mediated rejection (AMR) continues to be a significant contributor to graft failure among transplant recipients. The standard therapeutic regimen for AMR typically encompasses glucocorticoids, intravenous immunoglobulin (IVIG), and plasmapheresis, with rituximab selectively incorporated into treatment protocols. This study aimed to retrospectively evaluate graft function, patient and graft survival rates, and biopsy findings in kidney transplant recipients diagnosed with AMR who were treated with rituximab.</p> Methods <p>We conducted a retrospective analysis of kidney transplant recipients who were diagnosed with AMR or mixed rejection at the Izmir City Hospital Organ Transplantation Center between January 2009 and December 2024. The patient cohort was stratified into two groups based on whether or not they received rituximab as part of their treatment regimen for AMR. All patients within the study received standard immunosuppressive maintenance therapy and induction therapy. The diagnosis of AMR was established according to the Banff 2017 classification criteria, and treatment outcomes were evaluated through the analysis of protocol, indication, and follow-up biopsies.</p> Results <p>A total of 56 patients were enrolled in the study, with 31 patients in the rituximab-treated group and 25 patients in the control group (non-rituximab group). Notably, the rituximab-treated group exhibited a significantly higher rate of pre-transplant Class I panel reactive antibody (PRA) positivity (<i>p</i> = 0.018) and experienced earlier episodes of rejection (<i>p</i> = 0.027). Following rejection treatment, a more pronounced improvement in renal function was observed in the rituximab-treated group, as evidenced by a greater reduction in serum creatinine levels (<i>p</i> = 0.026), while the increase in eGFR did not reach statistical significance (<i>p</i> = 0.052), although a trend toward higher values was observed At the final follow-up assessment, creatinine levels remained significantly lower in the rituximab-treated group (<i>p</i> = 0.041), and the incidence of graft loss was lower in this group. While not statistically significant, graft survival rates trended higher in the rituximab-treated group. Histological evaluation revealed improvements in inflammation scores in both groups. However, the regression of C4d positivity on biopsy was significantly more pronounced in the rituximab-treated group (<i>p</i> = 0.001), with a higher rate of conversion to C4d negativity (70% vs. 61%). BK viremia was more frequently detected in the rituximab-treated group (<i>p</i> = 0.049); however, despite the higher incidence, graft loss due to BK nephropathy remained infrequent.</p> Conclusions <p>In kidney transplant recipients experiencing AMR, treatment with rituximab was associated with enhanced graft function, reduced rates of graft loss, and favorable pathological outcomes in the short-term, among patients with early-stage AMR and high immunological risk.</p> Clinical trial number <p>Not applicable.</p>

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Rituximab in antibody-mediated rejection following kidney transplantation: clinical and pathological outcomes

  • Banu Yilmaz,
  • Adam Uslu,
  • Funda Taşli,
  • Raika Durusoy,
  • Sait Murat Doğan,
  • Gökalp Okut,
  • Mehmet Alperen Uğur,
  • Emre Kocabaş

摘要

Background

Antibody-mediated rejection (AMR) continues to be a significant contributor to graft failure among transplant recipients. The standard therapeutic regimen for AMR typically encompasses glucocorticoids, intravenous immunoglobulin (IVIG), and plasmapheresis, with rituximab selectively incorporated into treatment protocols. This study aimed to retrospectively evaluate graft function, patient and graft survival rates, and biopsy findings in kidney transplant recipients diagnosed with AMR who were treated with rituximab.

Methods

We conducted a retrospective analysis of kidney transplant recipients who were diagnosed with AMR or mixed rejection at the Izmir City Hospital Organ Transplantation Center between January 2009 and December 2024. The patient cohort was stratified into two groups based on whether or not they received rituximab as part of their treatment regimen for AMR. All patients within the study received standard immunosuppressive maintenance therapy and induction therapy. The diagnosis of AMR was established according to the Banff 2017 classification criteria, and treatment outcomes were evaluated through the analysis of protocol, indication, and follow-up biopsies.

Results

A total of 56 patients were enrolled in the study, with 31 patients in the rituximab-treated group and 25 patients in the control group (non-rituximab group). Notably, the rituximab-treated group exhibited a significantly higher rate of pre-transplant Class I panel reactive antibody (PRA) positivity (p = 0.018) and experienced earlier episodes of rejection (p = 0.027). Following rejection treatment, a more pronounced improvement in renal function was observed in the rituximab-treated group, as evidenced by a greater reduction in serum creatinine levels (p = 0.026), while the increase in eGFR did not reach statistical significance (p = 0.052), although a trend toward higher values was observed At the final follow-up assessment, creatinine levels remained significantly lower in the rituximab-treated group (p = 0.041), and the incidence of graft loss was lower in this group. While not statistically significant, graft survival rates trended higher in the rituximab-treated group. Histological evaluation revealed improvements in inflammation scores in both groups. However, the regression of C4d positivity on biopsy was significantly more pronounced in the rituximab-treated group (p = 0.001), with a higher rate of conversion to C4d negativity (70% vs. 61%). BK viremia was more frequently detected in the rituximab-treated group (p = 0.049); however, despite the higher incidence, graft loss due to BK nephropathy remained infrequent.

Conclusions

In kidney transplant recipients experiencing AMR, treatment with rituximab was associated with enhanced graft function, reduced rates of graft loss, and favorable pathological outcomes in the short-term, among patients with early-stage AMR and high immunological risk.

Clinical trial number

Not applicable.