Management of Plasma Cell-Rich Acute Rejection in Living-Related Kidney Transplant: Role of Proteasome Inhibitor

Abbas, Khawar; Mubarak, Muhammed; Zafar, Mirza Naqi; Musharraf, Wajiha; Imam, Mehjabeen; Aziz, Tahir; Rizvi, Adibul Hassan

doi:10.6002/ect.2017.0154

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…In fact, the mean serum creatinine concentration after 12 and 24 months was just about optimal. Of note, the previously reported kidney graft outcomes after the refractory AMR treatment were noticeably worse [7,9,13,14], with several graft losses and suboptimal kidney graft excretory function. We can only hypothesize that some specific properties of bortezomib may condition its effect in the early AMR.…”

Section: Discussionmentioning

confidence: 85%

“…In some reports, such an adjuvant therapy was effective in decreasing DSAs and stabilizing kidney graft function in mid-term observation [7,9]. Nonetheless, the rate of graft loss during longer follow-up periods was high and the excretory function of still-functioning transplanted organs was markedly decreased [7,9,13,14]. As early as 2010, Walsh et al reported the first use of bortezomib along with a single dose of rituximab in two patients as a primary therapy in early post-transplant AMR, with a rapid DSAs elimination and excellent renal function at five and six months of observation [15].…”

Section: Introductionmentioning

confidence: 99%

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The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Kolonko

Słabiak-Błaż

Karkoszka

et al. 2020

JCM

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Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Kolonko

Słabiak-Błaż

Karkoszka

et al. 2020

JCM

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“…Abbas et al reported that they treated with PCAR patients with methylprednisolone (500 mg/kg), 7 sessions of plasmapheresis, antithymocyte globulin (3-5 mg/kg/day for 10 days), rituximab (2 doses at 375 mg/m 2 ), and bortezomib (1 cycle at 1.3 mg/m 2 ), with 2-year graft survival rate after rejection of 90%. [15] Other aggressive salvage therapies include intravenous immunoglobulin [4] and steroid pulse therapy. [16] However, evidence for the most effective treatment for PCAR remains limited.…”

Section: Discussionmentioning

confidence: 99%

Plasma cell-rich related acute rejection in kidney transplant: A case report and review of the literature

et al. 2022

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Rationale: Plasma cell-rich acute rejection (PCAR), a subtype of T cell-mediated rejection, is a relatively rare type of acute allograft rejection, that is usually associated with a higher rate of graft failure. However, it is difficult to diagnose PCAR precisely.Patient concerns: A 45-year-old woman who had received a kidney transplant presented with acute kidney injury and uremic symptoms approximately 1 year after transplantation.Diagnosis: A renal biopsy was performed and pathological examination revealed marked inflammation with abundant plasma cells in areas within interstitial fibrosis and tubular atrophy. The patient was diagnosed with PCAR and chronic active T cellmediated rejection (CA-TCMR) grade IA.Interventions: Immunosuppressants were administered as tacrolimus (2 mg twice daily), mycophenolate mofetil (250 mg twice daily), and prednisolone (15 mg/day) for suspected PCAR.Outcomes: The patients showed rapid deterioration in kidney function and reached impending graft failure.Lessons: PCAR is often associated with poor graft outcome. The high variability in tacrolimus levels could contribute to poor patient outcomes, leaving aggressive immunosuppressive therapy as the remaining choice for PCAR treatment.Abbreviations: AKI = acute kidney injury, CA-TCMR = chronic active T cell-mediated rejection, CD = cluster of differentiation, eGFR = estimated glomerular filtration rate, i-IFTA = inflammation of areas within interstitial fibrosis and tubular atrophy, MMF = mycophenolate mofetil, PCAR = plasma cell-rich acute rejection, PTLD = post-transplant lymphoproliferative disorder, TCMR = T cell mediated rejection.

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“…One may also consider intravenous immunoglobulin, rituximab, or bortezomib in steroid‐resistant cases because of its similar pathogenesis to AMR. Although they may be effective in renal transplant recipients, their efficacy in LTRs has not been shown 1,8 . In terms of outcomes, comparing PCAR with recurrent AIH, there are similar rates of progressive fibrosis and cirrhosis with slightly lower rates of retransplantation in PCAR (23%) 9 compared with recurrent AIH (Table 2).…”

Section: Managementmentioning

confidence: 99%

Alloimmune versus autoimmune hepatitis following liver transplantation

Harrington

Levitsky

2022

Clinical Liver Disease

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Management of Plasma Cell-Rich Acute Rejection in Living-Related Kidney Transplant: Role of Proteasome Inhibitor

Cited by 10 publications

References 24 publications

The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Plasma cell-rich related acute rejection in kidney transplant: A case report and review of the literature

Alloimmune versus autoimmune hepatitis following liver transplantation

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