Desensitization treatment with bortezomib in a highly-sensitized patient before secondary renal transplantation:report of one case and literature review
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摘要:
目的 总结硼替佐米术前脱敏治疗用于1例高致敏二次肾移植患者的临床经验。 方法 1例移植前供体特异性抗体（DSA）阳性的二次肾移植患者，术前应用硼替佐米（1.3 mg/m2，分别于移植术前13、10、6 d，皮下注射）加低剂量免疫球蛋白。术后采用他克莫司（FK506）+麦考酚钠+甲泼尼龙三联免疫抑制方案，观察患者血清肌酐（Scr）和血尿素氮（BUN）水平、FK506血药浓度、DSA滴度、C3d结合性DSA（C3d-DSA）滴度及移植肾病理活组织检查（活检）等变化，以及不良反应。 结果 硼替佐米应用后随访12个月，Scr下降并稳定在130 μmol/L，BUN维持在3.9 mmol/L，DSA水平明显下降，C3d-DSA阴性。术后4个月和9个月移植肾病理穿刺检测均为C4d阳性，提示慢性活动性抗体介导的排斥反应（AMR）。患者出现3级周围神经病变。 结论 术前使用硼替佐米脱敏方案可有效降低肾移植受者体内DSA水平，避免高致敏二次肾移植患者发生急性排斥反应。高致敏移植患者术前脱敏治疗可选择硼替佐米在内的综合治疗。 -
关键词:
- 肾移植 /
- 供体特异性抗体(DSA) /
- 硼替佐米 /
- 脱敏 /
- 免疫球蛋白 /
- 抗体介导的排斥反应(AMR), 慢性, 活动性 /
- C4d /
- C3d /
- 周围神经病变 /
- 肾功能 /
- 他克莫司(FK506)
Abstract:Objective To summarize the clinical experience of the application of bortezomib desensitization regime prior to secondary renal transplantation in a highly-sensitized recipient. Methods At 13, 10 and 6 d prior to secondary renal transplantation, one patient positive for donor specific antibody (DSA) was subcutaneously administered with bortezomib at a dose of 1.3 mg/m2 combined with a low dose of immunoglobulin. Postoperatively, immunosuppressive regime of tacrolimus (FK506), mycophenolat sodium and methylprednisolone was adopted. The serum creatinine (Scr), blood urea nitrogen (BUN) levels, FK506 concentration, DSA titre, C3d binding DSA (C3d-DSA) titre, pathological biopsy of the renal graft and adverse reactions were observed. Results During 12-month follow-up after administration of bortezomib, the Scr level was declined and maintained at 130 μmol/L, and the BUN level was remained at 3.9 mmol/L. The DSA level was significantly decreased and the C3d-DSA was negative. At postoperative 4 and 9 months, pathological biopsy of the renal graft revealed that the patient was positive for C4d, prompting the chronic active antibody mediated rejection (AMR). The patient presented with grade Ⅲ peripheral neuropathy. Conclusions Application of preoperative bortezomib desensitization regime can effectively down-regulate the DSA level in the recipient and avert the incidence of acute rejection in highly-sensitized patients undergoing secondary renal transplantation. Comprehensive treatment using bortezomib is recommended for preoperative desensitization in the highly-sensitized transplant recipients. -
图 2 本例患者术后肾功能和FK506血药浓度的变化
Figure 2. Changes of renal function and concentration of plasma FK506 of the patient after operation
图 3 本例患者应用硼替佐米后DSA的变化
Figure 3. Changes of DSA after administration of bortezomib of the patient
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[1] Abu Jawdeh BG, Cuffy MC, Alloway RR, et al. Desensitization in kidney transplantation:review and future perspectives[J]. Clin Transplant, 2014, 28(4):494-507. DOI: 10.1111/ctr.12335. [2] Vo AA, Peng A, Toyoda M, et al. Use of intravenous immune globulin and rituximab for desensitization of highly HLA-sensitized patients awaiting kidney transplantation[J]. Transplantation, 2010, 89(9):1095-1102. DOI: 10.1097/TP.0b013e3181d21e7f. [3] Vo AA, Lukovsky M, Toyoda M, et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation[J]. N Engl J Med, 2008, 359(3):242-251. DOI: 10.1056/NEJMoa0707894. [4] Jordan SC, Choi J, Vo A. Kidney transplantation in highly sensitized patients[J]. Br Med Bull, 2015, 114(1):113-125. DOI: 10.1093/bmb/ldv013. [5] Shapiro R. Reducing antibody levels in patients undergoing transplantation[J]. N Engl J Med, 2008, 359(3):305-306. DOI: 10.1056/NEJMe0804275. [6] Perry DK, Burns JM, Pollinger HS, et al. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production[J]. Am J Transplant, 2009, 9(1):201-209. DOI: 10.1111/j.1600-6143.2008.02461.x. [7] Aubert O, Suberbielle C, Gauthe R, et al. Effect of a proteasome inhibitor plus steroids on HLA antibodies in sensitized patients awaiting a renal transplant[J]. Transplantation, 2014, 97(9):946-952. DOI:10.1097/01. TP.0000438207.42465.40. [8] Ejaz NS, Alloway RR, Halleck F, et al. Review of bortezomib treatment of antibody-mediated rejection in renal transplantation[J]. Antioxid Redox Signal, 2014, 21(17):2401-2418. DOI: 10.1089/ars.2014.5892. [9] Philogene MC, Sikorski P, Montgomery RA, et al. Differential effect of bortezomib on HLA class I and class Ⅱ antibody[J]. Transplantation, 2014, 98(6):660-665. DOI: 10.1097/TP.0000000000000132. [10] Luo H, Wu Y, Qi S, et al. A proteasome inhibitor effectively prevents mouse heart allograft rejection[J]. Transplantation, 2001, 72(2):196-202. doi: 10.1097/00007890-200107270-00005 [11] Palombella VJ, Conner EM, Fuseler JW, et al. Role of the proteasome and NF-kappaB in streptococcal cell wallinduced polyarthritis[J]. Proc Natl Acad Sci U S A, 1998, 95(26):15671-15676. doi: 10.1073/pnas.95.26.15671 [12] Wang X, Luo H, Chen H, et al. Role of proteasomes in T cell activation and proliferation[J]. J Immunol, 1998, 160(2):788-801. [13] Adams J. The proteasome:structure, function, and role in the cell[J]. Cancer Treat Rev, 2003, 29(Suppl 1):3-9. doi: 10.1007/7651_2015_216 [14] Nencioni A, Garuti A, Schwarzenberg K, et al. Proteasome inhibitor-induced apoptosis in human monocyte-derived dendritic cells[J]. Eur J Immunol, 2006, 36(3):681-689. doi: 10.1002/(ISSN)1521-4141 [15] Jeong J C, Jambald orj E, Kwon H Y, et al. Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation[J]. Medicine (Baltimore), 2016, 95(5):e2635. DOI: 10.1097/MD.0000000000002635. [16] Inui M, Miyazato T, Furusawa M, et al. Successful kidney transplantation after stepwise desensitization using rituximab and bortezomib in a highly HLA-sensitized and ABO incompatible high titer patient[J]. Transplant Direct, 2016, 2(8):e92. doi: 10.1097/TXD.0000000000000603 [17] Everly MJ, Everly JJ, Susskind B, et al. Bortezomib provides effective therapy for antibody-and cell-mediated acute rejection[J]. Transplantation, 2008, 86(12):1754-1761. DOI: 10.1097/TP.0b013e318190af83. [18] Sicard A, Ducreux S, Rabeyrin M, et al. Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss[J]. J Am Soc Nephrol, 2015, 26(2):457-467. DOI: 10.1681/ASN.2013101144. [19] Yang KS, Jeon H, Park Y, et al. Use of bortezomib as anti-humoral therapy in kidney transplantation[J]. J Korean Med Sci, 2014, 29(5):648-651. DOI: 10.3346/jkms.2014.29.5.648. [20] Dou QP, Goldfarb RH. Bortezomib (millennium pharmaceuticals)[J]. IDrugs, 2002, 5(8):828-834. [21] Guthoff M, Schmid-Horch B, Weisel KC, et al. Proteasome inhibition by bortezomib:effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation[J]. Transpl Immunol, 2012, 26(4):171-175. DOI: 10.1016/j.trim.2012.01.002. [22] Woodle ES, Shields AR, Ejaz NS, et al. Prospective iterative trial of proteasome inhibitor-based desensitization[J]. Am J Transplant, 2015, 15(1):101-118. DOI:10.1111/ajt. 13050. [23] Raghavan R, Jeroudi A, Achkar K, et al. Bortezomib in kidney transplant desensitization:a case report[J]. Clin Transpl, 2009:339-342. https://www.deepdyve.com/lp/wiley/bortezomib-in-abo-incompatible-kidney-transplant-desensitization-a-0Lth8zIhh7 [24] Ejaz NS, Shields AR, Alloway RR, et al. Randomized controlled pilot study of B cell-targeted induction therapy in HLA sensitized kidney transplant recipients[J]. Am J Transplant, 2013, 13(12):3142-3154. DOI: 10.1111/ajt.12493. [25] Schmidt N, Alloway RR, Walsh RC, et al. Prospective evaluation of the toxicity profile of proteasome inhibitorbased therapy in renal transplant candidates and recipients[J]. Transplantation, 2012, 94(4):352-361. doi: 10.1097/TP.0b013e318257acf6 -
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