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摘要:
目的 探讨ABO血型不相容(ABOi)亲属活体肾移植的临床疗效和安全性。 方法 回顾性分析23例ABOi亲属活体肾移植受者的临床资料。术前根据受者的初始血型抗体滴度,采取不同的个体化预处理方案,包括口服免疫抑制药+利妥昔单抗,或口服免疫抑制药+血浆置换和(或)血浆双重滤过+利妥昔单抗等,监测预处理前、后,肾移植术前及术后的血型抗体滴度和围手术期移植肾功能、相关并发症。并随访移植肾功能及相关并发症。 结果 23例ABOi亲属活体肾移植受者中,除1例术中出现超急性排斥反应,其余22例血清肌酐水平恢复良好。围手术期并发症包括4例淋巴瘘、1例尿瘘、1例肾周血肿合并T细胞介导的排斥反应、6例泌尿系统感染、1例急性肾小管坏死、1例急性胰腺炎、1例血型抗体反弹、1例原发病复发,经治疗均痊愈。截止至随访日,22例受者的移植物和受者存活率均为100%,移植肾功能良好。随访期间血型抗体滴度均≤1∶8。随访期并发症包括2例严重肺部感染、1例抗体介导的排斥反应、2例原发病复发、1例淋巴囊肿、1例泌尿系统感染、1例带状疱疹、1例BK病毒尿症和2例血糖异常。 结论 根据不同血型抗体水平选择个体化预处理方案,可以安全地实施ABOi亲体肾移植。但大剂量使用利妥昔单抗,或在高致敏受者中联合使用兔抗人胸腺细胞免疫球蛋白诱导,均可能出现严重的感染并发症。 Abstract:Objective To evaluate clinical efficacy and safety of ABO-incompatible (ABOi) living-related kidney transplantation. Methods Clinical data of 23 recipients undergoing ABOi living-related kidney transplantation were retrospectively analyzed. According to the initial blood group antibody titers in the recipients before surgery, different individualized pretreatment regimens were adopted, including oral intake of immunosuppressive drugs plus rituximab, or oral intake of immunosuppressive drugs plus plasma exchange and/or double filtration plasmapheresis plus rituximab. The blood group antibody titers before and after pretreatment, before and after kidney transplantation, and perioperative renal function and related complications were monitored. Renal allograft function and related complications were observed during postoperative follow-up. Results Among 23 recipients undergoing ABOi living-related kidney transplantation, except for one case presenting with hyperacute rejection during operation, the serum creatinine levels of the remaining 22 recipients were restored normal. Perioperative complications included lymphatic fistula in 4 cases, 1 case of urinary fistula, 1 case of perirenal hematoma complicated with T cell-mediated rejection, 6 cases of urinary system infection, 1 case of acute tubular necrosis, 1 case of acute pancreatitis, 1 case of blood group antibody titer rebound, and 1 case of primary disease recurrence, and all of these complications were cured after corresponding treatment. During postoperative follow-up, the graft and recipient survival rates of 22 recipients were 100%, and renal allograft function was normal. The blood group antibody titer were all ≤1:8 during follow-up. Complications during follow-up included 2 cases of severe lung infection, 1 case of antibody-mediated rejection, 2 cases of primary disease recurrence, 1 case of lymphocyst, 1 case of urinary system infection, 1 case of herpes zoster, 1 case of BK viruria and 2 cases of abnormal blood glucose levels. Conclusions ABOi living-related kidney transplantation may be safely performed by selecting individualized pretreatment regimens according to antibody titers by different blood groups. However, high-dose rituximab or combined use of rabbit anti-human thymocyte immunoglobulin may cause severe infectious complications in highly sensitized recipients. -
表 1 23例ABOi亲属活体肾移植受者术前预处理方案及抗体滴度变化
Table 1. Preoperative treatment protocols and antibody titres changes in 23 cases of ABOi living-related kidney transplant recipients
例序 抗体
类型术前预处理方案 初始抗体
滴度手术当日
抗体滴度术后1周
抗体滴度术后2周
抗体滴度免疫抑制药
使用时间利妥昔单抗 双重滤过
(次)血浆置换
(次)IgG IgM IgG IgM IgG IgM IgG IgM 1 抗B 术前2周 术前7、3 d 各100 mg 0 0 0 1∶2 0 1∶1 0 0 0 0 2 抗A 术前2周 术前1个月 100 mg 1 1 0 1∶16 0 1∶8 0 1∶1 0 1∶1 3 抗A 术前2周 术前14 d 100 mg 0 0 0 1∶2 0 1∶2 0 1∶1 0 1∶1 4 抗A 术前2周 术前17 d 200 mg 1 1 0 1∶16 0 1∶4 0 1∶4 0 1∶1 5 抗B 术前2周 术前13、1 d 各200 mg 0 0 0 1∶4 0 1∶4 0 0 0 0 6 抗B 术前9 d 术前5 d 500 mg 1 1 0 1∶16 0 1∶1 0 0 0 1∶1 7 抗B 术前16 d 术前12、6 d 各200 mg 2 1 0 1∶8 0 1∶2 0 0 0 1∶1 8 抗A 术前16 d 术前14 d 200 mg 2 1 1∶8 1∶32 0 1∶2 0 1∶1 0 1∶2 9 抗B 术前12 d 术前11 d 100 mg 0 0 0 1∶4 0 1∶4 0 0 0 0 10 抗B 术前26 d 术前19 d 200 mg 2 3 1∶32 1∶16 0 0 1∶2 1∶1 0 1∶1 11 抗A 术前12 d 术前10 d 200 mg 1 1 1∶4 1∶8 0 1∶2 1∶2 1∶2 1∶2 1∶2 12 抗B 术前19 d 术前7 d 200 mg 2 1 1∶16 1∶8 1∶4 1∶4 0 1∶1 0 1∶1 13 抗A 术前15 d 术前14 d 200 mg 1 1 1∶4 1∶16 0 1∶4 0 1∶1 0 1∶1 14 抗A 术前23 d 术前10、1 d 分别200、100 mg 1 2 1∶32 1∶64 1∶2 1∶4 1∶4 1∶4 1∶4 1∶4 15 抗A
抗B术前37 d 术前41、1 d 分别200、100 mg 10 0 1∶32
1∶161∶64
1∶161∶8
1∶21∶8
1∶2-① - - - 16 抗B 术前18 d 术前18、4 d 分别200、100 mg 3 0 1∶2 1∶8 0 1∶2 0 1∶1 0 1∶1 17 抗B 术前22 d 术前22、1 d 分别200、100 mg 4 1 1∶4 1∶8 0 1∶1 0 1∶1 0 1∶1 18 抗B 术前12 d 术前2 d 200 mg 2 0 1∶2 1∶8 0 1∶2 0 1∶1 0 1∶1 19 抗A 术前54 d 术前54 d 200 mg 10 4 1∶4 1∶64 0 1∶4 0 1∶1 0 1∶1 20 抗A 术前48 d 术前50 d 200 mg 8 8 1∶64 1∶128 0 1∶4 1∶4 1∶4 1∶4 1∶4 21 抗B 术前20 d 术前20 d 200 mg 5 2 0 1∶128 0 1∶4 0 1∶64 0 1∶8 22 抗B 术前9 d 术前9 d 200 mg 1 0 1∶8 1∶8 1∶2 1∶2 0 0 0 0 23 抗B 术前14 d 术前14、1 d 分别200、100 mg 1 0 1∶8 1∶8 0 1∶2 0 1∶1 0 1∶1 注:①-为无数据。 -
[1] ROODNAT JI, KAL-VAN GESTEL JA, ZUIDEMA W, et al. Successful expansion of the living donor pool by alternative living donation programs[J]. Am J Transplant, 2009, 9(9): 2150-2156. DOI: 10.1111/j.1600-6143.2009.02745.x. [2] KOO TY, YANG J. Current progress in ABO-incompatible kidney transplantation[J]. Kidney Res Clin Pract, 2015, 34(3): 170-179. DOI: 10.1016/j.krcp.2015.08.005. [3] AIKAWA A, SAITO K, TAKAHASHI K. Trends in ABO-incompatible kidney transplantation[J]. Exp Clin Transplant, 2015, 13(Suppl 1): 18-22. [4] TASAKI M, YOSHIDA Y, MIYAMOTO M, et al. Identification and characterization of major proteins carrying ABO blood group antigens in the human kidney[J]. Transplantation, 2009, 87(8): 1125-1133. DOI: 10.1097/TP.0b013e31819e0054. [5] TASAKI M, TATENO H, SATO T, et al. Hyporesponsiveness against donor's ABO antigens of renal grafts after ABO-incompatible kidney transplantation[J]. Clin Exp Nephrol, 2023, 27(1): 89-95. DOI: 10.1007/s10157-022-02280-3. [6] GUY P, DELAS A, ESPOSITO L, et al. Progression of histological lesions after ABO incompatible kidney transplantation[J]. Front Immunol, 2022, 13: 969998. DOI: 10.3389/fimmu.2022.969998. [7] RIVERA CF, RODRIGUEZ MC, HERMIDA TF, et al. Isoagglutinin titers in ABO-incompatible kidney transplant[J]. Transplant Proc, 2021, 53(9): 2675-2677. DOI: 10.1016/j.transproceed.2021.07.059. [8] SCURT FG, EWERT L, MERTENS PR, et al. Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis[J]. Lancet, 2019, 393(10185): 2059-2072. DOI: 10.1016/S0140-6736(18)32091-9. [9] ZSCHIEDRICH S, JÄNIGEN B, DIMOVA D, et al. One hundred ABO-incompatible kidney transplantations between 2004 and 2014: a single-centre experience[J]. Nephrol Dial Transplant, 2016, 31(4): 663-671. DOI: 10.1093/ndt/gfv388. [10] OKUMI M, TOKI D, NOZAKI T, et al. ABO-incompatible living kidney transplants: evolution of outcomes and immunosuppressive management[J]. Am J Transplant, 2016, 16(3): 886-896. DOI: 10.1111/ajt.13502. [11] MARITATI F, BINI C, CUNA V, et al. Current perspectives in ABO-incompatible kidney transplant[J]. J Inflamm Res, 2022, 15: 3095-3103. DOI: 10.2147/JIR.S360460. [12] 岳文龙, 刘佳, 李晓虎, 等. ABO血型不相容活体肾移植23例临床分析[J]. 临床泌尿外科杂志, 2022, 37(7): 521-526. DOI: 10.13201/j.issn.1001-1420.2022.07.007.YUE WL, LIU J, LI XH, et al. ABO-incompatible living donor kidney transplantation: clinical analysis of 23 cases[J]. J Clin Urol, 2022, 37(7): 521-526. DOI: 10.13201/j.issn.1001-1420.2022.07.007. [13] HEW EY, KESSARIS N, STOJANOVIC J, et al. Successful ABO and HLA incompatible kidney transplantation in children in the UK[J]. Pediatr Nephrol, 2023, 38(2): 529-535. DOI: 10.1007/s00467-022-05583-5. [14] PANDEY P, SETYA D, SINHA VK, et al. Outcome of desensitization in human leukocyte antigen and ABO incompatible living donor kidney transplantation: single center experience of first 200 incompatible transplants[J]. J Clin Apher, 2021, 36(3): 299-312. DOI: 10.1002/jca.21860. [15] PRASAD N, CHELLAPAN A, SRIVASTAVA A, et al. ABO-incompatible repeat kidney transplantation: coping with the 'twin immunological barrier'[J]. Indian J Nephrol, 2022, 32(1): 82-86. DOI: 10.4103/ijn.IJN_64_20. [16] WATARI S, ARAKI M, WADA K, et al. ABO blood incompatibility positively affects early graft function: single-center retrospective cohort study[J]. Transplant Proc, 2021, 53(5): 1494-1500. DOI: 10.1016/j.transproceed.2021.03.043. [17] DE WEERD AE, BETJES MGH. ABO-incompatible kidney transplant outcomes: a meta-analysis[J]. Clin J Am Soc Nephrol, 2018, 13(8): 1234-1243. DOI: 10.2215/CJN.00540118. [18] SHINODA K, HYODO Y, OGUCHI H, et al. Outcome of ABO-incompatible kidney transplantation using a modified desensitization protocol without plasmapheresis[J]. Int J Urol, 2022, 29(9): 1017-1025. DOI: 10.1111/iju.14944. [19] KIM HJ, KIM JS, YANG JJ, et al. Outcome of ABO-incompatible kidney transplantation according to ABO type of transfused plasma: comparative analysis between "universal" AB and donor-type plasma[J]. Lab Med, 2022, 53(4): 369-375. DOI: 10.1093/labmed/lmab122. [20] OKADA M, NARUMI S, HASEGAWA Y, et al. Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: a single-center retrospective cohort study[J]. Clin Transplant, 2023, 37(2): e14915. DOI: 10.1111/ctr.14915. [21] SASAKI H, HOTTA K, MITSUKE A, et al. Long-term outcome of ABO-incompatible kidney transplantation in patients treated with low-dose rituximab regimen[J]. Transplant Proc, 2021, 53(3): 989-994. DOI: 10.1016/j.transproceed.2020.10.023. [22] 王毅, 罗志刚, 桂培根, 等. 供、受者ABO血型不相容保留受者脾脏的亲属活体供肾移植一例[J]. 中华器官移植杂志, 2007, 28(11): 694-695. DOI: 10.3760/cma.j.issn.0254-1785.2007.11.017.WANG Y, LUO ZG, GUI PG, et al. ABO incompatibility between donor and recipient: a case of living donor kidney transplantation which retained the recipient's spleen[J]. Chin J Organ Transplant, 2007, 28(11): 694-695. DOI: 10.3760/cma.j.issn.0254-1785.2007.11.017. [23] 蒋鸿涛, 李涛, 任坤, 等. ABO血型不相容亲属活体肾移植的多中心研究[J]. 中华器官移植杂志, 2020, 41(5): 259-264. DOI: 10.3760/cma.j.cn421203-20200416-00120.JIANG HT, LI T, REN K, et al. Preliminary results of multicenter studies on ABO-incompatible kidney transplantation[J]. Chin J Organ Transplant, 2020, 41(5): 259-264. DOI: 10.3760/cma.j.cn421203-20200416-00120. [24] LANGHORST C, GANNER A, SCHNEIDER J, et al. Long-term follow-up of ABO-incompatible kidney transplantation in freiburg, germany: a single-center outcome report[J]. Transplant Proc, 2021, 53(3): 848-855. DOI: 10.1016/j.transproceed.2020.09.001. [25] LOPAU K, SYAMKEN K, RUBENWOLF P, et al. Impact of mycophenolate mofetil on wound complications and lymphoceles after kidney transplantation[J]. Kidney Blood Press Res, 2010, 33(1): 52-59. DOI: 10.1159/000289573. [26] JHA PK, BANSAL SB, RANA A, et al. ABO-incompatible kidney transplantation in india: a single-center experience of first hundred cases[J]. Indian J Nephrol, 2022, 32(1): 42-46. DOI: 10.4103/ijn.IJN_465_20. [27] SHAH Y, ALMESHARI K, BROERING D, et al. ABO-incompatible kidney transplantation: low rates of infectious complications and excellent patient survival[J]. Transplant Proc, 2019, 51(2): 512-516. DOI: 10.1016/j.transproceed.2019.01.002. [28] GARCÍA-SOBRINO R, VAZQUEZ-MARTUL D, FERNÁNDEZ-RIVERA C, et al. Postoperative events in incompatible living donor kidney transplant recipients undergoing prior desensitization[J]. Transplant Proc, 2023, 55(7): 1575-1580. DOI: 10.1016/j.transproceed.2023.04.047. [29] MOHAMED M, SWEENEY T, ALKHADER D, et al. ABO incompatibility in renal transplantation[J]. World J Transplant, 2021, 11(9): 388-399. DOI: 10.5500/wjt.v11.i9.388. [30] MANOOK M, JOHNSON R, ROBB M, et al. Changing patterns of clinical decision making: are falling numbers of antibody incompatible transplants related to the increasing success of the UK Living Kidney Sharing Scheme? a national cohort study[J]. Transpl Int, 2021, 34(1): 153-162. DOI: 10.1111/tri.13776. [31] YIN S, TAN Q, YANG Y, et al. Transplant outcomes of 100 cases of living-donor ABO-incompatible kidney transplantation[J]. Chin Med J (Engl), 2022, 135(19): 2303-2310. DOI: 10.1097/CM9.0000000000002138. [32] BORGOGNO P, FERNÁNDEZ P, DOUTHAT W, et al. ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina[J]. Medicina (B Aires), 2021, 81(6): 986-995. [33] DE WEERD AE, VAN DEN BRAND JAJG, BOUWSMA H, et al. ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis[J]. Transpl Int, 2021, 34(12): 2706-2719. DOI: 10.1111/tri.14145. [34] HIRZEL C, PROJER L, ATKINSON A, et al. Infection risk in the first year after ABO-incompatible kidney transplantation: a nationwide prospective cohort study[J]. Transplantation, 2022, 106(9): 1875-1883. DOI: 10.1097/TP.0000000000004109. [35] BEGUM NAS, KASHEM TS, NOBI F, et al. Experiences of performing ABO-incompatible kidney transplantation in Bangladesh[J]. Korean J Transplant, 2022, 36(2): 111-118. DOI: 10.4285/kjt.22.0014.