利妥昔单抗在肾移植后抗体介导的急性排斥反应中的应用五例

目的 观察肾移植受者发生抗体介导的急性排斥反应(AMR)时应用利妥昔单抗的安全性和有效性。方法 回顾分析2010年12月至2011年6月间5例发生AMR的肾移植受者的资料,患者采用利妥昔单抗(500 mg)进行治疗。记录患者的年龄、性别、发病时间、免疫诱导方案、免疫维持方案、移植肾功能、群体反应性抗体(PRA)水平、感染及其他并发症发生情况等,评价利妥昔单抗治疗的有效性和安全性。结果 5例治疗后移植肾功能均有不同程度的恢复,其中4例血肌酐恢复正常,1例血肌酐维持在300μmol/L左右。病理检查结果表明,治疗后移植肾C4d沉积明显减轻。随访6～12个月,1例发生巨细胞病毒血症,1例发生泌尿系统感染,无受者发生严重感染,人/肾存活率100％。结论 利妥昔单抗治疗肾移植术后AMR的效果和安全性均较好。     

亲属活体肾移植受者预存抗HLA抗体的处理及临床疗效观察

目的 探讨亲属活体肾移植受者预存抗HLA抗体的处理及效果.方法 移植前预存抗HLA抗体者15例,其中2例为供者特异性抗体(DSA),13例为非供者特异性抗体(NDSA).预存DSA者,术前2周开始每2～3 d行血浆置换1次,共行4～5次,每次血浆置换后静脉输注小剂量免疫球蛋白,移植当天给予利妥昔单抗375 mg/m2.术前10 d起给予他克莫司(Tac,0.1mg· kg-1·d-1)+吗替麦考酚酯(MMF,0.5 g/d).术后静脉注射免疫球蛋白(IVIG)0.2～0.4 g·kg-1·d-1,用2～3 d.预存NDSA者,术前第3天行血浆置换治疗1次,部分病例在血浆置换治疗后每天IVIG 0.6 g/kg.15例受者均采用抗胸腺细胞球蛋白(ATG)+甲泼尼龙进行诱导治疗,免疫抑制维持治疗采用Tac+ MMF+泼尼松.结果 预存DSA者,在去抗体减敏治疗后,群体反应性抗体(PRA)和淋巴细胞毒交叉配合试验(CDC)转为阴性;预存NDSA者,其CDC始终阴性,去抗体减敏治疗后仅有部分患者的PRA有所降低.2例预存DSA的受者分别于术后第14天和1个月时出现急性和交界性体液性排斥反应,抗体反弹,予以血浆置换+大剂量IVIG(1～2 g/kg)后,均能有效控制和逆转.现分别随访1年和10个月,肾功能维持良好.13例预存NDSA的受者,1例发生加速性排斥反应,予ATG治疗后逆转;1例发生急性体液性排斥反应,经大剂量IVIG治疗后逆转;1例发生急性细胞性排斥反应伴慢性化改变,甲泼尼龙冲击治疗的效果不佳,移植肾丧失功能.结论 对于预存DSA的患者,采用血浆置换+IVIG+利妥昔单抗进行去抗体减敏治疗,在其PRA和CDC转阴后再行移植,安全性和短期疗效良好.     

预存供体特异性抗体阳性肾移植6例报告并文献复习

为探讨术前预存供体特异性抗体(DSA)受者的肾移植临床效果,回顾性分析2017～2019年郑州大学第一附属医院收治的6例术前DSA阳性肾移植受者的临床资料并复习相关文献。6例受者术前群体反应性抗体(PRA)、DSA均阳性,其中3例为亲属来源受者,围手术期通过利妥昔单抗、血浆置换、丙种球蛋白及大剂量兔抗人胸腺细胞免疫球蛋白、甲泼尼龙等联合用药方案降低受者体内预存DSA。术后密切关注受者尿量、血肌酐及DSA动态变化。3例亲属肾移植受者中,1例受者术后13 d出现尿量减少,血肌酐升高,怀疑亚临床排斥反应,给予甲泼尼龙冲击治疗2 d后尿量恢复,血肌酐降至正常水平;其余2例亲属肾移植受者均于术后2周尿量及血肌酐恢复正常水平,DSA降至低危水平。另3例为公民逝世后器官捐献来源肾移植(中国Ⅱ类)受者,术前常规激素+兔抗人胸腺细胞免疫球蛋白诱导治疗后行肾移植术,术后均发生抗体介导排斥反应(AMR)导致移植肾功能延迟恢复(DGF)。通过血浆置换、利妥昔单抗、人免疫球蛋白、激素冲击等联合脱敏治疗后,受者体内DSA降低、排斥反应减轻,分别于术后15 d、35 d、27 d移植肾功能恢复。随访至今,6例DSA阳性受者肾功能均恢复良好,中位血肌酐值104(80～131)μmol/L。我中心认为,预存DSA阳性肾移植受者经过有效的术前预处理及围手术期加强免疫抑制治疗,可以取得良好的移植效果;预存DSA阳性肾移植具有可行性及安全性。     

肾移植术后早期抗体介导的急性排斥反应三例

目的 探讨肾移植术后早期抗体介导的排斥反应(AMR)诊断和治疗.方法 2011年1月至2012年8月间确诊的肾移植术后早期急性AMR病例3例.移植前受者均有HLA致敏史,其中2例群体反应性抗体(PRA)曾为阳性,但移植前已转为阴性,另1例移植前PRA-Ⅱ类抗体为强阳性.3例术前补体依赖的细胞毒性实验均为阴性.移植后1周内均出现了抗HLA抗体水平的迅速升高伴急性移植肾功能衰竭.急性AMR确诊后采用反复多次血浆置换及静脉注射丙种球蛋白(或联用硼替佐米)治疗.结果 3例移植肾穿刺病理结果均符合急性AMR的诊断标准.1例因确诊时移植肾已破裂出血而切除移植肾；1例经4次血浆置换及丙种球蛋白治疗后抗体水平显著下降且病理损伤明显好转,于术后50 d移植肾功能完全恢复正常；1例经5次血浆置换及丙种球蛋白联合硼替佐米治疗后无明显好转,于术后24 d切除移植肾.结论 HLA预致敏患者即使PRA移植前已转阴都属于肾移植术后早期急性AMR的危险人群,当出现移植肾早期原发性无功能或移植肾功能急剧下降时,及时检测HLA抗体水平和移植肾穿刺活检对确诊急性AMR十分重要.血浆置换及丙种球蛋白(或联合硼替佐米)治疗是目前首选的方法,预后与干预早晚及病理损伤程度密切相关.     

预存DSA强阳性患者二次肾移植诊治经验

预存供体特异性抗体(DSA)阳性是肾移植的禁忌证。预存DSA增加排斥反应发生率,使致敏患者存活率降低,直接影响肾移植结果。本文总结1例预存DSA强阳性患者,在二次肾移植前采用血浆置换、利妥昔单抗输注、持续抗胸腺细胞球蛋白滴注,并大剂量静脉注射免疫球蛋白等联合用药方案,抗HLAⅡ类抗体滴度显著降低。术后动态监测该受者群体反应性抗体(PRA)和DSA水平,早期发现排斥反应,及时采用地塞米松冲击、抗胸腺细胞球蛋白、大剂量静脉注射免疫球蛋白治疗排斥反应,取得良好效果,患者DSA消失。术后随访5个月,移植肾功能良好。     

肾移植和供体特异性抗体

抗体介导的排斥反应(AMR)是慢性移植肾失功的重要原因,而供体特异性抗体(DSA)是引起同种移植排斥反应的重要因素。DSA包括移植前预存DSA和移植后新生DSA(dn DSA)。预存DSA与移植后的超急性排斥反应密切相关,它对肾移植结果的影响与DSA的类型和强度有关;而dn DSA预示着AMR的开始,在慢性排斥反应中起着重要作用,影响移植肾功能和明显降低移植物的存活率。DSA介导的免疫损伤主要与损伤血管内皮细胞相关。目前对于DSA相关AMR的预防和治疗策略主要有:(1)通过血浆置换清除抗体;(2)通过联合应用CD20抗体(利妥昔单抗)+他克莫司+吗替麦考酚酯,或单用蛋白酶体抑制剂硼替佐米来抑制B细胞,减少抗体的产生;(3)利用补体C5单克隆抗体依库珠单抗阻断补体活化;(4)静脉注射免疫球蛋白;(5)脾脏切除。通过DSA监测来预防AMR具有重要临床意义。     

利妥昔单抗用于致敏患者肾移植的诱导治疗一例

体内群体反应性抗体(PRA)为阳性的患者处于致敏状态.这些抗体产生的原因尚未完全明确,输血、妊娠和再次移植等都是危险因素.为了预防移植后的排斥反应,针对致敏患者在移植前会采取一些措施,例如进行供、受者HLA配型以筛选供者;采用血浆置换和免疫吸附等方法降低患者体内预存抗体的滴度;大剂量静脉注射免疫球蛋白(IVIG)以及使用抗CD20单克隆抗体(如利妥昔单抗)等.我们对1例PRA阳性的肾移植受者使用利妥昔单抗进行诱导,效果良好,现报告如下.     

肾移植术后急性体液性排斥反应的监测及其临床意义

目的 探讨肾移植后发生急性体液性排斥反应(AHR)的可能机制,及其在临床早期诊断和防治AHR中的重要意义.方法 回顾分析2006年1月至2010年12月间296例肾移植受者的临床资料.肾移植术后,采用酶联免疫吸附试验(ELISA)动态监测受者群体反应性抗体(PRA)和供者特异性抗体(DSA)水平,采用免疫组织化学法和HE染色检查移植肾组织的病理形态学改变及C4d的沉积、浸润淋巴细胞表面分子标记.AHR诊断标准参照Banff 2005标准,并结合受者的临床相关指标.结果 296例受者中,术后共有25例发生了AHR,发生率为8.4％ (25/296).术前PRA阳性者和阴性者术后AHR的发生率分别为23.1％(6/26)和7.0％(19/270),两者比较,差异有统计学意义(P＜0.01).术后发生AHR和未发生AHR受者的DSA阳性率分别为88.0％(22/25)和0.4％(1/271),出现C4d沉积阳性率分别为80.0％(20/25)和6.7％ (4/60),两者间DSA阳性率和C4d沉积阳性率的比较,差异均有统计学意义(P＜0.01).通过调整免疫抑制方案和(或)应用静脉注射免疫球蛋白、血浆置换、抗胸腺细胞球蛋白及利妥昔单抗等治疗后,19例AHR被逆转,其余6例因治疗无效,发生移植肾破裂,导致移植肾被切除.结论 PRA和DSA在肾移植术后AHR的发生中起重要作用,术后应立即开始监测PRA和DSA,以达到预防、早期诊断和合理治疗AHR的目的,进而改善移植肾的存活.     

高致敏受者再次肾移植3例报告并文献复习

目的探讨对高致敏受者再次进行肾移植的方法。方法 3例高致敏受者再次肾移植术前选择合适的供者,包括亲属活体供肾,供受者间HLA配型良好,淋巴细胞毒交叉配型试验结果均为1%,供者特异性抗体检测阴性。免疫抑制方案采用他克莫司＋吗替麦考酚酯＋泼尼松三联方案并分别联合利妥昔单抗、抗胸腺细胞球蛋白、巴利昔单抗治疗。脱敏方案采用血浆置换或免疫吸附或血浆置换＋低剂量静脉用免疫球蛋白。结果 3例手术均成功,受者无排斥反应发生,术后1～3 d血清肌酐降至正常。3例受者随访29～42个月人肾均存活,术后未发生病毒感染及肺炎,无肝功能损害发生。结论良好的HLA配型和避免供者特异性抗体是高致敏患者再次肾移植成功的关键。采用巴利昔单抗、抗胸腺细胞球蛋白、利妥昔单抗及脱敏治疗可以减少排斥反应的发生。     

肾移植术后体液性排斥反应的研究进展

肾移植术后体液性排斥反应,即抗体介导的排斥反应(AMR)是一种预后较差的并发症。AMR由针对供者抗原的特异性抗体介导,造成血管内皮细胞损伤。随着对抗移植物抗体产生以及补体系统激活在排斥反应中作用的深入研究,AMR的治疗也出现新的策略。除了标准的AMR治疗包括血浆置换、静脉输注免疫球蛋白,新型的针对B细胞、浆细胞和补体系统的单克隆抗体,分别如:利妥昔单抗、硼替佐米、依库珠单抗等,被证明能有效治疗肾移植术后AMR。如何采用这些新型免疫抑制剂更好地控制体液免疫并延长移植物的生存,将是未来一段时间的研究热点。     

Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation

Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up.     

Clinical course and pathologic findings of successful second ABO-incompatible renal transplantation in a patient with donor-specific anti-HLA antibody

Abstract:  Donor-specific anti-HLA antibody and anti-blood group antibody could cause antibody-mediated rejection (AMR). Here, we report a successful second ABO-incompatible (ABO-I) renal transplantation in a patient with donor-specific anti-HLA antibody and its pathologic findings. A 50-yr-old woman underwent second ABO-I (A1 to O) renal transplantation. She had received the first renal graft from her mother following splenectomy in July 2003; however, graft function was lost 50 d after transplantation because of AMR. The patient received the second renal graft in November 2005, from her husband whose blood type was also A1. The recipient had donor-specific anti-HLA antibody because flow panel reactive antibody and flow cytometry crossmatch were strongly positive prior to the plasmapheresis (PP) therapy. Pre-transplant intensive immunosuppression, PP, and low dose (100 mg/m²) anti-CD20 antibody (rituximab) administration were performed as desensitization therapy. The recipient clinically developed acute rejection, and allograft biopsy specimen at day 6 post-transplant revealed AMR type II according to the Banff 2003 classification. However, the graft function was rescued by PP/low dose (100 mg/kg) intravenous immunoglobulin (IVIG) therapy, and the biopsy specimen at day 43 post-transplant showed border-line change without AMR. Rituximab and PP/low-dose IVIG therapy might improve the clinical course and pathologic findings in this AMR-related high-risk transplantation.     

肾移植术后急性体液性排斥反应的治疗

目的 总结肾移植术后急性体液性排斥反应中针对HLA抗体的检测和处理经验.方法 肾移植受者15例,术前行HLA分型、交叉配型和群体反应性抗体(PRA)的检测,术后采用他克莫司(或环孢素A)、霉酚酸酯和糖皮质激素预防排斥反应.15例于肾移植后1～14 d发生抗体介导的急性排斥反应(AMR),采用抗胸腺细胞球蛋白(100 mg/d,使用5 d)治疗,或将环孢素A转换为他克莫司,当PRA明显升高,且血清中出现供者特异性HLA抗体时,即行血浆置换(PP),共行1～5次,每次PP后静脉输注免疫球蛋白(IVIG)100～150 mg/kg,最后1次PP后给予WIG 200～500mg/kg.结果 术后出现抗供者特异性HLA Ⅰ类抗体者9例,抗HLAⅡ类抗体者4例,同时出现抗Ⅰ、Ⅱ类抗体者2例.14例的AMR逆转,1例术后发生移植肾功能恢复延迟,彩色多普勒超声波显示移植肾血流灌注差,于术后第10天切除移植肾.并行二行肾移植.2例AMR后并发急性肾小管坏死,透析后移植肾功能恢复正常.抗排斥反应治疗期间患者均未发生严重感染.随访12～52个月,1例因慢性移植肾肾病恢复血液透析治疗,1例死于心血管疾病,其余患者移植肾功能稳定.结论 将ATG、PP和IVIG联合应用能有效逆转AMR.     

Significance of low-level DSA detected by solid-phase assay in association with acute and chronic antibody-mediated rejection

We sought to clarify the controversial issue of whether detecting low‐level anti‐donor‐specific HLA antibody (HLA‐DSA) by single‐antigen flow‐bead assay (SAFB) may have a potential role in reducing acute and chronic antibody‐mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO‐compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA‐DSA was detected only by SAFB in 24 patients, although all of them showed negative T‐cell and B‐cell complement‐dependent cytotoxicity (CDC) crossmatches. The HLA‐DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA‐DSA was considered to be a desensitization candidate. The 52 patients found to have HLA‐DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double‐filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5‐year graft survival rate also improved after implementing SAFB (83.3–98.1%, P = 0.032). The RIT/DFPP‐induction protocol may improve graft survival even in patients with low‐level DSA.     

Subclinical peritubular capillaritis in serial graft biopsies in cadaveric kidney transplant recipient with pre-transplant anti-HLA antibodies

Abstract:  A 63-yr-old Japanese woman on 18-yr hemodialysis (HD) program underwent cadaveric kidney transplantation from non-heart beating donor. Pre-transplant lymphocytotoxicity test was negative, but flow cytometric cross-match and flow-cytometric panel reactive antibody (PRA) screening tests were positive. Flow-PRA single-antigen test revealed several anti-HLA antibodies including donor-specific antibody (DSA). She was treated with plasma exchange (PEX) and rituximab to prevent antibody-mediated rejection (AMR). Urinary output increased from post-operative day (POD) 5 and HD was discontinued from POD8. Graft biopsy performed on POD11 showed severe peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was negative, the case was diagnosed as subclinical AMR based on the presence of pre-transplant DSA and PTCitis with predominant PMNs. The patient was treated with additional PEX and rituximab, which increased urinary output and reduced serum creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was negative again. The patient was discharged from the hospital on POD40. During the seven months follow-up at the outpatient clinic, the sCr level has shown a slight increase. In this case, the patient had DSA, which can be detected only by flow-PRA. In both graft biopsies, C4d on PTC was negative despite the presence of severe PTCitis, and thus the diagnosis of AMR could not be established. However, the significance of subclinical PTCitis is reported perhaps as an early marker for chronic AMR and to emphasize the importance of close follow-up.     

Revisiting Traditional Risk Factors for Rejection and Graft Loss After Kidney Transplantation

Single‐antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor‐specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single‐antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third‐party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death‐censored graft survival (DCGS) and risk factors for rejection. Antibody‐mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell‐mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.     

A case of accelerated acute rejection after ABO-compatible living unrelated kidney transplantation

Abstract:  A 59-yr-old Japanese woman with chronic renal failure caused by IgA nephropathy and antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis underwent kidney transplantation from a living unrelated spousal donor. The blood type was compatible, while the human leukocyte antigen (HLA) typing showed a 5/6 locus mismatch. She had become pregnant twice by her donor and had never received blood transfusions. Complement-dependent cytotoxicity cross-match, flow cytometry cross-match (FCXM), and flow panel reactive antibody (PRA) were negative. She initially underwent one week of immunosuppression with mycophenolate mofetil (MMF) and double filtration plasmapheresis (DFPP) immediately before transplantation to reduce the risk of antibody-mediated rejection. Induction therapy consisted of MMF, tacrolimus (TAC), methylprednisolone (MP), and basiliximab. The allograft function was excellent immediately after the operation. However, the urine output and platelet count declined rapidly on post-operative day (POD) 3, while the serum creatinine (sCr) and lactate dehydrogenase levels rose gradually. Subsequently, we could not detect the diastolic arterial flow on Doppler sonography. We diagnosed accelerated acute rejection and treated her with plasma exchange (PEX), intravenous MP pulse therapy, and rituximab. The first episode biopsy on POD 7 revealed acute vascular rejection and acute antibody-mediated rejection (Banff score AMR II). Her urinary excretion increased beginning on POD 13, while the sCr level decreased gradually and reached 0.9 mg/dL on POD 22. In our retrospective analysis, the LAB screen detected donor-specific antibody (DSA). This case suggested that, for successful kidney transplantation in highly sensitized recipients, such as husband-to-wife spousal kidney transplantation with a history of pregnancy, we should keep the risk of AMR in mind, even if the sensitive antibody detection tests are negative.     

Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients

Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).     

蛋白A免疫吸附联合利妥昔单抗在PRA阳性肾移植受者中的应用七例报告

目的 探讨术前群体反应性抗体(PRA)阳性的肾移植受者应用蛋白A免疫吸附联合利妥昔单抗(RTX)治疗的效果及安全性.方法 7例中,行二次肾移植者5例,有多次妊娠史者2例.7例均行亲属活体供肾移植,供者均为男性.供、受者ABO血型相同,补体依赖细胞毒试验阴性,HLA抗原错配数2～5个.术前单纯PRAⅠ类抗体增高者2例,单纯PRAⅡ类抗体增高者2例,PRA Ⅰ、Ⅱ类抗体均增高者3例;IgG平均为13.4 g/L,IgA平均为1.78 g/L,IgM平均为1.47 g/L.术前行免疫吸附2～10次,平均为5次.当患者PRA或免疫球蛋白水平降至正常值及以下时进行移植,并于手术当天单次静脉输注RTX 600 mg,同时给予抗淋巴细胞球蛋白或抗胸腺细胞球蛋白.术后采用他克莫司(或环孢素A)、霉酚酸酯及泼尼松预防排斥反应.监测患者血肌酐及内生肌酐清除率(Ccr);临床上考虑患者发生排斥反应时,行移植肾穿刺活检;分别于术前及术后1周测定患者外周血中CD19+和CD20+细胞百分比(仅检测3例).结果 免疫吸附及RTX治疗期间,患者均未出现不良反应.行免疫吸附后,7例患者的PRA Ⅰ、Ⅱ类抗体均有所下降,IgG、IgA和IgM的平均值也有所下降.术后患者移植肾功能恢复良好,未发生移植肾功能恢复延迟,其中3例分别在术后8、10和14 d出现急性排斥反应,治疗后均逆转.术前患者外周血中CD19+细胞分别为1.98%、4.64%和4.45%,CD20+细胞分别为15.15%、2.01%和1.15%;术后1周时,其外周血中CD19+细胞分别为0.39%、0.98%和0.11%,CD20+细胞分别为0.34%、0.15%和0.01%.术后1例发生肺部巨细胞病毒感染,治疗后好转,1例因肺部烟曲霉感染而死亡,死亡时肾功能正常.结论 对于术前PRA阳性者应用蛋白A免疫吸附及RTX治疗有一定效果,经处理后患者可接受肾移植.