肾移植受者群体反应性抗体监测的临床意义

目的 分析群体反应性抗体（PRA）监测对预测肾移植受者排斥反应发生的意义及探讨对高水平PRA受者的临床处理.方法 应用酶联免疫吸附分析法（ELISA法）动态监测肾移植受者的PRA水平,以PRA≥10%为阳性,10%≤PRA＜50%为低致敏、PRA≥50%为高致敏,并对37例术前高致敏患者行血浆置换.结果 1527例肾移植受者中,PRA阳性350例（22.9% ）,其中高致敏 94例（26.8% ）;PRA阳性组排斥反应发生率（21.1% ）高于PRA阴性组（3.8% , P〈0.01）, 术后PRA转为阳性组排斥反应发生率高于PRA无变化组（P〈0.01）,行血浆置换受者与未行血浆置换受者排斥反应发生率无差异（P〉0.05）,接受过移植、多次妊娠、多次输血受者易致敏,HLA-A、B、DR配型错配抗原〉3个受者急性排斥的发生率（16.9% ）明显高于错配抗原≤3个受者（1.7% , P〈0.01）.结论 动态监测PRA水平有助于预测排斥反应的发生.     

肾移植前对致敏患者干预治疗的方案及疗效分析

目的 总结和探讨肾移植前致敏患者干预治疗的方案及疗效分析.方法 选择2008年至2011年接受肾移植的致敏受者43例,根据术前群体反应性抗体(PRA)水平分为轻度致敏组和高度致敏组,术前经血浆置换、输注静脉用免疫球蛋白(IVIG)的干预治疗,经过HLA配型,联合应用抗人胸腺细胞免疫球蛋白(ATG)诱导治疗,应用他克莫司(Tac)、吗替麦考酚酯(MMF)和泼尼松的免疫抑制方案,术后定期检测PRA水平.所有受者随访12～36个月,观察受者/移植肾存活率,急性排斥反应的发生率,移植肾功能和PRA水平的变化,以及进行移植肾穿刺活检.结果 经干预治疗后,轻度致敏组中14例PRA完全转阴,高度致敏组中5例PRA完全转阴,其余受者PRA水平均较干预治疗前明显下降(P＜0.05).术后两组受者均出现PRA水平的爬升.轻度致敏组和高度致敏组的人存活率分别为95.6％和90％,移植肾存活率分别为82.6％和70％.轻度致敏组有3例活检证实发生急性细胞性排斥反应,高度致敏组有5例活检证实发生急性排斥反应,急性细胞性排斥反应均经甲泼尼龙冲击治疗3～5 d后逆转.两组共10例受者出现血肌酐缓慢爬升,经移植肾穿刺活检发现慢性移植肾肾病的表现.结论 血浆置换和输注IVIG的干预治疗,良好的HLA配型,ATG诱导治疗,以及应用Tac+ MMF+泼尼松的免疫抑制方案是致敏受者肾移植成功的前提.     

致敏肾移植受者抗MICA抗体的表达对术后早期排斥反应和肾功能的影响

目的 探讨致敏肾移植受者抗主要组织相容性复合物Ⅰ类链相关基因A(MICA)抗体的表达对术后早期排斥反应和肾功能的影响.方法 致敏患者(群体反应性抗体＞20%)29例,肾移植前采用蛋白A免疫吸附柱进行处理,检测吸附前后患者体内的抗MICA抗体表达情况.受者术后采用他克莫司+吗替麦考酚酯+糖皮质激素预防排斥反应.分析抗MICA抗体表达水平与排斥反应和移植肾功能的相关性.结果 29例受者中,抗MICA抗体阳性者8例(27.6%,8/29),表达6种抗体者1例,表达3种抗体者1例,仅表达1种抗体者6例.抗MICA抗体阳性组急性排斥反应发生率为37.5%(3/8),抗MICA抗体阴性组为38.1%(8/21),二者间比较,差异无统计学意义(P＞0.05).群体反应性抗体(PRA)≥40%者抗MICA抗体的表达率为43.8%(7/16),明显高于PRA＜40%者的7.7%(1/13,P＜0.05).抗MICA抗体阳性受者的血肌酐水平在术后1周时为(135.4±21.4)μmol/L,明显高于抗MICA抗体阴性者的(108.6±31.6)μmol/L(P＜0.05);术后2周时,抗MICA抗体阳性者的血肌酐降至正常范围,与阴性者比较,差异无统计学意义(P＞0.05).全部患者经蛋白A免疫吸附处理后,其抗MICA抗体持续降低.结论 抗MICA抗体在致敏患者中表达率升高,对术后早期移植肾功能的恢复有影响;蛋白A免疫吸附可有效去除致敏患者体内的抗MICA抗体.     

活体肾移植前对致敏患者的处理经验及疗效分析

目的 总结活体肾移植前对致敏患者的处理经验,并对移植效果进行分析.方法 回顾性分析609例活体肾移植受者的临床资料.根据移植前群体反应性抗体(PRA)水平将受者分为高致敏组(41例,PRA≥30％),低致敏组(102例,PRA为0～30％)和非致敏组(466例,PRA为0).所有受者经HLA抗体检测和淋巴细胞毒交叉配合试验(CDC)确认没有针对供者的HLA抗体后进行肾移植.高致敏组给予抗胸腺细胞球蛋白诱导治疗,低致敏组给予抗白细胞介素2受体单抗诱导治疗.随访1年以上,观察各组术后移植肾功能、急性排斥反应发生率、受者和移植肾存活率及并发症发生率.结果 高致敏组、低致敏组和非致敏组受者术后移植肾恢复正常的时间和1年时肾小球滤过率均无明显差异;3组均未发生超急性排斥反应,急性排斥反应发生率分别为9.76％(4/41)、8.82％(9/102)和8.15％(38/466),术后1年移植肾存活率分别为97.6％(40/41)、97.1％(99/102)和98.1％(457/466),受者存活率分别为97.6％(40/41)、98.0％(100/102)和98.9％(461/466),3组间上述指标的差异均无统计学意义(P＞0.05).高致敏组的感染发生率为31.7％(13/41),明显高于低致敏组的26.5％(27/102)和非致敏组的21.6％ (101/466) (P＜0.05).结论 致敏受者肾移植前经HLA抗体检测和CDC配型,避开受者体内供者特异性抗体针对的供肾,并给予免疫诱导治疗,可以获得与非致敏受者相似的良好效果.     

肾移植受者术前测定抗HLA-IgG抗体的临床意义

目的　研究肾移植受者术前抗HLA IgG抗体水平的临床意义。 方法　采用酶联免疫吸附法 (ELISA)检测 184例肾移植受者术前抗HLA IgG抗体水平。分析抗HLA IgGI类抗体、Ⅱ类抗体阳性与急性排斥反应发生的关系。结果　肾移植受者术前抗HLA IgG抗体阴性者 15 5例 ,其中18例发生排斥反应 ,发生率 11.6 % ;抗HLA IgGⅠ类抗体阳性者 7例 ,2例发生排斥反应 ,发生率2 8.5 7% ;抗HLA IgGⅡ类抗体阳性者 9例 ,4例发生排斥反应 ,发生率4 4 .4 4 % ;Ⅰ类抗体、Ⅱ类抗体均阳性者 13例 ,8例发生排斥反应 ,发生率 6 1.5 3% ,与阴性对照组比较 ,差异有显著性 (P <0 .0 0 1)。结论　肾移植受者术前抗HLA IgG抗体阳性与术后排斥反应发生率密切相关 ,提示术前检测抗HLA IgG抗体具有重要的临床意义 ,可以预测排斥反应及指导治疗。     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

免疫吸附预防高致敏肾移植受者超急性排斥反应

目的探讨免疫吸附对高致敏‘肾移植受者超急性排斥反应的预防作用。方法对10例群体反应抗体（PRA）〉40％的‘肾移植受者术前行免疫吸附治疗，观察其超急性排斥反应发生情况及不良反应。结果10例高致敏肾移植受者均未发生超急性排斥反应，仅有2例发生急性排斥反应，并通过免疫吸附及调整免疫抑制剂得到逆转。所有受者随访至今移植‘肾功能良好，未发生排斥反应。结论免疫吸附可以安全、有效地预防高致敏人群‘肾移植术后超急性排斥反应。     

HLA配型对群体反应性抗体阳性的肾移植受者人/肾存活率的影响

目的探讨HLA交叉反应组（CREGs）配型对群体反应性抗体（PRA）阳性肾移植受者人／肾存活率的影响。方法应用美国莱姆德公司LAT1240、LM720R、SSP2LB试剂，准确检测112例PRA阳性肾移植受者体内PRA的水平及其抗体的特异性，评估其致敏状态，应用CREGs配型标准选择最匹配的供者。结果112例受者中，HLA-Ⅰ类抗体阳性43例，Ⅱ类抗体阳性39例，Ⅰ、Ⅱ类抗体均为阳性30例；HLA配型0～5个位点错配数分别为6、39、38、21、7、1例，术后移植肾发生加速性排斥反应2例、急性排斥反应18例、慢性排斥反应5例、移植肾功能延迟恢复（DGF）4例，因排斥反应导致移植肾切除1例，死亡13例（其中移植肾带功能死亡5例）。目前人存活99例，肾存活96例，5年、3年和1年肾存活率分别为86．21％、86．96％和91．96％。结论运用CREGs配型原则，能使供、受者间的HLA相配率显著提高，可减少PRA对肾移植的不良影响，提高PRA阳性受者的人／肾存活率。     

高致敏肾移植供受者的HLA配型研究

目的　探讨人类白细胞抗原 (HLA)配型在高致敏受者肾脏移植中的临床意义。　方法　对 18例高致敏受者采用酶联免疫吸附法 (ELISA)检测体内预存的群体反应性抗体 (PRA IgG)水平及其特异性 ;采用补体依赖性细胞毒试验 (CDC)和微量序列特异性引物聚合酶链反应 (Micro PCR SSP)技术进行HLA I类和II类分型。　结果　 18例高度致敏受者的PRA IgG水平为 40 %～ 96 % ,平均 5 6 % ;供受者之间按传统的HLA A、B、DR抗原错配 (MM )原则 ,0～ 1MM者 5例 (2 8% ) ,2～3MM者 13例 (72 % ) ,而按交叉反应组 (CREGs)错配原则 ,0～ 1MM者 11例 (6 1% ) ,增加了 33 % ,而2～ 3MM者仅 7例 (39% ) ;肾移植术后仅 4例发生急性排斥反应 ,排斥发生率为 2 2 % ,经OKT3 治疗后逆转。　结论　CREGs配型可显著提高供受者的HLA配合率 ,良好的HLA配型对减少高致敏受者肾移植的排斥反应、提高移植物存活率具有重要临床意义     

早期移植肾丢失引起HLA体液致敏的机制 (附3例报告)

目的探讨早期移植肾丢失引起HLA体液致敏的机制.方法采用LAT-ELISA法分别检测3例首次尸肾移植丢失的受者术前1周、术后1个月群体反应性抗体(PRA)IgG类HLA抗体水平,并分析其性质.结果1例女性受者术前1周PRA水平Ⅰ类为17.9%,其抗体特异性为B60,Ⅱ类为阴性;术后1个月PRA水平Ⅰ类为39.3%,其抗体特异性为B17,Ⅱ类为阴性.2例男性受者术前1周Ⅰ、Ⅱ类PRA为阴性(PRA＜10%).术后1个月Ⅰ类PRA水平分别为46.4%和41.7%,其抗体特异性分别为B63、B22;Ⅱ类PRA水平分别为25.0%、23.1%,其抗体特异性均为DR53.结论移植肾丢失患者术后产生抗供者特异性抗体(Ds-Ab),表明移植物是机体HLA体液致敏的重要危险因素之一.     

Utility of Intravenous Immune Globulin in Kidney Transplantation: Efficacy, Safety, and Cost Implications

Intravenous immunoglobulin preparations (IVIG) are known to be effective in the treatment of various autoimmune and inflammatory disorders into their immunomodulatory, immunoregulatory, and anti-inflammatory properties. Recently, IVIG has been utilized in the management of highly sensitized patients awaiting renal transplantation. The mechanisms of suppression of panel reactive antibodies (PRA) in patients awaiting transplantation are currently under investigation and appear to be related to anti-idiotypic antibodies present in IVIG preparations. In this review, the various immunomodulatory mechanisms attributable to IVIG and their efficacy in reducing PRAs will be described. In addition, the use of IVIG in solid organ transplant recipients will be reviewed. The adverse events, safety considerations, and economic impact of IVIG protocols for patients awaiting solid organ transplantation will be discussed.     

Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial

Reported are the reduction of anti-HLA antibody levels and improvement of transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double-blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101 adult patients with ESRD who were highly sensitized to HLA antigens (panel reactive antibody [PRA] > or =50% monthly for 3 mo) enrolled onto an NIH-sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG 2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional infusions at 12 and 24 mo after entry if not transplanted. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. However, IVIG significantly reduced PRA levels in study subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three placebo) among adherent patients with similar 2-yr graft survival rates (80% IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable transplants functioned normally with a mean +/- SEM serum creatinine of 1.68 +/- 0.28 for IVIG versus 1.28 +/- 0.13 mg/dl for placebo. Adverse events rates were similar in both groups. We conclude that IVIG is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized patients with ESRD. Transplant rates for highly sensitized patients with ESRD awaiting kidney transplants are improved with IVIG therapy.     

Successful kidney transplantation after desensitization using plasmapheresis, low-dose intravenous immunoglobulin, and rituximab in highly sensitized patients: a single-center experience

Background

For many highly allosensitized renal transplant candidates, an acceptable donor is never identified, and the patient remains on dialysis indefinitely. In an attempt to ameliorate this situation, several desensitization protocols have been developed that permit positive-crossmatch kidney transplantation. Here, we report our experiences of living donor kidney transplantation in highly sensitized patients.

Methods

We treated seven highly sensitized patients between March 2003 and September 2009. All patients underwent desensitization using pretransplant plasmapheresis (PP) and low-dose intravenous immunoglobulin (IVIG; 100 mg/kg) with rituximab (six patients) or without rituximab (one patient). Demographics, immunologic characteristics of patients, allograft function, acute rejection (AR) episodes, survival, and adverse events were evaluated.

Results

Seven patients with positive-crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Their mean age was 51.4 ± 3.3 years. The average number of human leukocyte antigen mismatchs was 3.4 ± 0.5. The mean percent PRA was 41.7% ± 6.1%. Six patients were crossmatch-positive, and one patient was crossmatch-negative but had high PRA levels. The mean follow-up period was 33.2 ± 5.4 months after transplantation. The all patients showed no AR episodes for follow-up period, and the patient and graft survival rates were 100%. The mean serum creatinine concentration at last follow-up was 0.92 ± 0.11 mg/dL.

Conclusions

Our experiences suggest that the combination of PP and low-dose IVIG with or without rituximab may prove effective as a desensitization regimen for positive-crossmatch and/or highly sensitized living donor renal transplant recipients. Further investigations are needed to evaluate the long-term clinical efficacy and safety of this approach.     

Calculated PRA: Initial Results Show Benefits for Sensitized Patients and a Reduction in Positive Crossmatches

The calculated panel reactive antibody (CPRA), which is based upon unacceptable HLA antigens listed on the waitlist form for renal transplant candidates, replaced PRA as the measure of sensitization among US renal transplant candidates on October 1, 2009. An analysis of the impact of this change 6 months after its implementation shows an 83% reduction in the number of kidney offers declined nationwide because of a positive crossmatch. The increasing acceptance and utilization of unacceptable HLA antigens to avoid offers of predictably crossmatch‐positive donor kidneys has increased the efficiency of kidney allocation, resulting in a significant increase in the percentage of transplants to broadly sensitized (80+% PRA/CPRA) patients from 7.3% during the period 07/01/2001–6/30/2002 to 15.8% of transplants between 10/1/09–3/31/10. The transplant rates per 1000 active patient‐years on the waitlist also increased significantly for broadly sensitized patients after October 1, 2009. These preliminary results suggest that ‘virtual’ positive crossmatch prediction based on contemporary tools for identifying antibodies directed against HLA antigens is effective, increases allocation efficiency and improves access to transplants for sensitized patients awaiting kidney transplantation.     

Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation.

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.     

Highly Successful and Low-Cost Desensitization Regime for Sensitized Living Donor Renal Transplant Recipients

10–30% of dialysis population awaiting renal transplantation is sensitized. Present desensitization protocols use intravenous immune globulins, rituximab, and plasmapheresis in various combinations; however, these regimens are unaffordable by many in developing countries. We tried desensitization with mycophenolate mofetil and plasmapheresis. Methods. Patients with high PRA titre (≥50%) or positive crossmatch (>10%) were treated with MMF for a month before proposed transplant and were given five sittings of plasmapheresis. Results. 11 of 12 patients had normalization of PRA/crossmatch with this regimen and were successfully transplanted. One patient lost the graft due to graft vein thrombosis, and two patients died within three months after transplant due to septicemia and pulmonary embolism, respectively, with a functioning graft. No patient, including the two who died, developed clinical rejection over a mean follow-up of 10 months (range 1–16 months). Mean serum creatinine at last follow up was 1.1 mg/dL (range 0.9–1.3 mg/dL). Conclusions. Though the number of patients studied is small, we feel that highly sensitized patients awaiting living donor renal transplant should be tried on this simple and cost-effective regime before transplant. The more aggressive and expensive approaches incorporating IVIg and rituximab should be used only if this relatively low-cost regime is unsuccessful.     

双滤过法血浆分离治疗移植肾术后排斥反应及术前高度致敏

目的探讨肾移植术后排斥反应和术前高度致敏的治疗方法。方法采用双滤过法血浆分离术（ＤＦＰＰ）治疗３６例术后排斥反应和９例术前高度致敏患者。结果２４例急性排斥中２２例逆转,１０例加速性排斥（ＡＣＲ）全部逆转,１例慢性排斥肾功能稳定,１例超急性排斥（ＨＡＲ）摘除移植肾;排斥反应采用ＤＦＰＰ治疗者其一年移植肾生存率为８４．０％。去致敏抗体者８例已接受肾移植,其中１例术后发生ＨＡＲ。结论认为ＤＦＰＰ是治疗排斥反应和预防高敏患者术后发生致敏抗体介导的ＨＡＲ和ＡＣＲ的有效方法,显著提高了排斥反应的逆转率和移植肾生存率     

Comparison of allogeneic and xenogeneic in vitro T-cell proliferative responses in sensitized patients awaiting kidney transplantation

Highly sensitized patients awaiting kidney transplantation may be potential candidates for future clinical trials using pig organ donors. Because of crossreactivity between human leucocyte antigens (HLA) and swine leucocyte antigens (SLA), such patients might have heightened T-cell responses to porcine xenoantigens. We determined whether lymphocytes from allo-sensitized patients displayed secondary (cyclosporine resistant) T-cell proliferative responses against porcine xenoantigens. Lymphocytes from six non-sensitized, seven sensitized [immunoglobulin G (IgG) panel reactive antibodies (PRA) 11 to 84%], 14 highly sensitized patients (IgG PRA > 84%) and 12 healthy individuals were tested [in the presence and absence of Cyclosporin A (CsA)] to determine their proliferative response to human (allogeneic) and to porcine (xenogeneic) stimulator cells. Lymphocytes from all study groups showed a strong proliferative response to allogeneic and xenogeneic stimulator cells with no significant difference between non-sensitized and sensitized individuals. Addition of CsA (100 and 500 ng/ml) inhibited (>90%) proliferation of lymphocytes from all non-sensitized patients to both allogeneic and xenogeneic stimulators. CsA was less effective at inhibiting proliferation of lymphocytes from sensitized patients and highly sensitized patients to allogeneic stimulators [29% (n=21) and 50% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. In contrast, cyclosporine inhibited proliferation of lymphocytes from the majority of sensitized and highly sensitized patients to xenogeneic stimulator cells [14% (n=21) and 14% (n=42) respectively were resistant to CsA inhibition (100 ng/ml)]. HLA sensitized patients awaiting renal transplantation display cyclosporine resistant proliferative T-cell responses to allogeneic stimulators but proliferative responses to xenogeneic stimulators are more amenable to suppression by CsA. This finding suggests that humoral sensitisation to HLA antigens is not necessarily indicative of a heightened in vitro T-cell response to SLA antigens.     

Desensitization strategies enabling successful renal transplantation in highly sensitized patients

Abstract:  Currently, the number of highly sensitized patients awaiting a renal transplant is increasing on the waiting lists of different organ exchange organizations. Due to the presence of antibodies against a broad variety of human leukocyte antigen (HLA) specificities, highly sensitized patients have a markedly reduced chance of receiving a crossmatch-negative organ. It has long been recognized that hyperacute rejection is associated with the presence of donor-specific anti-HLA antibodies at the time of transplantation. Meanwhile treatment protocols have been developed to achieve successful transplantation across antibody barriers. Therefore, the presence of donor-specific anti-HLA antibodies and a positive serological crossmatch are no longer considered as an absolute contraindication to renal transplantation. Mainly, two desensitization protocols have been established in order to overcome a positive crossmatch or to enhance the chance of highly sensitized patients to receive a crossmatch-negative organ: high-dose intravenous immunoglobulin (IVIg) or low-dose IVIg in combination with plasmapheresis. Herein, we summarize the characteristics of these two treatment regimes along with other alternative approaches that are currently used for the management of kidney graft recipients with broad alloantibody reactivity against potential kidney donors.