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1.
Patients undergoing ABO-incompatible kidney transplantation must have their anti-donor blood-type antibody titer (ADBT) reduced to below 1:16 by using either plasma-exchange (PEX) or double filtration plasma exchange (DFPP) before they can safely undergo a transplantation. The ADBT can be reduced to under 1:16 in most cases; however, some cases (non-responders) do not respond to PEX or DFPP treatment. To enable kidney transplantations to be performed in non-responders, we developed a new preconditioning regimen consisting of anti-CD20 monoclonal antibody (rituximab) infusions, a splenectomy, and DFPP. Four non-responders were infused with rituximab at a dose of 375 mg/m(2) weekly for 3-4 wk and splenectomized 1 or 2 wk before transplantation. Four to five DFPP-sessions were then performed after the splenectomy. Using this preconditioning regimen, the ADBT was reduced to below 1:16, enabling kidney transplantations to be successfully performed in all patients. After the kidney transplantation, no episodes of humoral rejection were observed, and only one episode of cellular rejection was encountered. The cellular rejection was associated with a reduction in immunosuppressant administration because of CMV infection that occurred 80 d after the kidney transplantation. The renal allografts were functioning well in all patients after a mean follow-up period of 390 d. No serious complications or side effects were encountered. We have developed a new preconditioning regimen that enables PEX and DFPP non-responders to undergo ABO-incompatible kidney transplantations.  相似文献   

2.
A 24-yr-old man was admitted to our hospital for ABO-incompatible kidney transplantation. His blood type was O, and the donor's (his father's) blood type was B. The recipient had pancytopenia, splenomegaly, splenorenal shunts and esophageal varices due to congenital hepatic fibrosis. Therefore, if splenorectomy was performed, the blood pressure of the portal vein and the growth of esophageal varices were predicted. Eventually, in return for splenectomy, anti-CD20 monoclonal antibodies (rituximab), intravenous immunoglobulin and plasmapheresis was performed for additional immunosuppression. Because of progression of pancytopenia, we had to decrease the dose of mycophenolate mofetil and gave up on using deoxyspagalin. Nevertheless the serum creatinine level decreased and remained in the 1.6 to 1.8 mg/dl range.  相似文献   

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4.

Background

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy.

Methods

Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12).

Results

The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant).

Conclusions

We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.  相似文献   

5.
BACKGROUND: ABO-incompatible living-donor liver transplantation (LDLT) requires a reduction of the anti-ABO antibody titer to <16 before transplantation, which is usually achieved by pre-operative plasma exchange (PE) or double-filtration plasmapheresis. ABO-incompatible transplantations have been performed after a splenectomy with heavy drug immunosupression plus B-cell-specific drugs. Here, we evaluated a pre-transplantation infusion protocol with an anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible LDLT. METHODS: Between March 2002 and December 2005, 73 adult patients underwent LDLT without retransplantation in our institution. Among these cases, 57 were ABO-identical, 11 were ABO-compatible and five were ABO-incompatible. The rituximab infusion protocol consisted of a weekly infusion of rituximab (375 mg/m(2)) for three wk, which was administered to three of the five ABO-incompatible LDLT patients. All three patients underwent a pre-operative PE, as well as a splenectomy during the operation. A triple immunosuppression protocol of tacrolimus, low-dose steroids and mycophenolate mofetil (1500 mg/d) was administered post-operatively. In addition, the patients received a continuous intra-arterial infusion of prostaglandin E(1) and methylprednisolone, and a continuous intra-portal infusion of a protease inhibitor for three and two wk after transplantation, respectively. RESULTS: After the first rituximab infusion, the peripheral blood CD19(+) B cell count rapidly decreased to <1%. All three patients treated with rituximab subsequently received an ABO-incompatible LDLT, with donor/recipient blood groups of B/O, A(1)/B and A(1)/O. In two cases, the ABO-antibody level transiently increased post-operatively, then decreased and remained low. Rituximab infusion therapy did not develop any direct side effect except for mild allergic reaction to the first infusion, but post-operatively all three patients suffered a cytomegalovirus and were successfully treated with ganciclovir, and one patient had a MRSA-positive intra-abdominal abscess. Two patients are currently alive at 20 and 18 months respectively, and show normal graft-liver function. But one patient died of sepsis because of intra-abdominal abscess. CONCLUSIONS: Although the protocol of rituximab administration is a conventional and safe regimen with no major side effects, the development of a new protocol is needed for prevention of the infection with bone suppression.  相似文献   

6.
Abstract: Background: In Japan, ABO‐incompatible (ABO‐I) kidney transplantation began in 1989; these transplantations have flourished because of the lack of cadaveric donors, and more than 600 cases were performed up to 2004. Splenectomy has been considered to be necessary for successful ABO‐I kidney transplantation, and the majority of pre‐conditioning protocols include splenectomy in Japan. However, we have lost some grafts due to antibody‐mediated rejection (AMR) accompanying explosive elevation of anti‐A/B antibody (Ab) titer even though the patients had a low pre‐operative Ab titer. Patients and methods: We utilized two doses of anti‐CD20, rituximab, simply combined with mycophenolate mofetil (MMF)/low‐dose steroid desensitization started 1 month before surgery in ABO‐I kidney transplantation. Two sessions of pre‐operative Ab removal by double filtration plasmapheresis or plasma exchange were carried out. We performed six ABO‐I kidney transplantations without splenectomy. Anti‐A/B Ab titers were more than 16 to 32 times before treatment. We did not plan any post‐operative repeated Ab removal or intravenous immunoglobulin G (IVIG). Results: Pre‐operative anti‐A/B Ab titers were successfully reduced to less than eight times in all cases. Except for one case in which we had to remove the graft due to aspiration pneumonia and methicillin‐resistant staphylococcus epidermidis (MRSE) sepsis, the other five cases did not experience antibody‐mediated rejection (AMR). An additional session of post‐operative Ab removal and/or IVIG was not necessary. In all patients, B cells (CD19+, CD20+, CD21+) and activated T cells (CD25+) were selectively suppressed, although CD3+, CD4+and CD8+ cell populations remained stable, thus we call our protocol “pinpoint targeted immunosuppression.” Plasma immunoglobulin level was also successfully suppressed, especially after 6 weeks of surgery. Conclusion: Anti‐CD20/MMF desensitization is safe and allows successful ABO‐I kidney transplantation without splenectomy.  相似文献   

7.
In patients with fulminant liver failure requiring emergency liver transplantation, the only donor organ that becomes available may be ABO incompatible. The risk of graft failure because of antibody-mediated acute rejection is high, but can be reduced by various means. We reported a deceased donor ABO-incompatible liver allograft recipient who was treated with antigen-specific immunoadsorption in combination with anti-CD20 monoclonal antibody and conventional plasmapheresis and immunosuppression. The patient was a 33-yr-old male with blood group A who presented with subacute liver failure of unknown aetiology and received a blood group AB liver graft. Pretransplant he underwent plasmapheresis and received one dose of rituximab. The immunosuppressive regimen consisted of methylprednisolone, tacrolimus and mycophenolate mofetil. Despite regular post-operative plasmapheresis sessions, anti-B antibody titres increased. Antigen-specific immunoadsorption with depletion of anti-B antibodies was performed from day nine to day 17. Thereafter, anti-B IgM and IgG antibody titres remained low. After one month the patient was reoperated with hepaticojejunostomy because of bile duct necrosis and with reconstruction of a stenotic hepatic artery. A mild rejection was successfully treated with methylprednisolone four months post-transplant. At six months post-transplant there was a stricture of the biliary-enteric anastomosis, but the graft was well functioning. We conclude that antigen-specific immunoadsorption can be an important adjuvant therapy to control recipient anti-A/B antibody levels and prevent acute rejection in ABO-incompatible deceased donor liver transplantation.  相似文献   

8.
Fulminant hepatic failure continues to be a challenge to hepatologists and surgeons. Because of the rapid deterioration in the clinical condition of patients with fulminant hepatic failure and the scarcity of available grafts, an ABO-incompatible liver donor may be the only choice for a patient with life-threatening hepatic insufficiency. Here, we report a patient with fulminant hepatic failure who received an ABO-incompatible liver transplantation who was treated with pre- and posttransplantation double-volume total plasma exchange, splenectomy, and triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisone) in July 2003. At 26 months' follow-up, the patient's postoperative course has been uneventful. Using protocols aimed at removing existing isohemagglutinins and reducing further antibody production, ABO-incompatible liver transplantation may be performed as a life-saving procedure in patients with fulminant hepatic failure.  相似文献   

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BACKGROUND: Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. METHODS: We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). RESULTS: Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. CONCLUSIONS: Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.  相似文献   

11.
BACKGROUND: Due to the growing organ shortage in the Balkans and still underdeveloped cadaver transplantation, we started accepting living expanded criteria renal donors including elderly, marginal and unrelated donors (spouses, etc). The ABO-incompatible renal transplantation was initiated last year. The first two successful cases are presented. METHODS: A 40-yr-old mother (blood group A1B) and a 57-yr-old husband (blood group B) were considered as suitable donors for an 18-yr-old daughter (blood group B) and a 52-yr-old wife (blood group O). Both the recipients had a relatively long dialysis treatment before the surgery. The anti-A1 and anti-B titer of isoaglutinins was 1 : 64 in both the recipients before the procedure. A routine laparoscopic splenectomy was performed 40 and 45 days before the transplantation, without any complications. In the 10 days pre-conditioning period, rituximab was administered in a single dose of 375 mg/m2. At the same time four to five plasmaphereses were performed to reduce the isoaglutinins to below 1 : 4. On the last night before the surgery intravenous immunoglobulin (IVIG) in a dose of 0.5 g/kg/bw was administered. Standard induction and maintenance therapy was introduced (Dacllizumab, CyA-Neoral, MMF and steroids) according to the accepted policy in our transplant center. The routine plasmaphereses were performed in the first 2 weeks after transplantation to keep the isoaglutinins titer below 1 : 8. RESULTS: Ten and 6 months after the surgery both recipients are doing well. Their graft function remains stable (actual serum creatinin 140 and 230 microm/L, respectively). In the 1 month protocol biopsy a subclinical cellular and mild vascular rejection occurred, and both recipients were treated by steroid pulse therapy. One to two additional plasmaphereses were performed. The regularly monitored anti-A1 and anti-B isoaglutinins titer was kept below 1 : 8 during a period of follow-up. CONCLUSION: The first short-term results fully justify the ABO-incompatible living renal transplantation. The authors consider ABO-incompatible transplantation as a safe and promising procedure which may, together with expanded criteria living donors, ameliorate the actual donor shortage in the region.  相似文献   

12.
目的 探讨抗CD25单抗联合血浆分离在群体反应性抗体(PRA)阳性的高敏肾移植受体中的应用价值。方法 在41例PRA平均为52.2%的高敏肾移植受体中,24例仅用双滤过法血浆分离(DFPP)预处理(对照组),17例在DFPP处理的基础上加用两个剂量的抗CD25单抗诱导治疗(治疗组),比较两组急性排斥反应的发生率、严重程度和逆转情况、1年人/肾存活率以及并发症的发生。结果 治疗组仅2例(11.8%)发生急排,分别为IA和ⅡJ3级,对照组1例(4.2%)发生超排,10例(41.7%)发生急排,ⅡA级以上有6例,2组差异有显著性意义(P=0.039)。一年人/肾存活率治疗组为100%/94.1%,对照组为100%/91.7%,两组并发症无明显差异。结论PRA阳性的高敏肾移植受体在DFPP基础上应用抗CD25单抗能显著降低急性排斥的发生,减轻排斥反应的严重程度,获得满意的1年人/肾存活率。  相似文献   

13.
A 21-year-old man with bilateral hypoplastic kidneys underwent laparoscopic splenectomy and ABO-incompatible living renal transplantation. After the splenectomy, pancreatic leak occurred and it caused intra-abdominal bleeding on the 10th and 16th postoperative day, so emergency operations were performed. Then the graft function had become stable and he was discharged on the 75th postoperative day. Although intra-abdominal bleeding due to pancreatic leak often causes a fatal condition, he was successfully treated by suppression of pancreatic external secretion using octreotide and appropriate drainage.  相似文献   

14.
15.
BACKGROUND: Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. PATIENTS AND TREATMENT PROTOCOL: Recipients were blood group O (n = 12), A (n = 1) and B (n = 1). Donors were A1 (n = 2), A2 (n = 3), A2B (n = 1) and B (n = 8), and all were secretor positive. Anti-human leukocyte antigen (HLA) Ab panel reactivity was negative in all recipients except one. All recipients were pre-treated with 3 to 6 IA sessions, using A or B carbohydrate antigen columns, until their anti-A1/B RBC panel indirect antiglobulin test (IAT) titers were < or =8. CDC crossmatch was negative in all cases. Recipients received preoperative mycophenolic acid, and steroids/tacrolimus were started at transplantation. No splenectomy was performed. Eight recipients received one dose of anti-CD20 mAb (rituximab, 375 mg/m2) pre-operatively and 11 recipients had postoperative protocol IA. RESULTS: In the initial protocol, anti-CD20 mAbs were used only for recipients receiving A1 grafts. One B graft (HLA-identical donor, 84% panel reactivity) was lost in a severe anti-B Ab-mediated acute rejection. Subsequently, the protocol included anti-CD20 for recipients of both A1 and B grafts and postoperative protocol IA to all recipients. The subsequent 10 grafts had excellent function, giving a total graft survival of 13/14 (observation range 2 to 41 months). At 1 yr, mean serum creatinine was 113 micromol/l (n = 8) and mean glomerular filtration rate was 55 ml/min/1.73 m2 (range 24 to 77). In the remaining five cases, with less than 1 yr follow up, mean serum creatinine was 145 micromol/l at 2 to 9 months follow up. Pre-IA anti-A/B titers were in the range of 2 to 32 (NaCl technique) and 16 to 512 (IAT). More than 90 IA sessions were performed in 14 recipients without any significant side effects. Recipient anti-A/B titers returned after transplantation to pre-IA levels or slightly lower. Postoperative renal biopsies were performed in 10 patients. In the 13 patients with long-term function, one patient experienced cellular rejection (Banff IIB) at 3 months without anti-B titer rise. This rejection was concomitant with low tacrolimus plasma levels and was easily reversed by steroids. In 8 of 10 cases, C4d staining was positive in peritubular capillaries. CONCLUSION: Blood group ABO-incompatible LD renal transplantation using A and B carbohydrate-specific IA and anti-CD20 mAbs has excellent graft survival and function.  相似文献   

16.
It is more difficult to control humoral rejection in living donor liver transplantations (LDLT) across the ABO blood group barrier than in matched or compatible combinations. We achieved excellent results in ABO-incompatible transplantation with novel immunosuppressive regimens and plasma exchange (PE). Among 82 LDLT were 10 cases of ABO-incompatible recipients, including three who were administered rituximab for rescue or prophylactic therapy. Pretransplantation PE was performed as necessary to maintain hemagglutinin titers below 1:16 and posttransplantation PE was performed when there were signs of hyperacute rejection associated with high titers. Induction immunosuppression consisted of FK506, steroid, mycophenolate mofetil (MMF), and rituximab. The first patient was administered rituximab with deoxyspergualin (DSG), steroid pulse therapy, and PE on postoperative day (POD) 7, because of biopsy-proven humoral acute rejection. The titers and LFTs improved drastically. The second and third patients were administered rituximab just after the operation with other routine immunosuppressants for prophylaxis of hyperacute rejection. The second patient showed a slight deterioration in LFTs with an elevated titer, which normalized after steroid pulse therapy and PE. The third patient had no episodes of rejection. At present, that is 27, 17, and 6 months after the operations respectively, the 3 transplant recipients are in stable condition.  相似文献   

17.
In Japan, living donor kidney transplantation accounts for about 80% of all kidney transplants. This is in contrast to the United States and Europe, where transplantation of organs from cadaveric or brain-dead donors is more common. This study analyzed the results of 5 years of experience with tacrolimus in Japan, focusing on the efficacy of the drug in improving patient and graft survival in patients who underwent transplantation with ABO-incompatible kidney grafts. Of the 1542 evaluable patients, 1281 patients received grafts from living donors. Of these, 177 patients received kidneys from ABO-incompatible donors and 981 patients received kidneys from ABO-compatible donors. Graft survival rates in ABO-incompatible recipients ranged from 90.7% at 1 year to 80.5% at 5 years. Subsequent graft survival rates in ABO-compatible recipients were 98.1% and 92.9%, respectively (P < .001 between groups). Patient survival rates at 5 years were 93.2% in ABO-incompatible recipients and 98.1% in ABO-compatible recipients. The rejection rate for kidneys from ABO-compatible donors was 27.8%, while for ABO-incompatible donors the rejection rate was 45.2%. The excellent outcome from this study demonstrates that even suboptimal ABO-incompatible donors can be used successfully as a source of kidneys when using tacrolimus as the immunosuppressive regimen. This may go some way to addressing the shortage of kidney donors in Japan.  相似文献   

18.
BACKGROUND: CD40-CD154 pathway blockade by anti-CD154 monoclonal antibodies (mAbs) significantly prolongs allograft survival in nonhuman primates. However, thromboembolic complications have prevented clinical application. Thus, blockade of the counter molecule by a novel fully human anti-CD40 mAb, 4D11, is an attractive alternative. METHODS: Kidney transplantations were performed between outbred cynomolgus monkeys (stimulation index >3 in a mixed lymphocyte reaction). The animals were divided into five groups: nontreatment control (Group 1, n=3), 10-week treatment with either 10 mg/kg (Group 2, n=3), 20 mg/kg (Group 3, n=3), or 40 mg/kg (Group 4, n=1), and 4-week treatment (Group 5, n=1 each) with 10 mg/kg, 20 mg/kg, or 40 mg/kg followed by monthly administration. Graft survival, biochemistry, complete blood counts, lymphocyte phenotypes, blood drug levels, antidonor and antidrug antibodies, and renal histology were examined. RESULTS: Survival (days) was as follows: Group 1 (5, 6, 7), Group 2 (150, 108, 108), Group 3 (84, 108, 379), Group 4 (147), and Group 5 (147, 102, 112). Two animals in Group 3 with normal graft function were killed upon development of hydronephrosis and cerebral infarction. B lymphocytes fell to one-third of the preoperative value at 4 weeks after transplantation in all animals. Antidonor antibodies developed in most of the animals after stopping drug treatment or at the time of death. No animals except for one formed anti-4D11 antibody. CONCLUSION: 4D11 appears to be a promising agent for antirejection treatment in clinical organ transplantation.  相似文献   

19.
A 22-year-old patient whose primary kidney disease was focal segmental glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57 g/24 h) immediately after a haploidentic living donor kidney transplantation despite pre-operative plasmapheresis. The immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10 plasmapheresis sessions in the first 3-week post-transplantation. In addition, he received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15. Proteinuria decreased below nephrotic range at day 14 and serum creatinine returned progressively to normal values. A short course of oral ciclophosphamide (100 mg/j) was administrated between days 22 and 40 and three additional plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining sustained full remission of the nephrotic syndrome (NS) and excellent graft function, which persists over 2 years after transplantation. No notable adverse events related to RTX or plasmapheresis were observed. This case suggests that RTX associated with plasmapheresis may be an effective treatment of recurrent NS because of FSGS.  相似文献   

20.
A 39-yr-old Japanese man underwent living related kidney transplantation. Because the graft was ABO-incompatible, he was treated with double filtration plasmapheresis before transplantation and his immunosuppressive therapy was stronger than usual. However, immunoglobulin A nephropathy, accompanied by cellular crescents and necrotizing lesions, developed after 18 months. To our knowledge, the association of IgA nephropathy with ABO-incompatible kidney transplantation has not been reported previously.  相似文献   

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