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1.
ABO-incompatible (ABOI) living donor kidney transplantation has become a well-accepted practice with standard protocols using perioperative antibody-depleting therapies to lower blood group titers to an acceptable threshold for transplantation. However, a subset of patients will experience accelerated antibody-mediated rejection (AMR) after ABOI kidney transplantation and require aggressive intervention to prevent allograft loss. Here in we report the successful use of terminal complement inhibition with eculizumab to rescue an ABOI kidney allograft with accelerated AMR refractory to salvage splenectomy and daily plasmapheresis. This case emphasizes the fact that, despite close postoperative surveillance and aggressive intervention, graft loss from accelerated AMR after ABOI kidney transplantation remains a very real risk. Eculizumab may offer a graft-saving therapeutic option for isolated cases of severe AMR after ABOI kidney transplantation refractory to standard treatment.  相似文献   

2.
This is a case report of a living related donor kidney transplantation using basiliximab induction and maintenance immunosuppression with cyclosporine, mycophenolate sodium, and steroid. On the second posttransplant day, the patient developed acute antibody-mediated rejection, which was treated with plasmapheresis and intravenous immunoglobulin (IVIG). Five days later, the graft had still not responded to the treatment. Another biopsy revealed additional acute cellular rejection (Banff IIA). As alemtuzumab can rapidly deplete T and B lymphocytes, monocytes, and natural killer cells, the patient was treated with alemtuzumab (30 mg subcutaneously) together with methylprednisolone (500 mg) and two more plasmaphereses. The kidney graft responded within 48 hours, producing more than 4 L of urine per day. The total lymphocyte decreased from 530/μL to 50/μL remaining in the 50 to 220/μL range. The patient received valgancyclovir and cotrimoxazole as infection prophylaxis. The kidney graft responded well to the rescue treatment and the patient was discharged with a serum creatinine of 1.1 mg/mL and has been uneventfully followed in the outpatient clinic for 8 months. Today, with the potent, effective, and selective immunosuppressive regimens, the rate and severity of acute cellular rejection in kidney transplantation has decreased in most centers. However, the rate of acute antibody-mediated rejection has increased to levels greater than those of acute cellular rejection in many centers. Acute antibody-mediated rejection is more difficult and expensive to treat successfully. The treatment of acute antibody-mediated rejection included plasmapheresis and IVIG. Herein we have reported a case of kidney transplantation simultaneously developing acute antibody-mediated and acute cellular rejection; the patient was successfully treated with alemtuzumab.  相似文献   

3.
The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.  相似文献   

4.
BackgroundHeparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin. Additionally, although heparin can affect kidney transplantation, there only have been a few reports on this condition. Here, we report a case wherein surgery was safely performed with preoperative plasmapheresis in a patient with HIT.Case PresentationThe patient was a 48-year-old woman who was on dialysis because of immunoglobulin A nephropathy. Immediately after the initiation of dialysis, the patient experienced repeated arteriovenous fistula occlusion and thrombocytopenia and had a positive HIT antibody test result. Subsequently, she received an ABO-incompatible living-donor kidney transplantation from her spouse. The surgery was performed without using anticoagulants because HIT antibodies disappeared with preoperative plasmapheresis. Eighteen months after surgery, her kidney function remained stable, and there was no recurrence of HIT.ConclusionPreoperative plasmapheresis is useful for patients with HIT.  相似文献   

5.
《Transplantation proceedings》2019,51(8):2602-2605
BackgroundRabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation.MethodsBetween April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function.ResultsA total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration.ConclusionsrATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.  相似文献   

6.
HLA antibodies usually recognize epitopes rather than antigens. This case report reveals that acute antibody-mediated rejection (AMR) that occurred in a kidney transplant recipient with low-level donor-specific antibodies (DSAs) could be explained by shared epitope. A 39-year-old woman received a first kidney transplant from a deceased donor (HLA-DRB1*11:06, *12:02, DRB3*02:02, *03:01). She developed acute AMR confirmed by kidney biopsy on day 4 after transplantation. Antibody testing with pretransplant serum showed anti-DR11 DSA below cutoff level (mean fluorescence intensity [MFI], 702; cutoff >1,000). However, high-level DSAs were detected on day 5 after transplantation (anti-DR11 MFI, 8,531; anti-DR12 MFI, 3,146). We hypothesized that the sharp rise in DSA levels was a result of anamnestic response with donor-antigen sensitization that occurred during pregnancy. High-resolution HLA-DR typing of her husband showed HLA-DRB1*03:01, *15:02:01, DRB3*02:02, DRB5*01:02. No sharing between donor HLAs eliciting reactive antibodies and her husband's HLAs was detected. Nevertheless, we speculated that shared epitope, not antigen, was the cause of allosensitization. To identify the shared epitope recognized by patient's antibodies, we used HLAmatchmaker, a computer algorithm that considers small configurations of polymorphic residues referred to as eplets as essential components of HLA epitopes for analysis. The results showed that 149H, which was the eplet shared by HLA-DRB1*03:01 (from her husband) and DRB1*11:06, DRB1*12:02, DRB3*03:01 (from donor), was the most prevalent eplet on DRB1 reactive alleles in Luminex assay. In conclusion, pretransplant low-level DSAs can induce AMR early after transplantation as a result of shared epitopes with a previous immunizer.  相似文献   

7.
《Transplantation proceedings》2019,51(5):1382-1386
BackgroundRituximab (RIT) is effective as a part of the desensitization therapy before ABO-incompatible kidney transplantation (ABOi-KTx), and a single dose of RIT at 375 mg/m2 or less is recommended. However, adequate RIT dose recommendations have not yet been established for individual recipients. Therefore, we evaluated the relationship between the proportion of B cells in peripheral blood and acute antibody-mediated rejection (AAMR).MethodsForty-four consecutive ABOi-KTx recipients were enrolled in this retrospective study. Before transplantation, subjects were treated with RIT at various doses, ranging from 65 to 400 mg/body (46–263 mg/m2), followed by plasmapheresis and intravenous immunoglobulin as a desensitization therapy. The percentage of CD19+ cells in the total peripheral blood lymphocytes population (%CD19) was determined the day before transplantation. Transplant recipients were divided into 2 groups according to pretransplant %CD19, as follows: low %CD19 group, ≤ 1.2% (n = 35) and high %CD19 group, > 1.2% (n = 9). The relationship between %CD19 and incidence of AAMR was evaluated, and the predicting factors for AAMR incidence were determined by univariate and multivariate analyses.ResultsThe incidence of AAMR was significantly higher in the high %CD19 group than in the low %CD19 group (44.4% vs 5.7%, P = .006). Furthermore, multivariate analysis showed that %CD19 > 1.2% was the only independent factor to predict AAMR, with an odds ratio of 14.31 (P = .038).ConclusionHigh %CD19 values after rituximab administration in ABOi-KTx recipients implies insufficient depletion of B cells, which can lead to AAMR.  相似文献   

8.
《Transplantation proceedings》2022,54(9):2570-2577
BackgroundOne of the most important possible complications determining long-term graft survival after kidney transplant is antibody-mediated rejection (ABMR). The criterion standard approach to recognize ABMR is currently the kidney biopsy with histopathologic analysis. However, this test has limitations because of difficulties in timing of sampling, the evaluability of histology because of the questionable representativeness of specimens, and the limited number of this intervention. Hence, new reliable, noninvasive biomarkers are required to detect the development of ABMR in time.MethodsIn this study, we analyzed the clinical data of 45 kidney transplant patients (mean age of 44.51 years, 20 male and 25 female subjects). These participants were recruited into 5 subcohorts based on their clinical status, histologic findings, and level of donor-specific anti-HLA antibodies. Circulating microRNAs (miR-21, miR-181b, miR-146a, miR-223, miR-155, miR-150) in plasma samples were quantified by quantitative polymerase chain reaction and their levels were correlated with the clinical characteristics in different subgroups.ResultsThe relative expression of plasma miR-155 (P = .0003), miR-223 (P = .0316), and miR-21 (P = .0147) were significantly higher in patients who had subsequent histology-approved ABMR with donor-specific anti-HLA antibody positivity (n = 10) than in the “triple negative” group (n = 21), and miR-155 showed the highest sensitivity (90%) and specificity (81%) to indicate ABMR development based on receiver operating characteristic analysis.ConclusionsAccording to our preliminary data, plasma miR-155, miR-21, and miR-223 can indicate the development of ABMR after kidney transplant in correlation with classic clinical parameters. However, future studies with larger number of participants are necessary to further evaluate the diagnostic properties of blood miRNAs in prediction of this life-threatening condition.  相似文献   

9.
An 82-year-old man with a history of renal transplantation 14 years earlier presented with acute obstructive renal failure secondary to inguinal herniation of the urinary bladder complicated by ureteroneocystostomy entrapment. After percutaneous nephrostomy tube and endoscopic stent placement, the bladder was reduced and the hernia repaired with the use of a preperitoneal mesh. The postoperative course was uneventful and the renal function returned to normal. Inguinal herniation of the transplant ureter is a rare cause of hydronephrosis, but it has been described in the literature. Bladder hernias do usually not cause urologic complications in the nontransplanted patient, but they can present as an emergency after renal transplantation.  相似文献   

10.
ObjectiveActive antibody-mediated rejection (aABMR), particularly late aABMR, remains a major challenge for long-term renal allograft survival. This single-center retrospective study aimed to compare clinical features between early vs late aABMR and to identify risk factors for allograft failure among patients with aABMR.MethodForty-one patients diagnosed with aABMR at our hospital were included and were divided into 2 groups: early aABMR (≤6 months; n = 10) vs late aABMR (>6 months; n = 31) based on the time from transplant to diagnosis. Their clinical and pathologic data were compared. This study was performed in compliance with the Helsinki Congress and the Declaration of Istanbul.ResultsOf 10 patients with early aABMR, none had allograft failure, whereas 8 of 31 patients with late aABMR had developed allograft failure at the time of follow-up (25.8%). At the time of biopsy, patients with early aABMR had higher positive grade in urine occult blood test than patients with late aABMR (P = .01); however, the late aABMR group displayed more intensive interstitial fibrosis and tubular atrophy (P = .03) and more frequent HLA-DQ-type donor-specific antibodies. Interestingly, donor-specific antibody conversion from positive to negative was not associated with C4d grade but was correlated with time from transplant to biopsy. Multivariate Cox regression analysis indicated that high levels of serum creatinine or proteinuria and concomitant T-cell-mediated rejection were independent risk factors for allograft failure in patients with aABMR.ConclusionThese data not only confirm that early aABMR has better clinical outcomes than late aABMR but highlight the importance of early diagnostic biopsy and early therapeutic interventions in ABMR, particularly in patients with high levels of serum creatinine or proteinuria in the early posttransplant phase.  相似文献   

11.
Antibody-mediated rejection (AMR) generally occurs in highly sensitized patients. A pilot study was performed on 7 consecutive patients with AMR to assess the efficacy of high-dose intravenous immunoglobulin (IVIG; 2 g/kg) + rituximab (RTX; 375 mg/m2) without plasmapheresis. After a 24-month follow-up, 1- and 2-year allograft survivals were 86% and 58%, respectively. C4d became negative in 1 patient posttreatment. Donor-specific antibody (DSA) titers decreased to less than 1:4 in 2 cases. There were 4 infectious complications and 1 case of aseptic meningitis followed by cranial nerve VI palsy. The average hospital charge for 1 administration of IVIG + RTX, including hospital stay and renal biopsy expenses, was approximately $49,000. A combination of IVIG + RTX in late AMR may be beneficial but is an expensive treatment approach for selected renal transplant patients.  相似文献   

12.
BackgroundInduction therapy improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the incidences of antibody-mediated rejection (AMR) and acute cellular rejection (ACR) as well as graft and patient outcomes in KTRs who underwent induction with alemtuzumab versus rabbit-antithymocyte globulin (r-ATG).MethodsThis was a single-center retrospective study involving patients who underwent kidney transplantation between January 2009 and December 2011 after receiving induction therapy with either alemtuzumab or r-ATG. Maintenance immunosuppression included tacrolimus and mycophenolate mofetil with early steroid withdrawal. Acute rejection was diagnosed using allograft biopsy.ResultsAmong the 108 study patients, 68 received alemtuzumab and 40 got r-ATG. There was a significantly higher incidence of AMR (15% vs 2.5%; P = .008) and similar incidence of ACR (4.4% vs 10%; P = .69) for alemtuzumab versus r-ATG groups. One-year serum creatinine levels (l.68 ± 0.8 mg/dL vs 1.79 ± 1.8 mg/dL; P = .66) as well as graft (91.1 ± 3.5% vs 94.5 ± 3.8%; P = .48) and patient (93.8 ± 3.0% vs 96.4 ± 3.5%; P = .92) survivals were similar for the alemtuzumab versus the r-ATG groups.ConclusionOur study showed a higher incidence of AMR and similar incidence of ACR in KTRs who underwent induction with alemtuzumab compared with those who received r-ATG and were maintained on tacrolimus and MMF. This was despite a lower HLA mismatch in the alemtuzumab group. One-year graft survival, patient survival, and allograft function were similar. Inadequate B-cell suppression by alemtuzumab as well as altered phenotypic and functional properties of repopulating B cells could be contributing to heightened risk of AMR in these patients.  相似文献   

13.
14.
Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab.A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation. At 1 month after transplantation, a protocol biopsy revealed positive granular staining of IgG, C4d, and PLA2R on glomerular capillaries (GCs) without any abnormalities on light microscopy (LM). Although the patient had low-level proteinuria, recurrent MN was suspected based on the positive PLA2R staining; he was treated with an angiotensin receptor blocker and a single dose of 200 mg rituximab. However, proteinuria gradually increased to 877 mg/d. At 21 months after transplantation, a graft biopsy revealed spikes along the outer aspects of GC on LM, with stronger staining for PLA2R than that at 1 month after transplantation. A single dose of 500 mg rituximab was added, which effectively reduced proteinuria, and clinical remission continued until 3 years after transplantation. The latest graft biopsy showed reduced staining of PLA2R. The disease activity and therapeutic effect were well-reflected in the intensity of PLA2R staining.An approach intending an early diagnosis by protocol biopsy using PLA2R immunostaining is made and early treatment with rituximab will help reduce the risk of kidney graft loss due to recurrent primary MN.  相似文献   

15.
目的高选择性蛋白酶体抑制剂硼替佐米,可特异性清除体内活化的浆细胞,对肾移植后抗体介导的排斥反应(antibody-mediated rejection,AMR)具有重要治疗作用。总结本院首例硼替佐米(bortezomib)治疗AMR的临床资料,为AMR治疗提供新的思路。方法 1例二次肾移植患者,移植后肌酐恢复到正常值,移植后20天出现急性排斥反应,恢复透析。活检病理证实为细胞性和抗体介导的混合性排斥反应。应用硼替佐米[第1天(1.3mg/m2)、第4天(1.0mg/m2)、第8天(1.0mg/m2)]同时联合甲泼尼龙250mg/次和双膜法血浆置换。观察T淋巴细胞亚群、CD139和CD19表达、二次病理活检,群体反应性抗体及血肌酐等变化。结果硼替佐米应用后随访31个月,各种指标变化:1血肌酐恢复并稳定在140umol/L左右;2PRA由最高66.7%,下降至0;3浆细胞表达在第1剂硼替佐米后先明显下降后反弹升高;4病理穿刺检测:C4D染色由强阳性变为阴性,细胞性排斥反应由ⅡA变为可疑;5出现血小板移抑制、低血压、3级周围神经病变等。结论硼替佐米可清除体内活化的浆细胞,对肾移植术后抗体介导的排斥反应的治疗具有良好的临床疗效。为肾脏移植后抗体介导的排斥反应的治疗提供一种新的治疗思路。  相似文献   

16.
Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.  相似文献   

17.
《Transplantation proceedings》2022,54(6):1551-1553
BackgroundPatients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection.Case ReportA 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable.ConclusionLiving kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered.  相似文献   

18.
Spontaneous pneumomediastinum is a rare condition with nonspecific signs and symptoms. A 39-year-old underwent cadaver kidney transplantation. After an uncomplicated operation, progressive dyspnea of unknown origin developed. Findings at chest radiography suggested pneumomediastinum, which was confirmed at computed tomography. Esophageal or tracheal injury was ruled out. The rapidly developing atelectasis of the left lung necessitated urgent bronchoscopy, which revealed occlusion of the left main bronchus. After removal of the occluding mucus plug, the clinical symptoms immediately improved, and the spontaneous pneumomediastinum resolved within 3 days. Asymptomatic increase in airway secretions in patients receiving peritoneal dialysis may result in mucus plug formation during general anesthesia, which can cause spontaneous pneumomediastinum.  相似文献   

19.

Objective

Over the past decade, antibody-mediated rejection (AMR) continues to be recognized as one of the major obstacles in cardiac transplantation, yet its clinical outcome has been reported only in small series studies. This investigation reviews our experience in treating 11 patients with AMR after heart transplantation.

Methods

We retrospectively analyzed a total of 11 patients who underwent cardiac transplantation from 2004 to 2012 at a single medical institute. The diagnosis of AMR was made according to criteria set by the International Society for Heart and Lung Transplantation (ISHLT) 2011 working formulation.

Results

The average age among the 11 patients was 50.4 ± 16.9 years. The overall mortality rate was 54.5%. Five patients (45.4%) developed hemodynamic compromise in an average of 5 days after transplantation, presenting with sudden onset of fatal arrhythmia (n = 4; 80%) and immediate heart failure (n = 1; 20%). All 5 patients underwent immediate resuscitation and extracorporeal membrane oxygenation (ECMO) support, and 3 patients died (60%); in contrast, the other 6 patients suffered from progressively worsening cardiac function during long-term follow-up. Three patients (50%) died in this group.

Conclusions

Clinical presentation of AMR varies. Long-term postoperative follow-up in the form of endomyocardial biopsy is recommended with immunohistochemistry C4d staining, with the anticipation of the possibility of future recurrence.  相似文献   

20.
《Transplantation proceedings》2023,55(4):1089-1091
BackgroundWe report a case of suspected hyperacute rejection during living kidney transplantation.Case reportA 61-year-old man underwent kidney transplantation in November 2019. Before the transplantation, immunologic tests revealed the presence of anti-HLA antibodies but not donor-specific HLA antibodies. The patient was intravenously administered 500 mg of methylprednisolone (MP) and basiliximab before perioperative blood flow reperfusion. After blood flow restoration, the transplanted kidney turned bright red and then blue. Hyperacute rejection was suspected. After the intravenous administration of 500 mg of MP and 30 g of intravenous immunoglobulin, the transplanted kidney gradually changed from blue to bright red. The initial postoperative urine output was good. On the 22nd day after the renal transplantation, the patient was discharged with a serum creatinine level of 2.38 mg/dL, and the function of the transplanted kidney gradually improved.ConclusionsIn this study, non-HLA antibodies may have been a cause of the hyperacute rejection, which was managed with additional perioperative therapies.  相似文献   

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