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1.
Because of the current organ shortage, ABO‐incompatible (ABOi) transplantations have been increasingly performed in recent years. The results seem comparable to those of compatible transplantations, but there have also been reports of increased side effects possibly because of the desensitization therapy. To address an increase in severe infectious complications, we compared the outcomes of 48 ABOi transplant recipients to outcomes of 96 matched ABO‐compatible (ABOc) controls transplanted at Heidelberg University Hospital from August 2005 to April 2018. Over a follow‐up period of 8 years, ABOi transplant recipients had comparable graft and patient survival as well as graft function compared with ABOc patients. T‐cell‐mediated and antibody‐mediated rejections were not different between groups. In ABOi transplant recipients, urosepsis (22.9% vs. 8.5%; P = 0.019) and pneumonia with opportunistic pathogens (8.3% vs. 1.0%, P = 0.025) appeared more frequently. As a consequence, a significantly higher number of deaths from infection have been observed after ABOi transplantations (6.3% vs. 0%, P = 0.010). High‐titer recipients (isoagglutinin titer of ≥1:256) showed a higher incidence of BK virus replication and postoperative bleeding complications. ABO‐incompatible transplantations can be performed with results that are not different from results after ABOc transplantations. However, an increased rate of serious infectious complications must be taken into account.  相似文献   

2.
The efficacy and safety of everolimus (EVR) in simultaneous pancreas and kidney transplantation (SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low‐dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric‐coated mycophenolate sodium (EC‐MPS); two patients who received sirolimus were excluded from the analysis. With a median follow‐up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC‐MPS patients, respectively. One EC‐MPS patient lost her kidney graft from proteinuric kidney disease. Another EC‐MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short‐term outcome to EC‐MPS when combined with low‐dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow‐up is required to further assess this combination.  相似文献   

3.
Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune‐mediated injury and loss of function. Accommodation was discovered and has been explored most thoroughly in ABO‐incompatible kidney transplantation. In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens. Whether accommodation is owed to changes in anti‐blood group antibodies, changes in antigen or a change in the response of the transplant to antibody binding are critically reviewed and a new working model that allows for the kinetics of development of accommodation is put forth. Regardless of how accommodation develops, observations on the fate of ABO‐incompatible transplants offer lessons applicable more broadly in transplantation and in other fields.  相似文献   

4.
The required intensity of monitoring for antibody‐mediated rejection (AMR) after of ABO‐incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single‐center cohort of 115 ABO‐incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk‐stratified patients into high‐ and low‐risk groups for the development of late AMR; 26% of patients had at least one AMR episode; 49% of AMR episodes occurred within 30‐days after transplant and were considered early AMR. Patients with an early AMR episode had a 5.5‐fold greater incidence of developing late AMR [IRR = 5.5, (95% CI: 1.5–19.3), P = 0.01]. ABOi/HLAi recipients trended toward increased late AMR risk [IRR = 1.9, (95% CI: 0.5–6.6), P = 0.3]. High‐risk recipients (those with an early AMR or those who were ABOi/HLAi) had a sixfold increased incidence of late AMR [IRR = 6.3, (95% CI: 1.6–24.6), P = 0.008] versus low‐risk recipients. The overall incidence of late AMR was 20.8% vs. 1.5% in low‐risk recipients. Changes in anti‐A/B titer did not correlate with late AMR (IRR = 0.9 per log titer increase, P = 0.7). This risk‐stratification scheme uses information available within 30 days of ABOi transplantation to determine risk for late AMR and can help direct longitudinal follow‐up for individual patients.  相似文献   

5.
In this 12‐month, multicenter, randomized, open‐label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low‐dose tacrolimus (EVR+LTac) or mycophenolate mofetil plus standard‐dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti‐thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy‐proven acute rejection [tBPAR]/graft loss/death/loss to follow‐up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% [?3.0, 11.4]). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow‐up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 [22.0] vs. 63.1 [19.5] mL/min/1.73 m2) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.  相似文献   

6.
A key objective in the use of immunosuppression after kidney transplantation is to attain the optimal balance between efficacy and safety. In a phase 3b, multicenter, randomized, open‐label, noninferiority study, the incidences of clinical events, renal dysfunction, and adverse events (AEs) were analyzed at 12 months in 309 de novo renal transplant recipients receiving everolimus (EVR), low‐dose tacrolimus (LTac), and prednisone. Cox proportional hazard regression modeling was used to estimate the probability of clinical events at specified combinations of time‐normalized EVR and Tac trough concentrations. At 12 months, the highest incidence of treated biopsy‐proven acute rejection (tBPAR) and graft loss occurred most often in patients with EVR trough concentration <3 ng/mL (64.7% and 10.5%, respectively). At 1 month and 12 months, increasing EVR levels were associated with fewer tBPAR events (both p < 0.0001). Low estimated glomerular filtration rate (eGFR) and decreased eGFR occurred more often in patients with lower EVR and higher Tac levels. AEs were most often observed in patients with EVR levels <3 ng/mL. This study supports maintaining an EVR trough concentration of 3–8 ng/mL, when combined with LTac, to achieve balanced efficacy and safety in renal transplant recipients. Trial registration: NCT01025817.  相似文献   

7.
ABO‐incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus‐based immunosuppressive regimen to contemporaneous ABO‐compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7–14 days pretransplant). Antibody depletion was scheduled according to baseline anti‐ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18–32). Eight rejection episodes (two antibody‐mediated and six cellular) in ABOi recipients were successfully treated with biopsy‐proven resolution. Latest median eGFR is 50 mL/min × 1.73 m2 (IQR 40–64) for ABOi patients and 54 mL/min × 1.73 m2 (IQR 44–66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end‐stage kidney disease patients.  相似文献   

8.
A steroid‐free protocol for ABO‐compatible renal transplantation has been used at our center since 1983. To minimize the adverse effects of steroids, we also developed a steroid sparing protocol for ABO‐incompatible renal transplantation in 2008. The present study is a report of our results. A retrospective review of the first 50 ABO‐incompatible renal transplantations performed at a single university center. If no immunological events occurred in the post‐transplant period, prednisolone tapering was initiated approximately 3 months after transplantation. Forty‐three patients completed prednisolone tapering after 289 ± 58 days. Three patients died during follow‐up, and four patients lost graft function. None of these adverse events were rejection related. Eleven patients experienced rejections; seven were on prednisolone and four were after weaning from prednisolone. All patients responded well to antirejection treatment. Overall, 1‐year rejection rate was 19%. One‐ and 3‐year graft survival was 94% and 91%, respectively. One‐year post‐transplant median serum creatinine was 123 μmol/L. We found acceptable rejection rates, graft survival, and creatinine levels in patients undergoing ABO‐incompatible renal transplantations with a steroid sparing protocol. However, a longer follow‐up of a lager cohort is needed before firm conclusions can be made.  相似文献   

9.
ABO‐blood group incompatible infant heart transplantation has had excellent short‐term outcomes. Uncertainties about long‐term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO‐incompatible recipients. ABO‐incompatible (n = 35) and ABO‐compatible (n = 45) infant heart transplantation recipients (≤14 months old, 1996–2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor‐specific antibodies against blood group antigens, in only two ABO‐incompatible patients were these antibodies implicated in antibody‐mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow‐up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO‐blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO‐compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor‐specific isohemagglutinins and the implications for graft accommodation are warranted.  相似文献   

10.
Screening for polyoma BK virus (BK) using nucleic testing (NAT) is recommended for kidney and kidney‐pancreas transplant recipients, but the performance characteristics of quantitative BK NAT at different thresholds of plasma BK viral loads are unclear. We aim to evaluate the diagnostic accuracy of quantitative BK NAT as an add‐on test to qualitative polyoma NAT for the diagnosis of BK virus‐associated nephropathy (BKVAN) in kidney and kidney transplant recipients. We calculated the test sensitivity, specificity, and predictive values at the different thresholds of plasma BK viral load for BKVAN. At the recommended threshold of >1 × 103 serum BK copies/mL serum for test positivity, the sensitivity for BKVAN was 92.9% (95% confidence intervals [CI]: 66.1–99.8) and specificity 79.1% (95%: CI 67.4–88.1), with corresponding positive and negative predictive values of 42.0% (95% CI: 24.8–57.7%) and 98.6% (95% CI: 98.3–99.9%), respectively. The overall area under curve for the quantitative BK NAT was 0.92 (95% CI: 0.85–0.97). Quantitative BK NAT displays properties of high sensitivity and specificity that are fit for purpose as an add‐on test to qualitative polyomavirus NAT for kidney and kidney‐pancreas transplant recipients at risk of BKVAN.  相似文献   

11.
The infrequent use of ABO‐incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2‐incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3‐year posttransplant costs. The marginal costs of ABOi and A2i versus ABO‐compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death‐censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc ‐ year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long‐term dialysis and its associated morbidity and cost.  相似文献   

12.
ABO‐incompatible living kidney transplantation (ABO‐ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO‐ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO‐ILKT compared with those from ABO‐compatible living kidney transplantation (ABO‐CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032—including 247 ABO‐ILKT and 785 ABO‐CLKT cases—were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO‐compatibility. In the past decade, ABO‐ILKT and ABO‐CLKT recipients yielded almost equivalent outcomes with respect to the 9‐year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59–3.22, p = 0.455). The graft survival rate for ABO‐ILKT conducted between 2005 and 2013 was better than that for ABO‐ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13–0.72, p = 0.007). ABO‐ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO‐incompatibility. Currently, ABO‐ILKT is an acceptable treatment for patients with end‐stage renal disease.  相似文献   

13.
BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.  相似文献   

14.
BackgroundOne of the major barriers for long-term renal graft survival is considered to be calcineurin inhibitor nephrotoxicity, contributing to chronic graft dysfunction. Thus, recent immunosuppressive strategies are focused on regimens that can reduce or avoid exposure to calcineurin inhibitors. Herein, we carried out a small-scale pilot study to assess whether everolimus (EVR) with reduced-dose tacrolimus (Tac) is an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant compared with mycophenolate mofetil (MMF) with standard-dose Tac.MethodsThis retrospective single-center cohort study included patients who underwent ABO-incompatible kidney transplant at our institution between January 2016 and December 2019. Those whose immunosuppressive regimen was changed by reasons other than rejection during the 1-year follow-up period were excluded.ResultsA total of 24 patients were enrolled in this study: 10 patients who received an EVR with reduced-dose Tac regimen and 14 patients who received an MMF with standard-dose Tac regimen. Tac trough levels in the EVR group were significantly lower than those in the MMF group (P < .001). No patients died or lost their grafts during the follow-up period. There were no significant differences in renal function, proteinuria, and prevalence of hyperlipidemia between the 2 groups at 1 year after transplant. There were no significant differences in the incidence of rejection (acute cellular rejection, steroid-resistant acute cellular rejection, acute antibody-mediated rejection) and infection (cytomegalovirus viremia, cytomegalovirus disease, BK viremia, BK virus nephropathy) between the 2 groups.ConclusionsComparable with MMF with standard-dose Tac, EVR with reduced-dose Tac might be an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant.  相似文献   

15.
Everolimus allows calcineurin‐inhibitor reduction without loss of efficacy and may improve renal‐transplant outcomes. In a 24‐month, open‐label study, 833 de novo renal‐transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3–8 and 6–12 ng/mL, respectively) with reduced‐exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard‐exposure CsA. Patients received basiliximab ± corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy‐proven acute rejection, graft loss, death or loss to follow‐up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last‐observation‐carried‐forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m2 in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: ?1.7, 6.4 and ?5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard‐exposure CsA plus MPA.  相似文献   

16.
目的观察稳定期肾移植受者由普通剂型他克莫司(Tac)转换为缓释剂型Tac后对移植肾功能的影响。方法回顾性分析山西省第二人民医院2011年12月至2019年6月由普通剂型Tac转换为缓释剂型Tac的83例稳定期肾移植受者,随访12~36个月,同时匹配83例继续服用普通剂型Tac的稳定期肾移植受者作为对照组。观察稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac后肾功能、谷值浓度个体内变异度(IPV)及依从性的变化、排斥反应的发生率及移植肾和移植受者的存活率。结果普通剂型Tac转换为缓释剂型Tac时间为移植后(42.76±30.50)个月,转换后24个月血清肌酐(SCr)明显低于转换前(P=0.013),估算肾小球滤过率(eGFR)明显高于转换前(P=0.005)。试验组较对照组在转换后36个月SCr明显降低(P=0.017),eGFR明显增高(P=0.038)。试验组转换前免疫抑制剂治疗障碍量表(ITBS)得分为(20.23±2.89)分,转换后为(17.63±3.08)分(P=0.000);Tac每日剂量转换前是(2.09±0.84)mg,转换后为(2.10±0.83)mg;Tac谷值浓度转换前为(7.22±2.84)ng/mL,转换后显著降低,人/肾均健康存活。结论稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac肾功能保持稳定且较普通剂型Tac相对更好,依从性明显改善,谷值浓度个体内变异度明显降低,长期服用的临床疗效和安全性良好。  相似文献   

17.
ABO‐incompatible kidney transplantation (ABO‐ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO‐compatible kidney transplantation (ABO‐CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO‐ILKTs and ABO‐CLKTs at 2 years post‐transplantation. We included 65 ABO‐ILKTs and 94 ABO‐CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO‐CLKT and ABO‐ILKT. The hospitalization costs for ABO‐CLKT and ABO‐ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2‐year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO‐CLKT and ABO‐ILKT, respectively, indicating that the medical costs of ABO‐ILKT recipients were non‐significantly higher than those of ABO‐CLKT recipients at 2 years post‐transplantation (P = 0.0866). ABO‐ILKT and ABO‐CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post‐transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO‐ILKT group than in the ABO‐CLKT group. ABO‐ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO‐CLKT not only in terms of outcomes but also in terms of medical cost.  相似文献   

18.
Forty‐eight hour kidney transplantation admissions are a feasible option in selected recipients of live‐donor allografts through the use of standardized post‐operative protocols, multidisciplinary team patient care, and intensive follow‐up at outpatient centers. Age, gender, and pre‐transplant dialysis status did not impact the ability to achieve 48‐hour admissions. We did not identify any other pre‐operative risk factors that contributed to increased length of stay. Although ABO and highly sensitized recipients had longer lengths of stay, the subgroup was too small to achieve statistical significance. We did not encounter any readmissions within the first seven post‐operative days. Further improvements in clinical management will enhance the potential to shorten the length of hospital stay for all kidney transplant recipients.  相似文献   

19.
20.
Redfield RR, Parsons RF, Rodriguez E, Mustafa M, Cassuto J, Vivek K, Noorchashm H, Naji A, Levine MH, Abt PL. Underutilization of A2 ABO incompatible kidney transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01543.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: ABO compatibility creates a disadvantage for O and B renal allograft candidates. A2 ABO incompatible transplant may decrease waiting times and generate equivalent graft survival to an ABO compatible transplant. Methods: Death‐censored graft survival was compared between A recipients and O, B, and AB recipients of an A2 allograft with multivariate Cox regression models utilizing data from the United Network of Organ Sharing (UNOS) between 1997 and 2007. Results: Eighty‐five percent of A2 kidneys were transplanted into ABO compatible recipients vs. 15% into ABO incompatible recipients. Rates of A2 incompatible kidney transplants did not increase over the study period (14.8% to 14.6%). Mean wait time for A2→O kidneys was 337 vs. 684 d for O→O and for A2→B kidneys, 542 vs. 734 d for B→B. Adjusted relative risk of graft loss at five‐yr was similar between O, B, and AB recipients compared to A recipients of an A2 allograft, corresponding to a five‐yr graft survival of 84%, 86.2%, 86.1%, and 86.1%, respectively. Conclusion: A2 incompatible kidney transplantation is underutilized. Graft outcomes are similar among A2 compatible and incompatible recipients. Shorter waiting time and improved access might be achieved if A2 kidneys are considered in all blood groups.  相似文献   

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