肾移植术后供者特异性抗体对移植肾近期效果的影响

目的 评价肾移植术后供者特异性抗体(Ds-Ab)对移植肾近期效果的影响。方法 对2001年1月至2002年7月间进行尸肾移植的92例受者，使用酶联免疫吸附(ELISA)法，检测受者血清中HLA抗体水平，随访1年。结果 16例(17．4％)受者术后出现供者特异性抗体。抗体阳性组急性排斥发生率(56．3％)高于抗体阴性组(11．9％)，P=0．000；移植肾功能延迟恢复的发生率(12．5％)与抗体阴性组(9．2％)比较，差异无显著性，P=0．102；供者特异性抗体阳性组受者发生急性排斥后，移植肾肌酐水平高于抗体阴性组或无急性排斥组。结论 供者特异性抗体与肾移植术后急性排斥有关，可能影响近期移植肾功能。     

Impaired kidney transplant survival in patients with antibodies to hepatitis C virus.

BACKGROUND: With a few exceptions, most published studies do not show an influence of antibodies to the hepatitis C virus (HCV) on the success of a kidney transplant. METHODS: We studied all our renal transplant recipients who had received kidneys from cadaver donors (n = 335) and had been treated with quadruple immunosuppression (steroids, azathioprine, and antilymphocyte antibodies, followed by cyclosporin). We had information on the status of the hepatitis C antibodies before and/or after the transplant in 320 cases (95.5%; in 300, pre-transplant). Patients with HCV antibodies before and/or after the transplant were considered to be HCV positive (HCV+). RESULTS: The HCV+ patients had more time in dialysis and a greater number of transfusions, hyperimmunized cases, and re-transplants. The evolution in the first post-transplant year was similar in both groups, but afterwards, the HCV+ patients had proteinuria more often as well as worse kidney function. The survival rate of the graft was significantly less in the HCV+ cases: 90.6, 68.3 and 51.0% at respectively 1, 5 and 10 years, compared with 91.5, 84.7 and 66.5% in HCV-patients (P<0.01). The patient survival rate was: 96.4, 87.0, and 71.9% in the HCV+ patients at 1, 5, and 10 years, compared with 98.2, 96.0 and 90.0% in the HCV- cases respectively (P<0.01). The differences remained the same in stratified studies according to time spent in dialysis or pre/post-transplant evolution of HCV antibodies, even when immunologically high-risk patients were excluded. In multivariant analysis, the presence of HCV antibodies acted as a independent prognostic factor for the survival of the kidney and the patient: 3.0 (1.8-5.0) and 3.1 (1.2-7.8) odds-ratio (95% of the confidence interval), respectively. The main cause of death among HCV+ patients was cardiovascular; there was no apparent increase in mortality rate due to infections or chronic liver disease. The loss of organs was mainly due to chronic nephropathy or death with a functioning kidney. CONCLUSION: The presence of hepatitis C antibodies, before or after transplantation, is associated with a worse long-term survival rate for both the patient and the transplanted kidney in our patients treated with quadruple therapy.     

Association of donor-specific microchimerism with graft dysfunction in kidney transplant patients

The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11 (29%) SRF patients (Odds Ratio 7.36, 95% CI 1.7-35.2; p<0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5×10(-5) vs. 2.4×10(-5); p<0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients.     

Comparative analysis of two methods to detect donor-specific anti-HLA antibodies after kidney transplant

Preformed anti-human leukocyte antigen (HLA) antibodies may be present in the blood of kidney transplant candidates. The production of these antibodies may occur in the post-transplant period, with the possible development of donor-specific antibodies (DSA). Luminex-based tests, such as the single antigen (SA) assay and the Luminex crossmatch (Xm-DSA) assay are the most commonly used tools to detect anti-HLA antibodies, due to their high sensitivity and specificity. This cross-sectional study aimed to compare the findings of two methods for the detection of DSAs after kidney transplant: SA and Xm-DSA. A total of 122 patients who underwent deceased donor kidney transplant at Hospital de Clínicas de Porto Alegre were included. The SA assay detected anti-class I HLA DSAs in 17 patients (13.9%) and anti-class II HLA DSAs in 22 patients (19.6%), whereas the Xm-DSA detected DSAs in 18 patients (14.8%) both against class I and class II antigens. There was agreement between the two methods for class I (kappa = 0.66, p = 0.001) and class II (kappa = 0.54, p = 0.025) antigens. The incidence of DSAs as obtained by the SA assay was 15.57%, and the most prevalent DSAs were those against HLA-DR antigens. Patient survival at 3 years was 92%. The two techniques assessed in this study provide important information on the presence of DSAs and may help in the post-transplant patient monitoring and in immunosuppressive strategy.     

Impact of acute kidney injury on renal allograft survival

Background: Acute kidney injury (AKI) is one of the major determinants of graft survival in kidney transplantation (KTx). Renal Transplant recipients are more vulnerable to develop AKI than general population. AKI in the transplant recipient differs from community acquired, in terms of risk factors, etiology and outcome. Our aim was to study the incidence, risk factors, etiology, outcome and the impact of AKI on graft survival.

Methods: A retrospective analysis of 219 renal transplant recipients (both live and deceased donor) was done.

Results: AKI was observed in 112 (51.14%) recipients, with mean age of 41.5?±?11.2 years during follow-up of 43.2?±?12.5 months. Etiologies of AKI were infection (47.32%), rejection (26.78%), calcineurin inhibitor (CNI) toxicity (13.39%), and recurrence of native kidney disease (NKD) (4.46%). New Onset Diabetes After Transplant (NODAT) and deceased donor transplant were the significant risk factors for AKI. During follow-up 70.53% (p?=?.004) of AKI recipients progressed to chronic kidney disease (CKD) in contrast to only 11.21% (p?=?.342) of non AKI recipients. Risk factors for CKD were AKI within first year of transplant (HR: 7.32, 95%CI: 4.37–15.32, p?=?.007), multiple episodes of AKI (HR: 6.92, 95%CI: 3.92–9.63, p?=?.008), infection (HR: 3.62, 95%CI: 2.8–5.75, p?=?.03) and rejection (HR: 9.92 95%CI: 5.56–12.36, p?=?.001).

Conclusion: Renal transplant recipients have high risk for AKI and it hampers long-term graft survival.     

HLA-DR matched transfusions: development of donor-specific T- and B-cell antibodies and renal allograft outcome

BACKGROUND: Pretransplant blood transfusions are reported to decrease acute rejection rate and increase graft survival after renal transplantation. This has been attributed to matching for HLA-DR with the transfusion donor, which also results in a lower rate of sensitization. METHODS: The development of donor-specific T- and B-cell antibodies was measured by National Institutes of Health and two-color fluorescence assays after one transfusion in 247 naive patients. Auto-cross-matches were performed to exclude autoantibodies. Patients were grouped according to DR-matching (n=107) or nonmatching (n=140) with the transfusion donor. In 103 renal allograft recipients, acute rejection rate and graft survival were analyzed by Cox regression. RESULTS: T-cell antibodies developed in 6.5% of the patients. There was no difference between the DR-matched and nonmatched group. No auto-antibodies against T-cells developed, whereas one quarter of the sera had a positive B-cell auto-cross-match. There was no difference with regard to B-cell antibodies (auto-antibody-positive sera excluded) between the DR-matched (15.8%) and nonmatched (18.6%) group. Sharing of HLA A and/or B antigens did not result in a lower frequency of donor-directed T- or B-cell antibodies. None of the risk factors, including DR sharing with transfusion donor, contributed significantly towards graft survival (odds ratio for DR sharing: 1.02; 95% confidence interval: 0.45-2.32; P=0.97). DR sharing was no risk factor towards acute rejection either, in contrast to DR mismatch with kidney donor (odds ratio: 2.9), and use of cyclosporine versus tacrolimus (odds ratio: 4.4). CONCLUSIONS: Development of donor-directed T-cell antibodies after one transfusion of leukocyte-poor blood is low and irrespective of HLA-DR match with transfusion donor. B-cell antibodies develop more frequently and independent of HLA-DR match. In 26% of the sera, B-cell auto-antibodies are detected. Rejection rate and graft survival are not significantly different between HLA-DR-matched and nonmatched transfusions.     

Detection of donor-specific anti-HLA antibodies with flow cytometry in eluates and sera from renal transplant recipients with chronic allograft nephropathy

BACKGROUND: Chronic allograft nephropathy (CAN), which remains the main cause of graft loss after kidney transplantation, is still poorly understood. Because anti-HLA antibodies may be involved in the pathogenesis of CAN, this study was performed to look for donor-specific antibodies (DSA) fixed onto renal transplants with CAN. METHODS: DSA were identified after elution with flow cytometric assay and/or flow cytometric crossmatches in 20 transplants removed after irreversible graft failure caused by CAN and in control samples from 2 transplants with relapsing glomerulopathy, 2 transplants lost after vascular thrombosis, and 4 normal kidneys. The results were compared with those obtained in the serum samples 1 year after grafting, at the time of transplantectomy, and within 2 months after transplantectomy. RESULTS: IgG anti-class I, anti-class II, or both DSA were identified in 70.6% of eluates versus 73.6% of posttransplantectomy serum samples (NS), 42.1% of 1-year postgrafting serum samples (P<0.05), and 31.6% of serum samples at the time of transplantectomy (P<0.05). Our data show a good correlation between the target of anti-HLA antibodies found in both eluates and posttransplantectomy serum samples, but the precise specificity of anti-HLA antibodies is more often assigned in posttransplantectomy serum samples than in eluates. This problem needs further evaluation. CONCLUSION: This study shows that testing for anti-HLA DSA in eluates from removed kidney transplants using flow cytometry can be achieved and is highly efficient. It already suggests that both anti-class I and anti-class II HLA antibodies can be involved in CAN. Further studies are now needed to evaluate the possibility of identifying such antibodies in the eluates of transplant biopsy specimens from recipients experiencing CAN.     

De novo donor-specific HLA antibodies reduce graft survival rates and increase the risk of kidney transplant rejection: A single-center retrospective study

BackgroundWe investigated the impact of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection in kidney transplant recipients.MethodsThe sample for this retrospective cohort study comprised 121 recipients of kidney transplants with negative complement-dependent cytotoxicity crossmatches to their deceased donors. Recipients were divided into two groups: dnDSAs+ (n = 31) and dnDSAs- (n = 90). We evaluated rejection and long-term graft survival rates in the recipients along with pathologic changes in the transplanted kidneys.ResultsDnDSAs were identified in 31/121 patients (25.6%). The graft survival rate in the dnDSAs+ group was 87.1% (27/31) and that of the dnDSAs- group was 97.8% (88/90). The dnDSAs+ group had lower graft survival rates than patients without dnDSAs (p = 0.007). There was no difference in the graft survival rates between patients with high DSA mean fluorescence intensity (≥4000) and those with low intensity (<4000) (p = 0.669). There was also no difference in the graft survival rates of patients with HLA class I, II, and I + II dnDSAs (p = 0.571). The presence of dnDSA in serum was associated with a higher incidence of antibody- and T-cell–mediated rejection (p < 0.0001). Banff scores for arterial fibrointimal and arteriolar hyalin, thickening as well as C4d deposition differed for the dnDSAs+ and dnDSAs- groups (p < 0.05).ConclusionDnDSAs were found to be associated with decreased long-term graft survival rates and increased rejection rates, often accompanied by C4d deposition.     

Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft

We have recently developed a sensitive limiting dilution (LD) culture system to measure human alloreactive cytotoxic T lymphocyte precursors (CTL-p) in a given lymphoid cell population. We have now used this system to determine frequencies of donor HLA antigen-inducible CTL-p in the peripheral blood of human allograft recipients at various stages after transplantation. All patients (1 pancreas recipient and 9 kidney recipients) were on continuous cyclosporine treatment throughout the study. We report that, in patients with a well-functioning kidney graft (6/9), the number of donor-reactive CTL-p among peripheral blood lymphocytes decreased within 3-8 months after transplantation--in some cases (2/6) more than 10-fold. In contrast, frequencies of CTL-p with specificity for third-part HLA antigens remained largely unaltered in these patients. Furthermore, no decrease of donor-reactive CTL-p frequencies was seen in 3 of 4 patients showing clinical symptoms of graft rejection. These results indicate that functional clonal deletion of antigraft-reactive CTL-p may contribute to the state of graft tolerance in certain patients with a well-functioning kidney allograft.     

Cytomegalovirus prophylaxis with ganciclovir in kidney transplant recipients receiving induction antilymphocyte antibodies

BACKGROUND: Cytomegalovirus (CMV) is one of the serious viral infections after organ transplantation, especially in patients receiving anti-lymphocyte antibodies. Prevention of the infection using antiviral chemotherapy (ganciclovir) has gained interest in the transplant community due to the availability of quantitative methods for viral detection and monitoring. METHODS: Forty-six CMV seropositive kidney transplant recipients were assigned to receive induction immunosuppression with anti-thymocyte globulin (ATG, Fresenius). Prophylactic intravenous ganciclovir was administered for 2 weeks at a dose of 5 mg/kg/d (adjusted to kidney function) starting from the day of surgery. Patients were monitored regularly for CMV infection or disease over 1 year posttransplant. The time to CMV manifestation, the number of antigenemia assay-positive cells, the clinical severity of infection, the incidence of acute rejection, the graft function, and the duration of hospital stay were evaluated. This group was compared to a historical matched control cohort (n = 37) transplanted earlier who did not receive prophylactic ganciclovir. RESULT: The incidence of CMV disease was significantly less among the prophylaxis than the control group (6/46 patients [13%] vs 16/37 patients [43.2%], P = <.004). The time to develop CMV manifestations was much longer in the prophylaxis group than in the control group (median 92 vs 32 days, P 相似文献   

Impact of renal graft nephrectomy on second kidney transplant survival

Purpose

To determine the impact of non-functional renal graft nephrectomy on second kidney transplantation survival.

Methods

We performed a retrospective study on patients managed in our department from April 1989 to April 2011. We compared the number of acute graft rejections and graft survival between patients undergoing second transplantation with (Group I) or without (Group II) prior graft nephrectomy.

Results

A total of ninety-one patients received a second renal graft: 43 underwent graft nephrectomy and 48 kept their non-functional renal graft. There were 5 episodes of acute graft rejection in Group I and 12 in Group II (p = 0.3). Six (13.9 %) grafts failed in Group I and eight (16.6 %) in Group II. Five and 10 years actuarial graft survival in Group I were, respectively, 91 and 85 %, while in Group II were 82.7 % and 69 % (p = 0.2). PRA level and number of acute rejection episodes did not have a statistically significant influence on graft survival, whether the patient had a nephrectomy or not (p = 0.2).

Conclusion

Nephrectomy of a failed allograft did not significantly improve the survival of a subsequent graft. Graft nephrectomy should be indicated in case of graft-related pain or a chronic inflammation syndrome.     

Failure to prolong pancreatic islet allograft survival in rats with donor-specific blood transfusions and immunosuppression

The effects on pancreatic islet allograft survival of donor-specific blood transfusions (DST) in combination with pre- and posttransplant immunosuppression were studied. A total of 12 groups of rats (n=105) with chemically induced diabetes underwent islet allotransplantation. Multiple DST or third-party blood transfusions (TPT) were given prior to transplantation. Pretransplant immunosuppression consisted of azathioprine and prednisolone, and low-dose cyclosporin A was used for posttransplant immunosuppression. TPT, as well as separate or combined pre- and posttransplant immunosuppression without blood transfusions, did not prolong islet allograft survival. DST resulted in either primary nonfunction of the islet allografts or a markedly decreased islet allograft survival. These findings contrast with the beneficial effect of DST on whole-organ allograft survival in rats previously described by others.