Detection of antibodies to HLA-DP in renal transplant recipients using single antigen beads

With the development of single DP-antigen beads, antibodies to DP could clearly be segregated from other HLA antibodies. We studied 323 sera of patients from four different centers with functioning or rejected kidney grafts. DP antibodies were found in 5.1% of 138 patients with functioning grafts, and 19.5 % of 185 patients with rejected grafts (P<0.001)). 42.9% and 63.9% of the DP antibody positive patients had DR/DQ antibodies among the functioning and rejected group. Among patients who did not have Class I and DR/DQ antibodies, 13% of those who rejected a graft had DP antibodies, compared to 3.5% of patients with functioning grafts (P<0.05). DP 0301 had the highest specificity frequency in the rejected group. In conclusion, HLA-DP antibodies were detected at a higher frequency in patients who have rejected their grafts than those with functioning grafts. For regrafts, DP tissue typing is recommended to avoid presensitized DP alleles.     

Four-year Follow-up of a Prospective Trial of HLA and MICA Antibodies on Kidney Graft Survival

In 2002, 1329 patients with functioning transplants were prospectively tested for HLA antibodies in the 13th International Histocompatibility Workshop. Four years after testing, deceased donor graft survival among 806 patients not having antibodies in 2002 was 81% compared to 58% for 158 patients with HLA antibodies (p < 0.0001) and 72% for 69 patients with MICA antibodies (p = 0.02). Hazard ratio (HR) using death-censored graft survival from multivariate analysis of HLA antibodies was 3.3 (p < 0.00001) and 2.04 for MICA (p = 0.01). In the 14th Workshop, at 1 year follow-up, survival for 1319 patients receiving deceased donor grafts and no HLA antibodies was 96% compared to 94% for 344 patients with HLA antibodies (p = 0.0004) and 83% survival for 33 patients with MICA (p = 0.0005). HR from multivariate analysis: HLA antibodies was 3.6 (p < 0.00001) and 6.1 for MICA (p = 0.006). Twelve patients with donor specific antibodies tested by single antigen beads had a 1 year survival of 64% (p = 0.008), and 27 patients with non-donor specific 'strong' antibodies had a 66% survival (p = 0.0003) compared to 92% survival in those with no antibodies. In conclusion, these two prospective trials, after 1 and 4 years, provided strong evidence that HLA and MICA antibodies are associated with graft failure.     

Soluble HLA-G Expression and Renal Graft Acceptance

HLA-G is a potentially interesting molecule associated with immunosuppressive function. We survey here the presence of soluble HLA-G (sHLA-G) in serial serum samples of renal transplants. A total of 330 sera of from 65 patients were tested for sHLA-G with ELISA. IgG/IgM antibodies to HLA, and MICA antibodies were also previously tested. After serial analysis of the 65 patients' 330 sera, 50% of 26 patients in functioning group had consistent sHLA-G expression or became positive, in comparison to 20.5% among 39 patients who rejected their transplants (p=0.013). Thus sHLA-G was associated with functioning transplants. Eighty percent (77 of 96) of the HLA IgG positive sera had no sHLA-G expression, while 81.4% (83 of 102) of the HLA-G(+) sera had no HLA IgG (p=0.005), which showed a negative association between sHLA-G and the presence of HLA IgG antibodies (which was previously been shown to be associated with failure). In this preliminary survey, sHLA-G was found in the serum of about 30% of renal transplant patients. sHLA-G had a negative association with allograft failure from chronic rejection, and a negative relationship with the production of HLA IgG antibodies. The significance of sHLA-G in renal transplants remains to be determined.     

Clinical relevance of pre and post-transplant immune markers in kidney allograft recipients: anti-HLA and MICA antibodies and serum levels of sCD30 and sMICA

BackgroundThis retrospective study aims to determine the prognostic values of HLA and MICA antibodies, serum levels of sCD30 and soluble form of MHC class I related chain A (sMICA) in kidney allograft recipients.MethodsSera samples of 40 living unrelated donor kidney recipients were tested by ELISA and Flow beads techniques for the presence of anti HLA and MICA antibodies and the contents of sCD30 and sMICA. HLA and MICA antibody specification was performed by LABScreen single antigen beads to determine whether the antibodies were directed against donor mismatches.ResultsWithin first year post operatively 9 of 40 patients (22.5%) showed acute rejection episodes (ARE) that four of them lost their grafts compared to 31 functioning transplants (P = 0.001). The presence of HLA antibodies before and after transplantation was significantly associated with ARE (P = 0.01 and P = 0.02 respectively). Sensitization to HLA class II antigens pre-transplant was strongly associated with higher incidence of ARE (P = 0.004). A significant correlation was found between ARE and appearance of non-donor specific antibodies (P = 0.02). HLA antibody positive patients either before or after transplantation showed lower graft survival rates than those without antibodies during three years follow-up (P = 0.04 and P = 0.02). Anti-MICA antibodies were observed in 8/40(20%) and 5/40(12.5%) of patients pre and post-transplant respectively. Coexistence of HLA and MICA antibodies was shown in 2 of 4 cases with graft loss. A significant increased level of sCD30 at day 14 (P = 0.001) and insignificant decreased levels of sMICA pre and post operatively were detected in rejecting transplants compared to functioning graft group.ConclusionOur findings support the view that monitoring of HLA and MICA antibodies as well as sCD30 levels early after transplant has predictive value for early and late allograft dysfunctions and the presence of these factors are detrimental to graft function and survival.     

Predicting Kidney Graft Failure by HLA Antibodies: a Prospective Trial

HLA antibodies have been shown to be associated with late graft loss of organ transplants in prior studies. Recently they were even shown to appear years BEFORE rejection. (1) An international cooperative study of 4763 patients from 36 centers was undertaken to determine the frequency of HLA antibodies in patients with functional transplants. The overall frequency of HLA antibodies among kidney transplant recipients was 20.9%; 19.3% in the liver, 22.8% in the heart, and 14.2% in the lung. Patients treated with CsA-MMF had significantly lower antibodies (9.8%) than those treated with CsA-Aza (18.1%) (0.00008). (2) Second, a prospective trial was performed in 23 kidney transplant centers to determine whether HLA antibodies could predict failures within 1 year. Among the 2278 patients followed up, 91 grafts failed and 34 patients died. Of 500 patients who had HLA antibodies, 6.6% failed compared with 3.3% among 1778 patients without antibodies (p = 0.0007). Among 244 patients who made de novo antibodies, 8.6% failed compared with 3.0% failures among 1421 patients who did not make antibodies (p = 0.00003). Death occurred in 1.5% of patients and was not associated with antibodies. Thus, after 1 year in this prospective trial, patients with HLA antibodies had graft failure at a significantly higher rate than those without antibodies.     

Human leukocyte antigen and major histocompatibility complex class I-related chain a antibodies after kidney transplantation in Turkish renal transplant recipients

Background

This study was designed to determine whether human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related A (MICA) antibody (Ab) production during the first 6 months posttransplantation correlated with long-term graft survival and rejection rate. The study group included 147 first transplantations from either living related (LRDs) or deceased donors (DDs) who were divided into two subgroups: rejection (RG, n = 28) and nonrejection (NRG, n = 119). Serum samples (n = 441) collected from each patient on posttransplant days 30, 90, and 180 were tested for HLA and MICA Ab using the Luminex technique.

Results

Among 82 Ab-positive patients (55.8%), 40 had both HLA and MICA, 33 only HLA, and 9 only MICA Ab in the posttransplant period. The rates of HLA class I, class II, or both Ab positivities were greater in the RG than the NRG (P = .011, .037, and .0275, respectively). At 180 days posttransplant, 64.3% of patients in the RG had Ab and 41.2% in the NRG (P = .0349). The data for the LRD (n = 116) group were similar to those for the entire group; whereas there was no significant difference in Ab positivity between RG and NRG patients who received organs from DDs. There was no significant difference with respect to HLA class II and/or MICA Ab positivity between RG and NRG among patients who lacked HLA class I Ab.

Discussion

We confirmed that HLA and MICA Ab may be harmful posttransplant, promoting rejection processes and representing an important cause of graft failure. HLA class II and MICA Ab positivities were only important predictors of graft failure when present together with HLA class I positivity. Patients who developed HLA alone or both HLA and MICA Ab rejected their grafts more frequently than Ab-negative recipients.     

抗HLA和抗MICA抗体的表达对移植肾功能和急性排斥反应的预示作用

目的 探讨抗HLA与抗主要组织相容性复合物Ⅰ类链相关基因A(MICA)抗体的表达对移植肾功能和急性排斥反应的预示作用.方法 采用免疫磁珠流式液相芯片技术检测41例肾移植受者移植前后的抗HLA和抗MICA抗体,其中37例接受了1、3、6个月及1、2、3年的动态随访.分析抗HLA和抗MICA抗体的特异性,及其与血清肌酐和排斥反应的相关性.结果 移植前共有9例(22.0%,9/41)预存抗HLA或(和)抗MICA抗体,其巾抗HLA抗体阳性2例(4.9%,2/41),抗MICA抗体阳性6例(14.6%,6/41),抗HLA和抗MICA抗体均阳性1例(2.4%,1/41).另外有5例抗MICA抗体可疑阳性.除1例的抗MICA抗体为供者特异性抗体(DSA)外,其余均为非供者特异性抗体(NDSA).37例随访者中,6例新生抗HLA抗体(16.2%),3例新生抗MICA抗体(8.1%),新生抗HLA抗体者的抗体滴度在随访3年中呈现上升趋势.9例预存抗体的受者,有4例(44.4%,4/9)发生排斥反应;6例新生抗HLA抗体的受者中,有3例(50.0%)发生急性排斥反应,而3例新生抗MICA抗体的受者均无排斥反应发生,二者间的差异有统计学意义(P＜0.05).新生抗HLA抗体产生较早(术后3 d和7 d)的2例受者均检测到抗HLAⅡ类DSA,其移植肾均因排斥反应而切除.预存抗MICA抗体,且移植后发生排斥反应者在随访的每个时间点上的血清肌酐水平均高于预存抗MICA抗体但无排斥反应者(P＜0.05);移植前抗HLA和抗MICA抗体均阴性者,术后发生排斥反应者在随访的每个时间点上的血清肌酐水平均高于抗体阴性且无排斥反应者(P＜0.01);无论是新生抗HLA抗体还是抗MICA抗体,移植后1个月发生排斥反应者的血肌酐均明显高于抗体阴性且无排斥反应者(P＜0.01).结论 预存和新生抗HLA抗体是移植后发生急性排斥反应的重要因素,而供、受者HLA和MICA基因错配是产生新生抗体的重要原因.     

主要组织相容性一类相关链A基因抗体与慢性移植肾功能减退的相关性研究

目的 探讨肾移植术后主要组织相容性一类相关链A基因(MICA)抗体对稳定期移植肾功能的影响.方法 采用免疫荧光液相芯片技术检测57例肾移植术后超过半年患者的MICA抗体水平及特异性.并同时检测SCr水平,分析MICA抗体对移植肾功能的影响. 结果 57例患者中HLA抗体和MICA抗体均为阴性者38例,HLA抗体阳性、MICA抗体阴性者11例,HLA抗体阴性、MICA抗体阳性者5例,HLA抗体和MICA抗体均阳性者3例.在MICA特异性抗体不同类型中,MICA019抗体5例、MICA027抗体3例、MICA018抗体2例、MICA004和017抗体各1例,MICA抗体阳性值≥6分者9例,占75%(9/12).MICA抗体阳性组8例与MICA抗体阴性组49例在术前输血史、淋巴毒试验、冷缺血时间、术后时间方面差异均无统计学意义(P＞0.05);而在术时年龄方面差异有统计学意义[(32.5±7.9)岁与(43.0±10.4)岁(P=0.008)3.MICA抗体阳性HLA抗体阴性组SCr水平[(117.20±12.30)μmol/L]及SCr异常比例(5/5)均高于HLA抗体和MICA抗体均阴性组[(89.40±28.95)μmol/L及23.7%(9/38),P＜0.05].结论 肾移植术后监测MICA抗体可作为肾移植HLA阴性患者预后重要的标志物,并且MICA抗体与慢性移植肾功能减退存在明显的相关性.     

Kidney Transplantation in Patients with Antibodies against Donor HLA Class II

The immunologic risk associated with donor-specific antibodies (DSA) against Class II human leukocyte antigens (HLA) in kidney transplant (KTx) recipients is unclear. The aim of this study was to determine the outcome of KTx when DSA was detected only against HLA Class II. To isolate the impact of anti-Class II DSA, we retrospectively analyzed 12 KTx recipients who at baseline had a positive B-cell flow cytometric crossmatch (FXM) and a negative T-cell FXM. Using alloantibody specification analysis, 58.3% (7/12) had DSA against donor Class II and 41.7% had no demonstrable DSA. Biopsy-proven AMR occurred in 57% (4/7) in the Class II(+) group and 0% in the Class II(-) group (p > 0.05). Peritubular capillaries stained positive for C4d in 86% (6/7) of the Class II(+) patients and in 40% (2/5) of the Class II(-) patients (p > 0.05). One patient in the Class II(+) group lost their graft at 3 months to accelerated transplant glomerulopathy, while all other grafts were functioning 3-37 months posttransplant despite the persistence of anti-Class II DSA. We conclude that KTx recipients with clearly defined anti-Class II DSA are at risk for humoral rejection suggesting that desensitization and/or close posttransplant monitoring may be needed to prevent AMR.     

Immunoglobulin class and specificity of lymphocytotoxic antibodies after kidney transplantation

The immunoglobulin class and specificity of the cytotoxic antibodies were investigated in sera collected during the first weeks following transplantation from 35 patients with functioning and 20 patients with failed grafts. No patient had had cytotoxic antibodies before the transplant, but 71.5% (25 of 35) of patients with functioning and 75% (15 of 20) of patients with failed graft subsequently developed them. The addition of dithiothreitol, which digests IgM antibodies, resulted in the disappearance of cytotoxicity in all positive sera from patients with a functioning graft. However, in the patients with failed grafts, the immunoglobulin class of the antibody varied; seven patients had only IgM antibodies, and seven had both IgM and IgG. After graft nephrectomy, IgG antibodies appeared in another six patients. In five of six patients with functioning grafts, mouse monoclonal antibodies blocked the cytotoxic activity; four with HLA-DQ monoclonal antibodies (Leu 10), one with HLA Class I (GD5). In the patients with failed grafts, blocking was seen in all nine patients studied; eight by GD5, six by Leu 10, and two by a monoclonal antibody to a monomorphic determinant of HLA-DR (100/77). Although the frequency of antibody-positive patients was similar in the successful and failed groups, the immunoglobulin class of the antibodies developed was IgM in the former group, whereas in the latter group some were IgM and others were IgG. Characterisation of the antibodies could be useful in the interpretation of a positive cross-match, since IgG antibodies are damaging to the graft whereas IgM antibodies are not.     

All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies

BACKGROUND: Recent studies show that almost all patients who have rejected a kidney transplant had human leukocyte antigen (HLA) antibodies. In this study, we sought to determine whether patients develop HLA antibodies before chronic rejection. METHODS: For the past 8 years, 139 patients who had undergone kidney transplantation were systematically examined, using an enzyme-linked immunosorbent assay-based method, for the development of class-I and class-II HLA antibodies 3 months, 6 months, and yearly after transplantation. Chronic rejection was diagnosed by biopsy. RESULTS: Among 29 patients with chronic rejection, 100% of the patients had HLA antibodies before rejection. Of these patients, 14 patients developed antibodies de novo. In contrast, among 110 patients with stable function, 27% of the patients developed HLA antibodies posttransplant (P<0.001). CONCLUSIONS: HLA antibodies were found in 29 consecutive cases of chronic rejection failures as much as one year before the loss of grafts. We conclude that HLA antibodies may be a prerequisite for chronic immunologic rejection.     

Post-transplant soluble MICA and MICA antibodies predict subsequent heart graft outcome

The objective of this retrospective study was to evaluate the role of MICA in heart graft acceptance. Pre- and post-transplant sera from 31 patients were evaluated for MICA antibodies by cytotoxicity on recombinant cell lines and soluble MICA (sMICA) concentrations by ELISA. The results demonstrated that the patients with post-transplant anti-MICA antibodies were at a high risk for the development of severe acute rejection (AR) (p<0.03; OR=8.5). However, the presence of post-transplant sMICA was found to be associated with functioning grafts without AR episodes (p<0.03, OR=7.9). In this preliminary survey, the negative association of sMICA with AR was found to be in the absence of MICA antibodies. Further research is needed to clarify the role of sMICA in allograft acceptance. Post-transplant evaluation of humoral immune response to MICA and the measure of sMICA in patient's sera may provide a good predictor of AR.     

Cold ischemia time: an independent predictor of increased HLA class I antibody production after rejection of a primary cadaveric renal allograft

BACKGROUND: Cadaveric kidneys experiencing longer cold ischemia time (CIT) are associated with higher levels of delayed graft function, acute rejection, and early graft loss. One mechanism to explain these results is that ischemia/reperfusion (I/R) injury makes the allograft more immunogenic by upregulating molecules involved in the immune response (e.g., HLA Class I/II). METHODS: We evaluated the influence of CIT on the production of HLA Class I antibody level, measured by an antihuman globulin panel reactive antibody (AHG PRA) level, in 90 unsensitized recipients of primary cadaveric renal transplants (from a total of 1442 between 1985 and 1997) who rejected their kidneys. RESULTS: By multivariate analysis, a CIT of 15 hr or more (vs. < 15 hr) independently increased the risk of the AHG Class I PRA level being > or = 20% after unsensitized patients rejected their first kidneys (relative risk=3.57; 95% confidence interval=1.26 to 10.14; P=0.01), despite the same degree of Class I/II mismatch between the two CIT groups. The overall mean peak PRA level after primary kidney rejection was significantly lower for the CIT < 15 hr group (25.9%+/-33.9; n=24) compared with the CIT > or = 15 hr group (46.3%+/-36.5; n=66) (P<0.001). CONCLUSION: Longer CIT induces a humorally more immunogenic kidney.     

The Relationship of Anti-MICA Antibodies and MICA Expression with Heart Allograft Rejection

The role of MICA antibodies in acute heart allograft rejection was examined utilizing 190 pre- and post-transplant serum samples from 44 patients collected during the first year after transplantation. MICA antibodies were detected by CDC test on recombinant cell lines and by the newly developed Luminex MICA antibody detection assay. Additionally, MICA expression was analyzed by 'real time' RT-PCR and by immunohistochemistry in 10 endomyocardial biopsies. Only two subjects had HLA antibodies post-transplant. Nevertheless, MICA antibodies were found in a significant number of subjects. The prevalence of MICA antibodies was significantly higher among those with severe acute rejection (AR) than in those without rejection (60.7% vs. 14.3%, p = 0.0038 by CDC; 55.5% vs. 5.7%, p = 0.0020 by Luminex). In most cases, the appearance of MICA antibodies post-transplant precedes AR. Following transplantation, MICA up-regulation correlated with histological evidence of severe rejection. Monitoring for MICA antibodies post-transplant may be useful to establish new risk factors for acute rejection.     

Monitoring of anti-HLA and anti-Major histocompatibility complex class I related chain A antibodies in living related renal donor transplantation

This study was undertaken with the aim to analyze the clinical relevance of posttransplant anti-HLA and anti-major histocompatibility complex class I related chain A (MICA) antibodies in response to living related donor renal transplantation. A total of 185 consecutive post-renal transplant recipient serum samples were analyzed for the detection of anti-HLA and MICA antibodies using enzyme-linked immunosolvent assay techniques. Patients carrying both anti-HLA as well as anti-MICA antibodies (MICA(+)/HLA(+)) were the worst affected, showing significantly poorer graft survival compared with the MICA-/HLA-negative group (17% vs 89%, chi(2) = 19.63, P = .000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival (P = .035 and P = .001, respectively) as compared to the nonsensitized group. The study illustrated that posttransplant monitoring antibodies to both MICA as well as HLA could be good predictors of renal allograft failure.     

Posttransplant-Alloantibodies Against MICA Antigens Associated With Decreased Long-Term Allograft Survival of Kidney Transplant Recipients

BackgroundPrevious evidence showed that antibodies against major histocompatibility complex class I-related chain A (MICA) could lead to antibody-mediated rejection in kidney transplantation in case where the patients had no alloantibodies against HLA. However, the effects of posttransplant anti-MICA antibodies on long-term renal allograft survival and function remained unsettled. We tested the posttransplant anti-MICA antibodies in 150 kidney transplant patients. The aim of this study was to compare the long-term graft survival and function between patients who were MICA positive and those who were negative.MethodsThe posttransplant serum samples from 150 patients receiving kidney transplantation in our center from 2012 to 2013 were tested for MICA antibodies and HLA antibodies by Luminex single antigen array technology. Graft survival and function were followed up for a mean time of 74.2 months. The research was conducted in accordance with the Helsinki Congress and the Declaration of Istanbul.ResultsOf the 150 patients, 38 (25.3%) were sensitized against MICA after transplantation. The anti-MICA antibodies-positive (anti-MICA+) group had a worse long-term renal allograft survival than that of anti-MICA-negative (anti-MICA–) group (P = .029), even when stratified by posttransplant HLA sensitization status or donor source. Anti-MICA antibodies also had a detrimental impact on renal allograft function, but only at 1 year posttransplantation (estimated glomerular filtration rates at 1 year: anti-MICA+ 66.6 mL/min/1.73 m² vs anti-MICA– 78.7 mL/min/1.73 m²; P = .023).ConclusionPosttransplant anti-MICA antibodies were associated with decreased long-term renal allograft survival and short-term renal allograft function.     

Relevance of MICA antibodies in acute humoral rejection in renal transplant patients

The presence of MICA antibodies was examined in eleven patients diagnosed with AHR. MICA typing was performed in both recipients and donors. Sera were collected sequentially: pre-transplant, at the AHR episode and at follow-up. Sera from 30 patients with functioning graft were also analysed. A stable MICA()008 transfected cell line was used as target to identify MICA antibodies. MICA antibodies were not detected pre-transplant nor post-transplant in patients receiving a compatible graft. MICA antibodies were detected post-transplant AHR in patients receiving an incompatible graft. The persistence of MICA antibodies was associated with chronic graft dysfunction in 3 of 4 patients in this series; although it was not always associated with the graft loss in treated AHR. None of the 30 patients in the control group with long-term functioning grafts showed antibodies to MICA()008. This report provides some insights of the relevance of MICA antibodies in AHR.     

Association of De Novo Human Leukocyte Antigen and Major Histocompatibility Complex Class I Chain-Related Gene-A Antibodies and Proteinuria With Graft Survival 5 Years After Renal Transplantation

Background

Association of de novo human leukocyte antigen (HLA) and major histocompatibility complex class I chain-related gene-A (MICA) antibodies and proteinuria with graft survival 5 years after renal transplantation. De novo presence of HLA and MICA antibodies after renal transplantation is associated with poor graft survival. Proteinuria after transplantation is also considered a risk factor for premature graft loss. In this study, we investigated the association of de novo HLA and MICA antibodies on proteinuria after renal transplantation and the association of proteinuria and de novo antibodies with graft survival.

Methods

We enrolled 275 patients without preexisting HLA and MICA antibodies followed for >5 years after renal transplantation. All donor organs were from living-related donors or from an organ donation program. HLA and MICA antibodies were detected by the Luminex method. Patients with proteinuria (>150 mg/d) underwent intermittent 24-hour proteinuria examination.

Results

The frequencies of de novo HLA and MICA antibody 5 years after transplantation were 25.8% and 12%, respectively. In total, 26.5% of patients had proteinuria at the 5-year follow-up. De novo HLA antibody was associated with increased proteinuria after transplantation (relative risk, 3.12). HLA antibody and proteinuria were both associated with poor 5-year graft survival (P = .027 and P = .006, respectively).

Conclusion

De novo HLA and MICA antibodies and proteinuria after renal transplantation are all associated with poor graft survival. De novo HLA antibody is independent risk factor for posttransplant proteinuria, and proteinuria affects the association of de novo antibodies with decreased graft survival after transplantation.     

Cardiac operation and end-stage renal disease

From 1972-1979, 22 patients with end-stage renal disease underwent 23 cardiac operations involving the pump oxygenator. Fourteen patients had coronary artery bypasss, 2 had aortic valve replacement, 2 had mitral valve replacement (MVR), 2 had MVR with coronary artery bypass, and 2 had ascending aortic root replacement with a composite graft. One patient underwent successful reoperation for a false aneurysm of the left ventricle after MVR. There were 2 postoperative deaths, for a mortality of 9.1%. The patients undergoing coronary artery bypass had an average of 2.7 grafts and an average Functional Class improvement from New York Heart Association Class III or IV to Class I to II. Eighteen patients required preoperative and postoperative dialysis to control blood volume, potassium, and uremia. Four patients had functioning renal transplants, and 4 patients underwent subsequent successful renal transplantation. We conclude that: (1) patients who have transplants and require dialysis can be successfully managed for cardiac operation in spite of their complex associated medical problems; (2) functional and symptomatic improvement simplifies continued management of the patient needing dialysis; and (3) improvement of a cardiac disability can allow favorable renal transplantation in selected patients.     

B cell positive cross-match not due to anti-HLA Class I antibodies and first kidney graft outcome

The effect of B cell cross-match (XM) was investigated in 680 first deceased-donor kidney transplants in a single centre from 1990 to 1999: 74 transplants presented a B-positive XM (Group 1) 606 had a B-negative XM (Group 2). The absence in Group 1 of weak/low-titre anti-HLA Class I antibodies was assured blocking anti-Class I reactivity by treating B cells with non-cytotoxic anti-beta2 microglobulin (alphabeta2 M) serum before XM. Graft survivals up to 5 years were not significantly different; some differences were nevertheless observed: HLA-A,B,DR mismatches influenced graft outcome in Group 1: patients with 0-2 mismatches had better survival than patients with 3-4. When analysed according DR mismatch, patients with 1 mismatch had worse graft survival than well matched patients (p<0.05). No significant difference depending on HLA match was observed in Group 2. Early acute rejection rate was similar in the Groups except the rejection episodes after one year: Group 1 had significantly more. 61/74 patients of Group 1 were retrospectively analysed for anti-HLA-DR,DQ reactivity: only 11/61 had anti-HLA-DR or DQ antibodies (3/11 were donor specific); graft survival and rejections were not significantly different in the patients with and without anti-HLA Class II antibodies. Anti-donor B cell reactivity, at XM, once excluded the presence of weak/low-titre anti-HLA Class I antibodies, did not influence first kidney graft survival.