Impact of transfusions and acute rejection on posttransplantation donor antigen-specific responses in two study populations. Cooperative Clinical Trial in Transplantation Research Group

BACKGROUND: We participated in a protocol supported by the National Institutes of Allergy and Infectious Disease, Cooperative Clinical Trial in Transplantation (CCTT), which was designed to investigate the effect of peritransplant donor-specific transfusion in non-HLA-identical living donor kidney recipients. METHODS: We determined the donor antigen-specific responses at 1 year after transplantation for the 79 CCTT donor-recipient combinations in this study. A lower rate of donor antigen-specific hyporeactivity was seen in the CCTT recipients (6 of 79=8%) versus our recipients at the University of Minnesota who underwent transplantation in the same period (9 of 55=16%, P=0.16) and versus our combined historical data (33 of 131=25%, P=0.002). Therefore, we studied the differences in the two recipient populations to determine why hyporeactivity was lower in the CCTT group than at our center. RESULTS: Significant differences were seen in the acute rejection rates and the frequency of pretransplantation random transfusion. Overall and early (<3 month) acute rejection rates were higher in CCTT versus Minnesota recipients (overall: 51% vs. 20%, P=0.001) (early: 43% vs. 16%, P=0.001). The frequency of pretransplantation random transfusion was 40% for CCTT recipients (34%) versus 80% for Minnesota recipients (75%) (P=0.0004). CONCLUSIONS: These results provide provocative, although not conclusive, evidence for the importance of pretransplantation transfusion and acute rejection episodes in the development of donor antigen-specific hyporeactivity. Pre-, peri-, and posttransplantation clinical events undoubtedly have an impact on posttransplantation immune parameters.     

Association of HLA phenotypes of end-stage renal disease patients preparing for first transplantation with anti-HLA antibody status

Patients with pre-transplantation high levels of panel reactive antibody (PRA) have an increased risk of graft failure, and renal transplantation in sensitized patients remains a highly significant challenge worldwide. The influence of anti-human leukocyte antigen (HLA) antibodies on the development of rejection episodes depends on patient-specific clinical factors and differs from patient to patient. The HLA typing of the recipient might influence the development of anti-HLA antibodies. Some HLA antigens appear to be more immunogenic than others. The aim of this study is to demonstrate the distribution of HLA phenotypes in PRA-positive and PRA-negative end-stage renal disease (ESRD) patients on the basis of having sensitizing events or not. Our study included 642 (mean age: 41.54; female/male: 310/332) ESRD patients preparing for the first transplantation and who are on the cadaveric kidney transplantation waiting list of Istanbul Medical Faculty in 2008–2009. Class I HLA-A,B typing was performed by complement-dependent cytotoxicity (CDC) method, whereas class II HLA-DRB1 typing was performed by low-resolution polymerase chain reaction (PCR)-sequence-specific primer (SSP). All serum samples were screened for the presence of IgG type of anti-HLA class I- and II-specific antibodies by enzyme-linked-immunosorbent assay (ELISA). PRA-negative group consisted of 558 (86.9%) and PRA-positive group included 84 (13.1%) patients. We have found statistically significant frequency of HLA-A3 (p = 0.018), HLA-A66 (p = 0.04), and HLA-B18 (p = 0.006) antigens in PRA-positive patients and DRB1*07 (p = 0.02) having the highest frequency in patients with sensitizing event history but no anti-HLA development suggesting that DRB1*07 might be associated with low risk of anti-HLA antibody formation.     

预防预致敏受者尸体肾移植术后急性排斥反应的临床研究

目的 探讨HLA配型及新型免疫抑制剂治疗方案对预防致敏患者肾移植术后急性排斥反应的影响.方法 实验组选择46例术前致敏患者(术前PRA>10%),对照组选择同期705例未致敏患者(术前PRA<10%),实验组患者均采用诱导治疗(ATG 100 mg/d,5～7 d)+三联免疫抑制剂维持治疗方案(FK506+MMF+激素),比较两组间患者术后急性排斥反应发病率、移植肾功能延迟恢复比例、移植肾/患者一年存活率,同时分析HLA配型对移植肾急性排斥反应的影响.结果 实验组与对照组急性排斥反应的发病率分别为30.43%和19.57%(P<0.05);移植肾功能延迟恢复发病率分别为60.86%和11.87%(P<0.01).患者一年存活率分别为95.65%和98.44%,一年移植肾存活率分别为93.48%和96.88%;一年时平均血肌肝分别为130 mmol/dL和125 mmol/dL,差异无统计学意义.实验组患者HLA相配率(4.2)明显高于对照组患者(2.8)(P<0.05).实验组中HLA配型2-4错配的患者与0-2错配患者的急性排斥反应发病率有显著性差异,高度致敏患者(移植术前PRA>50%)急性排斥反应发病率较低度致敏患者(PRA 10%～20%)发病率高,移植术后PRA水平持续升高者更容易出现急性排斥反应.结论供、受者之间良好的HLA配型及采用新型免疫抑制药物治疗方案,对预防及减轻致敏患者移植术后急性排斥反应疗效确切.     

Effect of recipient sensitization (peak PRA) on graft outcome in haploidentical living related kidney transplants

OBJECTIVE: To evaluate the influence of pre-transplant recipient sensitization on the outcome of 1-haploidentical live related donor (LRD) kidney transplants. METHOD: We reviewed 141 consecutive cyclosporine-treated adult haploidentical first transplants for which panel reactive antibody (PRA) levels were available. Patients were divided into three groups according to their peak PRA levels: group I, PRA = 0 (n = 97); group II, PRA = 1-50% (n = 24); and group III, PRA = 51-100% (n = 20). RESULTS: Differences in PRA were associated with significant differences in short- and longer-term graft survival, unrelated to patient survival. Graft survival at 1, 3, and 5 yr was only 74, 40, and 27% in group III, compared to 92, 87, and 52% in group II, and 96, 91, and 85% in group I (p < 0.001). Increasing PRA was associated with shorter time-to-graft failure. In group III, 20% lost their transplant from acute rejection in the first 6 months, versus 4% in group II and 3% in group I (p < 0.01). Graft survival in group II diverged from that of group I only after 3 yr, due to an increase in loss from chronic rejection. Hospitalization was longer in group III, in association with a significantly higher incidence of acute rejection during the first 3 months after transplantation (p < 0.02). Serum creatinine was higher in sensitized than nonsensitized patients at all time points. CONCLUSIONS: Sensitization has a significant negative impact on the outcome of haploidentical LRD kidney transplants. Sensitized potential recipients and their potential donors should be aware of this in arriving at informed decision-making for transplantation. These patients may benefit from more sensitive cross-match testing, more intense or more novel immunosuppression, or immunomodulation to modify their immune responsiveness.     

High pretransplantation soluble CD30 levels: impact in renal transplantation

In a retrospective study, the impact of the level of pretransplantation soluble CD30 molecule (sCD30) was evaluated on 3 year transplant survival, as well as the number and grade of acute rejection episodes among kidney recipients engrafted between 2000 and 2002. One hundred and ninety sera of 190 patients sampled on the cross-match day were tested for sCD30 concentrations using an enzyme-linked immunosorbent assay (ELISA) kit (Biotest). For the analysis, a sCD30 cutoff level of 100 U/mL was chosen: 87 (46%) recipients had a level >100, and 103 (54%) <100. All cases (5) of immunological graft loss showed a high sCD30 level. The rate of biopsy-proven acute rejection was 26% in the sCD30 >100 group versus 22% in the sCD30 <100 groups. Among the first graft population (n = 157), the rate was 27% for sCD30 >100 versus 20% for the lower level. The difference was more important for grade II acute rejection (Banff criteria): 6/87 (7%) showed high sCD30 versus 2/103 (2%) with sCD30 <100. This analysis became significant for anti-HLA immunization: 11 (13%) recipients developed anti-HLA class II antibodies in the first group (sCD30 >100) versus 1 (1%) in the second group (sCD30 <100; P < .01). A high pretransplantation sCD30 was not a significant risk factor for an acute rejection episode, but it seemed to be more predictive for antibody-mediated acute rejection and immunological graft loss. However, many recipients showed an increased pretransplantation concentration without any rejection episode or graft loss. Consequently, sCD30 pregraft measurements cannot be used as a predictor for acute kidney rejection among our transplant center, nor as an aid to adapt the immunosuppressive regimen.     

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.     

Effect of Pretransplantation Body Mass Index on Allograft Function and Patient Survival After Renal Transplantation

We evaluated the effects of pretransplantation recipient body mass index (BMI) on allograft survival and on kidney function. Kidney transplant recipients were grouped according to their pretransplantation BMIs: Group I (BMI <18.5 kg/m²; n = 10); Group II (BMI 18.5-24.9 kg/m²; n = 62); Group III (BMI 25.0-29.9 kg/m²; n = 47); and Group IV (BMI >30.0 kg/m²; n = 16). Excellent 1-year patient and graft survival rates were observed in all groups. Increased BMI was associated with increased hypertension and longer hospital stays. The incidence of acute rejection episodes, slow graft function, and delayed graft function, as well as the need for antithymocyte globulin Fresenius (ATG-F) rescue therapy were comparable between the 4 patient groups. The 1-year glomerular filtration rate was markedly different between the 4 patient groups. The 1-year posttransplantation glucose level was higher among obese patients compared with the other groups. A multivariate regression analysis confirmed the association of a higher 1-year GFR with obesity (BMI >30.0 kg/m²). Overweight and obese recipients showed excellent long-term patient and graft survival rates. Accordingly, denying patients renal transplantation because of obesity may not be justified.     

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (<6 months) acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.     

肝移植术后致敏状态的监测

目的　探讨肝移植受者致敏与移植物功能的关系。方法　采用酶联免疫吸附法(ELISA)对 15例患者肝移植前后的群体反应性抗体 (PRA)进行动态监测。结果　 15例患者肝功能的主要指标 ,包括丙氨酸转氨酶、总胆红素、直接胆红素等大多在术后 1周内恢复正常。 15例中有 1例术前中度致敏 ,术后发生轻度排斥反应 1次 ,经治疗后逆转 ,其PRA在观察期内一直保持阳性。另外 14例受者移植前、后PRA均阴性 (PRA <10 % ) ,其中 1例发生排斥反应 1次 ,但PRA仍保持阴性。结论　肝移植受者的致敏状态与术后的排斥反应密切相关。     

Management of biliary tract disease in heart and lung transplant patients

BACKGROUND: Preexisting gallstones and pharmacologic alterations in both bile lithogenicity and immune function may predispose organ transplant recipients to the complications of biliary calculi. METHODS: Records of all 178 patients undergoing heart, lung, or heart-lung transplantation at our institution between 1980 and 1998 were reviewed. Patients with biliary tract disease were grouped as follows: group I, pretransplantation diagnosis and treatment; group II, pretransplantation diagnosis and posttransplantation treatment; group III, normal pretransplantation biliary tree with posttransplantation diagnosis and treatment; group IV, unknown pretransplantation biliary status with posttransplantation diagnosis and treatment. Comparison among groups was made with regard to ultrasound findings, presentation, indication for operation, procedure, and outcome. RESULTS: Of the 141 patients undergoing pretransplantation and/or posttransplantation ultrasound surveillance, the prevalence of abnormal ultrasonography was 36%. All patients in group I (n = 11) underwent elective intervention without complication. Of the 14 patients (groups II through IV) undergoing posttransplantation operation, intervention was mandated by acute complications of biliary tract disease in 7. The mortality rate in these 7 patients was 29%. CONCLUSIONS: Cholecystectomy in the posttransplantation period is often required emergently and has a high mortality. Posttransplantation surveillance of the biliary tree is crucial because of the high rate of de novo stone formation. All biliary calculi should be eradicated electively in stable patients before transplantation and on diagnosis after transplantation.     

Hepatitis C, acute humoral rejection, and renal allograft survival

The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR. When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status, HCV was not a statistically significant predictor of allograft loss. HCV was also associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab-positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was notably attenuated and no longer statistically significant.     

Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation

The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.     

Effect of simvastatin in the treatment of highly sensitized dialysis patients: the pre and post-renal transplantation follow-up outcomes

The graft survival rates of sensitized kidney recipients have been shown to be lower than non-sensitized patients. Therefore, panel reactive antibody (PRA) and cross-match determination is accepted as mandatory screening for renal transplantation candidates. Our recent previous study has shown that simvastatin had a significant immunosuppressive effect in PRA-positive and/or crossmatch-positive patients. We present the pre and post-transplantation follow-up outcomes of simvastatin treatment in the highly sensitized dialysis patients. Thirty patients were followed for a mean period of 26 months. The PRA and flow cytometric measurements were performed at monthly intervals. Ten patients underwent successful kidney transplantation (eight living-related and two cadaveric). None of the patients developed hyperacute or acute rejection, and there was no graft loss during 19.8+/-6.2 months of post-transplantation follow-up. Of the 18 patients who stayed on dialysis throughout the study with PRA positivity, six were lost to follow-up and three spontaneously stopped taking the simvastatin. In the latter three cases, the PRA levels rose significantly after the drug was discontinued. Eight of the remaining nine PRA-positive patients showed significant drops in mean PRA level over the study period, and entered the range considered acceptable for transplantation. Only one patient showed persistently high PRA levels throughout the study. In one patient, the drug had to be discontinued due to acute toxic hepatitis. In conclusion, the results indicate that continuous simvastatin therapy effective in immunized and highly sensitized dialysis patients. Meanwhile, it has beneficial effect on 1-year graft survival in sensitized renal transplantation group.     

Successful third kidney transplantation with intensive immunosuppression in a highly sensitized recipient

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.     

Clinical significance of posttransplantation vesicoureteral reflux during short-term period after kidney transplantation

BACKGROUND: Urinary tract infection (UTI) may occur in the form of asymptomatic bacteruria but severe cases may cause life-threatening pyelonephritis or sepsis in immunosuppressed kidney transplant recipients. Vesicoureteral reflux (VUR) is one risk factor in the transplanted kidney. But controversy exists regarding the effect of VUR in terms of graft outcomes. The objective of this study was to analyze the clinical outcomes among patients with posttransplantation VUR. PATIENTS AND METHODS: Between April 2005 and June 2006, we examined 75 patients with functioning grafts for more than 1 year by voiding cystourethrography at 1 year for the grade of posttransplantation VUR: group A, absent (n = 28) including grade I (n = 6) and II (n = 22); group B, including grade III (n = 17) and IV (n = 2). Patient characteristics included etiology of end-stage renal disease, duration of dialysis before transplantation, serum creatinine, creatinine clearance at 1 and 12 months after transplantation, and postoperative complications. The presence/absence of UTI, acute rejection, and graft loss were compared for significance. RESULT: Posttransplantation VUR present in 47/75 patients (61.3%) was over grade III in 19 patients. There was no difference in significant risk factors between the groups as well as between the reflux subgroups. VUR did not influence graft function with the only significant factor being acute cellular rejection. CONCLUSION: We failed to confirm a risk of developing posttransplantation VUR. Posttransplantation VUR did not negatively affect graft function; acute cellular rejection was the only factor that influenced it. Longer follow-up needs to be performed to clarify the long-term effects of posttransplantation VUR on graft function.     

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection

BACKGROUND: Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. METHODS: We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. RESULTS: Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). CONCLUSIONS: sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.     

sCD30 and neopterin as risk factors of chronic renal transplant rejection: impact of cyclosporine A, tacrolimus, and mycophenolate mofetil

High pretransplantation sCD30 levels have been shown to be associated with lower 5-year kidney graft survival in mainly Cyclosporine A (CsA)-treated recipients (Collaborative Transplant Study database). To analyze the effect of different immunosupressive regimens (CsA/Azathioprine [Aza], CsA/Mycophenolate Mofetil [MMF], Tacrolimus [Tacr]/Aza) on sCD30, we assessed serum sCD30 and neopterin together with in vitro cytokine responses in a prospective randomized study of 84 renal transplant recipients before, 4 months, and 1 year after transplantation. Panel-reactive antibody (PRA) formation, HLA matching, ATG induction therapy, and acute rejections had no impact on sCD30 levels, whereas cytomegalovirus (CMV) infections induced an up-regulation of sCD30 4 months posttransplantation (P = .003). Whereas MMF showed no effect on sCD30 compared with Aza therapy, we found a significant impact of Tacr versus CsA treatment (1-year sCD30 ≥60 U/mL: 14/42 (33%), CsA; 1/38 (3%), Tacr; P < .0005). Chronic rejection 2 years posttransplantation was associated with elevated 1-year sCD30 (P = .001) and neopterin levels (P = .006). Our data indicate that the Th2 activation marker sCD30 provides a risk factor for chronic rejection independent of classical immunological risk factors and may be down-regulated using Tacr treatment.     

Pre-emptive transplants for patients with renal failure: an argument against waiting until dialysis

BACKGROUND: Pre-emptive kidney transplants have not been favored in some centers because of concern about possible increased noncompliance and allegedly inferior long-term results. We analyzed our experience with pre-emptive kidney transplants to determine whether such concerns are justified. PATIENTS AND METHODS: Between January 1, 1984, and June 30, 1998, we performed 1849 adult primary kidney transplants: 385 pre-emptive (recipients not undergoing dialysis, ND) and 1464 non-pre-emptive (recipients undergoing dialysis, D). Results were subdivided by donor source: cadaver (CAD) and living donor (LD). ND recipients tended to be younger, but otherwise, the two groups were similar. Posttransplantation quality of life in recipients was evaluated using the nationally standardized Short Form Health Survey (SF-36). The posttransplantation employment status of the recipients was also evaluated. RESULTS: The patient survival rate 5 years posttransplantation was significantly better for ND (vs. D) recipients for both CAD (92.6% vs. 76.6%, P=0.001) and LD (93.3% vs. 89.5%, P=0.02) transplants. The 5-year patient survival rate was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation for both CAD (P=0.0005) and LD (P=0.0001) transplants. The graft survival rate 5 years posttransplantation was similar between ND and D recipients for CAD transplants, but significantly better for ND (vs. D) recipients of LD transplants (92.3% vs. 84.8%, P=0.006). For CAD transplants, the 5-year graft survival rate was not different when ND recipients were compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation; for LD transplants it was significantly higher for ND recipients compared with recipients undergoing dialysis for < 1, 1-2, and > 2 years pretransplantation (P=0.04). The incidence of acute and chronic rejection was no different between ND and D recipients for either CAD or LD transplants, and it was also not affected by the pretransplantation time undergoing dialysis. Graft loss secondary to the recipient's discontinuation of immunosuppressive therapy (a crude estimate of compliance) was similar between ND and D recipients. Five years posttransplantation, the SF-36 scores regarding the recipient's quality of life and the employment status were similar for ND compared with D recipients, regardless of donor source. CONCLUSIONS: ND recipients do not seem to have higher rates of noncompliance than D recipients. Results for ND recipients seem to be superior than for D recipients, supporting the contention that renal failure patients should, if possible, undergo transplantation before dialysis.     

Chronic rejection in primary renal allograft recipients under cyclosporine-prednisone immunosuppressive therapy

Although the introduction of cyclosporine-prednisone immunosuppression has improved early renal graft survival, chronic rejection remains a major cause of longterm graft dysfunction. This study retrospectively examined 69 cases of chronic rejection among 643 primary renal allograft recipients treated with cyclosporine-prednisone immunosuppression from July 1981 to October 1989. Chronic rejection was defined as a rejection episode diagnosed greater than 90 days posttransplantation with characteristics of progressive nonacute renal function deterioration, confirmed, in most cases, by renal biopsy. This group was compared with an equal-sized matched cohort. Among cadaveric recipients, 61 of 456 patients (13.4%) displayed chronic rejection, whereas among living-related recipients, 8 of 187 patients (4.3%) developed chronic rejection. The average time from the date of transplantation to diagnosis of chronic rejection was 15 +/- 14 months. One- and three-year graft survivals following diagnosis of chronic rejection were 51% (30/59) and 25% (13/51), respectively, compared with the cohort one- and three-year graft survivals of 98% (58/59) and 86% (32/37) at similar periods posttransplantation. HLA mismatch, PRA status, blood transfusion history, lipid levels, cyclosporine trough levels, incidence of prior acute rejection, and initial graft dysfunction were not significantly different between the chronic rejection group and the matched cohort. Hypertension and proteinuria were significantly associated with chronic rejection (P less than 0.001). Of 58 biopsies performed, findings solely consistent with chronic rejection were observed in 9 cases (15%) and "acute upon chronic" rejection in 49 cases (83%). Treatment of acute concomitants improved the renal function in 43% (27/63) by the time of hospital discharge. Nonetheless, at 12 months the incidence of improved renal function eroded to 22% (13/59), suggesting that the benefit was relatively short-lived. Although the overall incidence of chronic rejection in this group of cyclosporine-prednisone-treated patients was lower than previous azathioprine-prednisone cohorts, the clinical presentation and progression of chronic rejection was similar. Additionally, the incidence of chronic rejection within this series was lower among living-related recipients versus cadaveric recipients of donor organs.     

Graft-protective role of high pretransplantation IgA-anti-Fab autoantibodies: confirmatory evidence obtained in more than 4000 kidney transplants. The Collaborative Transplant Study

BACKGROUND: Preliminary studies showed an excellent success rate of kidney grafts in patients with high pretransplantation serum levels of IgA autoantibodies directed against the Fab region of the human IgG molecule. METHODS: With the collaboration of 30 centers from around the world, we attempted to verify the role of IgA-anti-Fab autoantibodies in kidney transplantation in an entirely new series of 4316 cadaveric kidney transplants, with special consideration of presensitized and poorly HLA-matched recipients. RESULTS: In agreement with previously published preliminary findings, 147 recipients with a high pretransplantation IgA-anti-Fab of >1000 had a 2-year kidney graft survival rate of 88+/-3% (+/- SE), compared with an 80+/-1% rate in 851 recipients with a low IgA-anti-Fab of <60 (P = 0.02). Even in patients at an increased risk of graft rejection, high pretransplantation IgA-anti-Fab autoantibody activity was associated with superior graft survival. Among 815 presensitized patients, 31 had a high pretransplantation IgA-anti-Fab activity of >1000 and their 2-year graft survival rate was 94+/-4%, in contrast to a 71+/-4% rate in 165 presensitized recipients with a low IgA-anti-Fab of <60 (P = 0.02). Of 2294 recipients who received a kidney with > or =3 HLA-A+B+DR mismatches, 79 recipients had a high pretransplantation IgA-anti-Fab of >1000 and a 2-year graft survival rate of 90+/-4%, as compared with a 79+/-2% rate in 459 patients with a low IgA-anti-Fab of <60 (P = 0.04). CONCLUSIONS: The present study confirms that kidney graft recipients with high pretransplantation IgA-anti-Fab activity have excellent graft survival, and it extends this observation to presensitized recipients and poor HLA matches.