Rate Of Acute Rejection Episodes Research Articles

Panel-Reactive Antibody Associated with Acute Rejection Episodes After Heart Transplantation: An Analysis of the UNOS Database

<h3>Purpose</h3> The presence of circulating alloantibodies can prolong transplant waiting times and may be associated with worse post-transplant outcomes. Recently, patients undergoing heart transplantation have been found to possess higher panel reactive antibody (PRA) levels, but the impact of this finding is uncertain. We aimed to determine the association between an elevated PRA and subsequent episodes of acute rejection. <h3>Methods</h3> Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed HTs performed from January 2004 to September 2020. Multi-organ transplants and re-transplants were excluded from analysis. Site-reported "Most recent PRA Class I" and "Most Recent PRA Class II" were used to assess PRA level, and the "Acute Rejection Episodes" variable was used to identify acute rejection, regardless of use of anti-rejection therapies. Detection methodology between centers could vary. Patients were stratified into three groups: 1) No-PRA (PRA% = 0), 2) Some-PRA (PRA% >0 and <50), and 3) High-PRA (PRA% >50). Rates of acute rejection were compared by log-rank test, with multivariate analysis adjusting for clinically relevant factors. <h3>Results</h3> A total of 41,537 patients were included in this study. Approximately 19% of patients experienced at least one acute rejection event. When stratifying based on Most Recent PRA Class I, the Some-PRA and High-PRA groups had significantly higher rates of acute rejection episodes, OR 1.22 (95% CI 1.12-1.33, p <0.001) and OR 1.79 (95% CI 1.55-2.06, p <0.001), respectively. Similar findings were obtained when using Most Recent PRA Class II, OR 1.31, (95% CI 1.19-1.45, p <0.001) and OR 1.71 (95% CI 1.47-1.99, p <0.001), respectively. When adjusting for sex and pre-operative blood transfusions, the results remained generally consistent - Class I: OR 3.9 (95% CI 1.04-17, p <0.05) and OR 3.2 (95% CI 0.13-37, p = 0.38), respectively; Class II: OR 3.79 (95% CI 0.94-17, p = 0.065) and OR 18.58 (95% CI 1.42-467, p <0.05), respectively. <h3>Conclusion</h3> Elevated PRA levels are associated with acute rejection episodes after HT, irrespective of patient sex and pre-operative blood transfusions. Further research should be conducted to verify our findings prospectively and account for possible confounders.

The Impact of Donor Gender on Heart Transplantation Outcomes - A Study of over 60,000 Patients in the United States

The objective of this study was to evaluate the impact of donor gender on heart transplantation outcomes in the United States. From 1987 to March 2019, 63,775 adult patients underwent heart transplantation in the United States, and their data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor gender (female, N = 11,474; male, N = 27,509) and donor menopause status (pre-menopause, ages 35-40 years old, N = 1,783; post-menopause, ages 50-55 years old, N = 1,105). The groups were propensity matched 1:1 based on year of surgery, pre-transplant status, wait list time, human leukocyte antigen matching, donor demographics, and allograft ischemic time. Paired t-test, McNemor's tests and Kaplan-Meier survival analyses were performed. The primary endpoint was all cause mortality, and secondary endpoints were postoperative complications. Propensity matching generated 15,506 patients based on donor gender and 1,094 patients based on donor menopause status. Recipients who received female donor hearts were more likely to have acute rejection episodes (630/11.9% vs. 545/10.1%, p = .007) and require post-transplant dialysis (837/10.9% vs. 719/9.3%, p = .001) than those who received male donor hearts. No difference was observed between using female or male donor hearts in the rates of graft failure (551/8.2% vs. 641/9.5%) or stroke (179/2.4% vs. 199/2.6%) (p ≥ .34). Median survival using female vs. male donor hearts was 11.6 vs. 12.1 years (p = .34) with ten-year survival of 56.5% vs. 57.1%, respectively. Recipients who received pre- vs. post-menopausal female donor hearts had similar rates of acute rejection episodes (39/11% vs. 45/12.5%), graft failure (37/7.9% vs. 46/9.9%), stroke (10/1.8% vs. 15/2.8%), or requiring dialysis (67/12.3% vs. 81/14.9%) (p ≥ .09). Median survival using pre- vs. post-menopausal female donor hearts was 11.5 vs. 10.4 years (p = .23) with ten-year survival of 56.7% vs. 51.2%, respectively. Analysis of the UNOS database showed similar median survival using female vs. male donor hearts in adult heart transplantation, irrespective of donor menopause status. Currently, female donor hearts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs.

Combined membranous glomerulonephritis and plasma cell-rich acute rejection in renal transplant recipient presented as nephrotic syndrome: case report and review of literature

Despite the contentious trials to improve the rates of acute rejection episodes and improve the renal allograft survival with potent immunosuppressants, the occurrence of more than 10 % of the inflammatory cells infiltrating renal allograft as mature plasma cells is uncommon and was recognized as plasma cell rich acute rejection (PCAR). Combination of PCAR with other glomerulopathies has not been reported before. Here, we report a case of late-onset PCAR associated with membranous glomerulonephritis (MGN) diagnosed at an early stage (2 years after transplantation). A 58-year-old male patient had end-stage kidney disease secondary to diabetic nephropathy and he was maintained on hemodialysis for 2 years until he underwent overseas living kidney transplantation. He presented to our center in Kuwait on the sixth day postoperatively, with stable renal function. He was maintained on steroid, cyclosporine, and mycophenolate mofetil. Two years after transplant, he developed picture of nephritic syndrome. His graft biopsy showed plasma cell-rich interstitial infiltrate associated with mild edema and focal tubulitis (PCACR) in addition to MGN. Further immunohistochemistry tests revealed both B-cell and T-cell markers (CD20 and CD3) were expressed in the lymphoplasmacytic infiltrate with predominant T lymphocytes. The possibility of multiple myeloma was ruled out. He received pulse steroid 1 g od for 3 days. His maintenance immunosuppression was intensified to tacrolimus-based regimen. Cluster differentiated lymphocyte count showed high CD-19 cells; therefore, we gave him a single dose of rituximab (375 mg/m2). Follow-up graft biopsy (1 month later) revealed MGN with complete resolution of plasma cells. His proteinuria started to improve after 4 months of management. He is enjoying stable graft function with controlled diabetes mellitus. PCAR is a treatable form of acute cellular rejection, and its combination with MGN will need special care with specific CD20 ablation therapy.

Successful transplantation of kidneys from deceased donors with terminal acute kidney injury

Background: There are many doubts with regards to accepting deceased kidneys with acute kidney injury (AKI) for transplantation.Purpose: The aim of this study was to present the 5-years outcome of kidney transplantation cases where deceased donors developed AKI before organ procurement.Methods: Two hundred twenty-six deceased renal transplants were analyzed. Data regarding donors and recipients were collected. Terminal AKI was defined as terminal serum creatinine concentration higher than 1.99 mg/dL and 66 such cases were diagnosed. All kidney transplant recipients were followed for 60 months.Results: AKI group presented more episodes of delayed graft function (DGF) compared to the non-AKI group (56% vs 35%, p < .05). No differences were observed between the groups in the rate of acute rejection episodes, kidney function as well as patient and graft survival.Conclusions: Transplants with AKI present more often DGF and comparable graft survival to transplants without AKI. Kidneys with AKI can be a valuable source of organs provided attentive selection and appropriate care of deceased donors.

Abstract 12052: Non-complement-Binding Donor Specific Antibodies and Cardiac-Allograft Vasculopathy in Pediatric Heart Transplant Recipients

Aim: We hypothesized that the non-complement binding of de novo donor specific antibodies (DSA) detected after heart transplant (HT) confer a lower risk for acute rejections and coronary artery vasculopathy (CAV). The purpose of this study was to compare the clinical outcomes between pediatric HT recipients with C1q+ and C1q- fixing de novo DSA Methods: 127 patients from January 2005 to December 2014 were analyzed in this study to evaluate the outcomes including acute rejections and CAV of pediatric HT recipients who had C1q+ DSA compared to those with C1q- DSA. Serum samples from patients with circulating DSA were analyzed for C1q fixing according to the manufacturer’s protocol (C1qScreen, One Lambda). Results: Out of 127 patients transplanted between 2005 and 2014, 59 (46.4%) patients developed de novo DSA, of those 37 (62.7%) had C1q+ DSA. No difference in baseline characteristics: age at HT, gender, pre-HT diagnosis of CHD, ischemic time, number of HLA mismatch and pre-HT PRA &gt;10. We found that DSA strength is significantly associated with C1q+ (C-statistics 0.89 and p &lt;0.05) and at cut off 7000 MFI has 80% sensitivity and 80% specificity. C1q positive rate varied according to DSA class type: Class I (25% C1q+), class II (66% C1q +) and Class I and II (67% C1q+). C1q+ DSA patients had 2.4 times higher rate of acute rejection episodes compared to those with C1q- DSA. C1q+ DSA patients had significantly higher rates of CAV at 10-yr post-HT compared to C1q- DSA patients (72% vs 28%) (Figure) (P&lt;0.001). C1q+ DSA patients had a trend towards poor allograft survival at 10-yr post-HT compared to C1q-DSA patients (70% vs 52%) (p =0.15). Conclusions: De novo DSA which are C1q+ have significantly greater deleterious effect on long-term allograft outcome in pediatric heart transplant recipients. Thus, measuring DSA and determining their complement binding capacity is helpful in assessing the risk of cardiac allograft vasculopathy. Figure:

Should belatacept be the centrepiece of renal transplantation?

Belatacept was developed to minimize cardiovascular risk and nephrotoxicity associated with calcineurin inhibitor (CNI)-based immunosuppression. Recently, 7-year data from the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial (BENEFIT), a phase III study comparing belatacept with cyclosporine, have been published. While during the first year of belatacept the risk of acute rejection episodes was elevated, this seemingly had marginal consequences for long-term graft survival and function as well as patient survival.For patients at a low-immunological risk, this drug seems to be a safe and effective alternative to CNI-based immunosuppression. Whether the higher rates of acute rejection episodes in the first year outweigh the gain in long-term graft function is still debated. In particular, the lower incidence of donor-specific antibodies indicates that belatacept should not be considered as lower intensity immunosuppression over the long term.Therefore, should belatacept be the centrepiece of immunosuppression for renal patients?All randomized trials so far have focussed on patients at a low immunological risk. Furthermore, cyclosporine A (CsA), the comparator of belatacept in BENEFIT and the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT), is not the CNI of choice in modern transplantation. Furthermore, while at Year 7 the rate of cancer and infections was comparable with the CsA group, long-term data are missing on safety issues for a large number of patients. Thus, currently belatacept may be the drug of choice for a select group of patients, but not for everyone.This review highlights the benefits and uncertainties of the use of belatacept in kidney transplantation.

Perioperative White Blood Cell Count as a Marker for Patient and Graft Survival after Orthotopic Liver Transplantation

Background: Orthotopic liver transplantation (OLT) is a standard procedure in end stage liver disease. However, recipients of OLT have a 10-15% risk to die within one year after transplantation. We evaluated whether different parameters of infection including inflammatory markers and white blood cells (WBC) predict post-OLT mortality, graft survival and rate of acute rejection. Methods: We collected clinical and laboratory data of 102 patients undergoing liver transplantation between 2011 and 2012 Hannover Medical School. Patients were stratified by i) patient survival, ii) graft survival and iii) episode of rejection(s) and were followed from OLT for one year. Laboratory data of peritransplant period (0-4 days after OLT) were analyzed. Results: Inflammatory markers like CRP and procalcitonin had no significant effect on one-year patient or graft survival after OLT (p=0.3 or p=0.8 respectively). Interestingly, WBC early after OLT was a prognostic marker for patients (p=0.019) and graft survival (p=0.03). Importantly, white blood cell count early after OLT was independent from rate of acute rejection episodes. White blood cell count >20.000/μl within the first four days after OLT was associated with a higher patient and graft mortality. Patient mortality was 30% (WBC >20.000/μl) in comparison to 13% (WBC <20.000/μl). These results were independent from the underlying liver disease or type of immunosuppressive regimen. Conclusions: These data demonstrate that white blood cell count >20.000/μl early after OLT is a cheap prognostic marker for patient and graft survival, while perioperative procalcitonin and CRP levels have no influence.

Pretransplant Epstein-Barr Virus Serostatus and Incidence of Posttransplant Lymphoproliferative Disorder in Pediatric Renal Transplants

Pediatric renal transplant recipients are at increased risk of Epstein-Barr virus infection which may be due to the high percentage of Epstein-Barr virus seronegative recipients at the time of transplant in the pediatric age group. We aimed to assess the Epstein-Barr virus serostatus of recipients and donors and the incidence of posttransplant lymphoproliferative disorder in pediatric renal transplant at the Labafinejad Hospital in Tehran, Iran. We reviewed the clinical records of 183 children who had a renal transplant at the Labafinejad Hospital in Tehran, Iran, between 2003 and 2011. Of all the patients, 61.2% were Epstein-Barr virus seropositive at the time of transplant. Graft survival rate and the rate of acute rejection episodes were not statistically different between the seropositive and seronegative recipients. Three patients (0.005%) had posttransplant lymphoproliferative disorder after transplant. We showed that the rate of seronegative recipients in our cohort is similar to other studies, but the rate of posttransplant lymphoproliferative disorder was low in our recipients.

Experience of Combined Liver-Kidney Transplantation for Acute-on-Chronic Liver Failure Patients With Renal Dysfunction

BackgroundThe aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction. MethodsFrom January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes. ResultsThe median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone. ConclusionsOLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low.

Comparative Study of the Cellular Pharmacodynamics of Tacrolimus in Renal Transplant Recipients Treated with and without Basiliximab

Basiliximab is a recently developed immunosuppressive agent for the prevention of acute allograft rejection in renal transplant recipients. The combination use of basiliximab and a calcineurin inhibitor was suggested to be more effective in comparison to immunosuppressive therapy using calcineurin inhibitor without basiliximab. Cyclosporine has been generally administered with basiliximab for renal transplant recipients. However, in cases of tacrolimus-based immunosuppressive regimen, the clinical efficacy and safety of combined use of tacrolimus and basiliximab remains to be elucidated. This study evaluated the tacrolimus pharmacological efficacy using a lymphocyte immunosuppressant sensitivity test (LIST) with MTT assay procedures in 16 cases of renal transplant recipients treated by tacrolimus without basiliximab and in 13 cases treated by tacrolimus in combination with basiliximab. The rate of acute rejection episodes in the recipients treated with tacrolimus plus basiliximab was 1/13 (7.7%), whereas the rate in the recipients treated with tacrolimus without basiliximab was 6/16 (37.5%). The recipients were divided into two groups according to their peripheral blood mononuclear cell (PBMC) sensitivity to tacrolimus [i.e., including a tacrolimus high sensitivity group (IC(50) <1.0 ng/ml) and a low sensitivity group (IC(50) >1.0 ng/ml). In the recipients treated with tacrolimus without basiliximab, the rate of acute rejection episodes in the tacrolimus high sensitivity group was 1/10 (10.0%), which was significantly lower than the rate in the low sensitivity group of 5/6 (83.3%; p = 0.008). The incidence of cytomegalovirus infection was not significantly different between the tacrolimus high and the low sensitivity groups of the recipients treated with tacrolimus with and without basiliximab. Therefore, in the case of selected tacrolimus-based immunosuppressive therapy for renal transplant recipients, the tacrolimus pharmacological efficacy should be evaluated using LIST at a time just before the transplant procedure in order to accurately predict allograft rejection. The data also suggested that low tacrolimus sensitivity recipients should be treated with tacrolimus-based immunosuppressive therapy in combination with basiliximab.

Pediatric Renal Transplantation in the Jordanian Population: The Clinical Outcome Measures During Long-term Follow-up Period

Recently, many international studies have suggested that pediatric patients from diverse ethnic origins confront unique challenges for transplantation. Data concerning the efficacy and safety of transplantation for various pediatric renal transplant populations remains limited and are often confounded by immunosuppressive protocols. In one study, we aimed to evaluate the short- and long-term outcomes of renal transplants in Jordanian children in comparison with groups of different nationalities. We retrospectively retrieved data for 34 Jordanian children who received kidney transplants from living donors between January 2003 and January 2009. Subsequently, we continued to follow-up with these selected patients at scheduled clinic visits to prospectively collect long-term data for a period of approximately 22 months±15 months. The patients included in this study ranged between 4 years and 19 years of age. The male/female ratio was 0.79. Glumerulonephritis (35.3%) was the most common cause of end-stage renal disease in the sample of this study; 23.5% had received a preemptive transplant. All patients also received triple immunosuppressive therapy, consisting of tacrolimus (TAC), prednisolone, and mycophenolate mofetil (n=26) or azathioprine (n=8). Furthermore, the rate of acute rejection episodes was lower in the sample of this study than the average rate of many previous studies. The patients' survival rate at 1 year, 2 years and 3 years posttransplant was nearly 100%. The corresponding graft survivals were 97.1%, 94.12% and 91.2% respectively. Beyond three years, one female patient died postgraft loss. This graft loss was mainly attributed to recurrent glomerulonephritis. Strikingly, the prevalence of posttransplant diabetes (PTD) and hypertension was higher than reported international figures. Other adverse events, such as infections, were manageable. The average result of pediatric renal transplantation in Jordan is more successful than the average results of this procedure in many developed countries, especially in terms of early graft function, acute rejection episodes as well as long-term patient and graft survivals. However, additional studies are needed to better characterize pharmacokinetic of TAC and to fully understand those factors that lead to an increased probability of developing conditions like PTD and hypertension.

Clinical Significance of the Pharmacological Efficacy of Tacrolimus Estimated by the Lymphocyte Immunosuppressant Sensitivity Test (LIST) Before and After Renal Transplantation.

The lymphocyte immunosuppressant sensitivity test (LIST) with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay procedure can predict the pharmacological efficacy of immunosuppressive agents. A previous study reported the pharmacological efficacy of tacrolimus evaluated by LIST just before renal transplantation significantly correlated with the incidence of acute rejection episodes. However, the pharmacological efficacy of tacrolimus has not been estimated after renal transplantation. Therefore, the present study evaluated the pharmacological efficacy of tacrolimus by LIST using the MTT assay procedure before and 1, 3, and 12 months after transplantation in 17 renal transplant recipients that received tacrolimus-based immunosuppressive therapy. The tacrolimus pharmacological efficacies before and after the procedure were also compared with incidence of acute rejection and cytomegalovirus (CMV) infection episodes. The individual values of tacrolimus 50% inhibition of lymphocyte proliferation (IC50) varied widely before transplantation, and the mean value of the IC50 was 126.4 ± 337.7 ng/ml. The patients were divided into two groups according to the tacrolimus IC50 values evaluated before transplantation. The rate of acute rejection episodes in the tacrolimus high-sensitivity group was significantly lower than that in the tacrolimus low-sensitivity group (p = 0.005). The tacrolimus IC50 deviation between patients expanded further at one and three months after surgery. However, the sensitivity deviation almost converged at 1 year after surgery. Moreover, the pharmacological efficacy of tacrolimus evaluated at 1, 3, and 12 months after transplantation did not significantly correlate with the incidence of acute rejection episodes. The pharmacological efficacies of tacrolimus evaluated at both before and after surgery were not significantly correlated with the episodes of CMV infection. These findings suggest that the pharmacological efficacy of tacrolimus evaluated with LIST before surgery is a useful biomarker for predicting the occurrence of acute allograft rejection in renal transplantation.

Analysis of Transplant Outcomes After Five or Six Human Leukocyte Antigen-Mismatched Living Donor Kidney Transplantation

BackgroundRecently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT). MethodsThe authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method. ResultsGraft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832). ConclusionsSurvival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT.

Liver grafts from selected older donors do not have significantly more ischaemia reperfusion injury

BackgroundThere is a general concern that aged organs are more susceptible to ischaemia. In the light of recent proposals to change the liver allocation system by expanding regional sharing, it is feared that increased cold ischaemia time of grafts from older donors may reduce graft survival. The aim of this study was to correlate donor age and the patterns of ischaemia reperfusion injury and synthetic function early after liver transplantation. MethodsWe performed a retrospective study of first transplants using a single-centre electronic database. Patterns of liver injury (based on transaminases and post-reperfusion biopsy), synthetic function (international normalized ratio [INR]), and graft and patient survival in recipients receiving liver grafts from donors aged ≥65 years (group 1, n= 50) were compared with equivalent patterns in a matched cohort of recipients transplanted with grafts from donors aged <65 years (group 2, n= 50). ResultsThere was no significant difference in transaminase levels from day 0 to day 6 after transplantation. When groups 1 and 2 were subdivided into two subgroups based on the duration of graft cold ischaemia time (<8h and ≥8h), there was no statistical difference in transaminase levels during the first 7 days. There were two cases (4%) of primary non-function in group 1 and one (2%) in group 2. Initial poor function did not differ significantly between the groups (26% vs. 24%; P= 0.81). In addition, there was no difference in histological changes in post-reperfusion biopsies (21% vs. 34%; P= 0.078) and rate of acute rejection episodes in the first year (30% vs. 32%; P= 0.99). There was no significant difference between groups 1 and 2 in 1-year patient and graft survivals (78% vs. 90% [P= 0.17]; 88% vs. 94% [P= 0.48], respectively). ConclusionsJudiciously selected livers from aged donors are not associated with major increased susceptibility to ischaemia reperfusion injury.

Induction With Basiliximab in Renal Transplantation

Introduction The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals. Objective We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals. Methods We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2). Results We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals. Conclusion In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.

Induction With and Without Antithymocyte Globulin Combined With Cyclosporine/Tacrolimus-Based Immunosuppression in Renal Transplantation: A Meta-analysis of Randomized Controlled Trials

Objective The objective of this study was to conduct a meta-analysis of randomized controlled trials (RCT) to compare the effectiveness and safety of induction with and without antithymocyte globulin (ATG) combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation. Methods Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of RCTs, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality, and then extracted data. Data were extracted for patient and graft survival, acute rejection, the incidence of Banff, cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia. Dichotomous outcomes were reported as relative risk (RR) with 95% confidence intervals (CI). Results Four RCTs (892 patients) were identified. The data showed that induction with ATG was more beneficial than no induction with ATG to reduce the incidence of chronic rejection (RR 0.70; 95% CI, 0.57–0.84) and acute rejection within 6 months (RR 0.68; 95% CI, 0.49–0.96) and at 12 months (RR 0.67; 95% CI, 0.50–0.89) as well as Banff II episodes (RR 0.53; 95% CI, 0.30–0.91), but increased the incidences of CMV infection (RR 1.61; 95% CI, 1.27–2.04) and leukopenia (RR 3.88; 95% CI, 2.80–5.38) and thrombocytopenia (RR 2.92; 95% CI, 1.77–4.04). There was no statistical difference between patient or graft survival rates at 6 and 12 months, as well as the incidences of Banff III or Banff I after transplantation. Conclusion Based on available data induction with ATG was more efficient to reduce the rate of acute rejection episodes and chronic rejection responses after renal transplantation, but was associated with increased side effects, particularly CMV infections. It is important to provide the most benefit for an individual patient.

Simultaneous combined liver and kidney transplantation: a single center experience

Renal dysfunction is common in patients awaiting liver transplantation (LT) and affects outcome following LT. Combined liver and kidney transplantation (CLKT) has been proposed as effective treatment for patients with chronic diseases of both organs, some with hepatorenal syndrome and for liver-based metabolic diseases affecting kidney. This study is undertaken to analyze results of CLKT at a single center. Of 2690 LTs performed between 1992 and 2007, there were 39 CLKTs; most common indications were metabolic, cirrhosis and polycystic disease. With follow-up of up to 170 months, 11 died (overall survival 71.8%); one-, five-, and 10-yr patient and liver graft survival is 77%, 73.7%, and 73.7%, respectively, and kidney graft survival is 77%, 70%, and 70%, respectively. Survival among metabolic group (78.6%) appeared to be better than non-metabolic group (68%); however, this difference was not significant (p = 0.39). Fifteen surviving patients (53.6%) have mild/moderate renal impairment (creatinine > or = 125 micromol/L). None has severe renal failure (serum creatinine > or = 250 micromol/L) or end-stage renal disease requiring hemodialysis. CLKT has good results in selected groups of patients. It provides protection to kidney allograft in liver-based metabolic diseases affecting kidney. The rate of acute rejection episodes of kidney is low. Significant proportion develops long-term mild/moderate renal dysfunction. Careful attention to immunosuppression to minimize nephrotoxicity may help.

Prospective, Randomized Trial on Late Steroid Withdrawal in Pediatric Renal Transplant Recipients Under Cyclosporine Microemulsion and Mycophenolate Mofetil

: Many transplant centers practice late steroid withdrawal after pediatric renal transplantation, but evidence-based data on the overall risk-to-benefit ratio in this patient population are lacking. : We therefore conducted the first prospective, randomized, open-label multicenter study to validate this strategy: 42 low-immunologic risk pediatric kidney allograft recipients, aged 10.3+/-4.3 years, on cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids were randomly assigned, more than or equal to 1-year posttransplant, to continue steroids or to withdraw over 3 months. This report contains the 1-year results. : In response to steroid withdrawal, patients experienced a significant catch-up growth with a mean standardized height gain of 0.3+/-0.1 standard deviation score (SDS) per year (P<0.05 vs. control), whereas mean height SDS in the control group did not change (0.0+/-0.1 SDS). Standardized body mass index declined significantly by 0.68+/-0.23 SDS after steroid withdrawal, but rose significantly by 0.26+/-0.34 SDS in the control group. Patients off steroids had less frequent arterial hypertension (50% vs. 87.5% (P<0.05) and significantly lower serum cholesterol (by 21%) and triglyceride values (by 36%) than control patients. Patient and graft survival were 100%. The incidence of acute rejection episodes in the steroid-withdrawal group was 1 of 23 (4%) compared with 1 of 19 (5%) in controls. Transplant function remained stable in both groups. : Late steroid withdrawal in low-immunologic risk European pediatric kidney transplant recipients on cyclosporine microemulsion and mycophenolate mofetil is not associated with an increased rate of acute rejection episodes, enables catch-up growth and ameliorates cardiovascular risk factors.

MICA Compatibility and Immunization in Third Kidney Transplantations

Significantly lower graft survival has been observed among recipients of a third (G3) compared with a first or second kidney transplantation. Because patients awaiting G3 are largely HLA immunized, they are usually transplanted with a high HLA match. Moreover, their rate of acute rejection episodes is similar to a first or second transplantation. Since major histocompatibility complex class I related chain A (MICA) molecules have been proposed as new targets for antibody recognition, we were interested to type donors and recipients for MICA alleles and to study MICA immunization of these patients. Forty-three pairs of donors and recipients were typed for MICA alleles using Luminex technology (LABtype RSSO). MICA alleles showed strong linkage disequilibrium with the B locus: some 4-digit alleles were preferentially associated with a given MICA allele. A greater frequency of patients with 2 MICA mismatches (MM) was observed among patients with rejection (40%), whereas all the graft losses were observed in patients with 0 or 1 MICA MM. MICA immunization was studied using sera from 52 patients collected on day 0 and after transplantation using a Luminex assay (LABScreen). MICA immunization was less frequent than HLA immunization, and MICA donor-specific antibody (DSA) was equally present in functional and failed grafts. These observations confirmed the potential role of MICA immunization in rejection, whereas the poor graft survival among third transplantations could not be explained by MICA incompatibility or immunization.

Steroid Elimination—Who, When, How?

Steroids have numerous side effects, many occurring early posttransplantation with relatively low prednisone doses. Consequently, investigators have attempted steroid minimization or withdrawal. The first attempts at steroid minimization used early low-dose steroids and were associated with an increased rate of acute rejection episodes, late graft dysfunction, and graft loss. Subsequent studies, with cyclosporine-based immunosuppression, attempted steroid withdrawal late posttransplantation (>3 months) in highly selected, clinically well, and immunologically low-risk recipients. Again, steroid withdrawal was associated with an increased risk of acute rejection episodes and these episodes were associated with graft dysfunction and increased graft loss. The development of new powerful immunosuppressive agents has led to renewed attempts at late prednisone withdrawal. These also have been associated with increased late rejection risk. A more exciting innovation has been the attempts at rapid discontinuation (≤7 days posttransplantation) of prednisone with the following results: (1) Randomized studies have shown no significantly increased risk of acute rejection; (2) Randomized and nonrandomized studies have shown no increase in late graft loss; (3) Successful use in living and deceased donor recipients, primary and re–transplant recipients, adult and child recipients, white and black recipients, and low-risk and highly sensitized recipients; (4) About 80% of recipients remain prednisone-free long term. Recent nonrandomized data suggest that recipients who have an acute rejection episode while prednisone free are more likely to have a second rejection episode if they are returned to prednisone-free immunosuppression. In these cases the acute rejection episode should be treated and long-term prednisone continued at 5 mg/d.