Collaborative Transplant Study Research Articles

Association of Kidney Graft Loss with Posttransplant Presence of Strong HLA Antibodies Detected by Luminex Single Antigen Testing

Background: It is a matter of debate whether alloantibodies should be monitored in all kidney transplant recipients in order to combat antibody-mediated graft loss. Methods: In the Collaborative Transplant Study Serum Project, there were 64 patients with graft loss on whom a posttransplant serum 1-year before failure was available, as well as recipient and donor DNA for complete HLA typing, including HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, or -DPB1 antigens, which allowed the precise definition of donor-specific antibodies (DSA). We compared the incidence of Luminex Single Antigen (SA)-detected DSA and non-DSA antibodies in these patients with graft failure and in matched controls with functioning grafts (non-rejectors). Positivity cut-offs at 500, 1000, 2000, 3000, and 5000 MFI (mean fluorescence intensity) were analyzed systematically. Results: At cut-off 500, as many as 95% of patients with graft loss and 94% of patients without graft loss showed evidence of Luminex-detected HLA antibodies. The incidence of DSA in patients with and without graft failure was with 44% and 36%, respectively, not significantly different between the two groups. However, with increasing cut-offs the difference between the two patient groups became more pronounced. When MFI of ≥5,000 was used as cut-off for Luminex positivity, 64 patients with graft loss had a higher incidence of DSA or non-DSA antibodies than patients without graft loss (total: 59% vs. 36%; p=0.013; class I: 50% vs. 31%, p=0.047; class II: 33% vs. 14%, p=0.021; DSA: 19% vs. 9%, p=0.20; non-DSA: 56% vs. 33%, p=0.013). Importantly, as many as 67% of Luminex-positive patients with graft loss were also positive in ELISA screening, whereas this rate was only 17% in the non-rejector group. In 51 patients with graft loss, we also had a pretransplant serum which allowed the evaluation of de novo antibody production after transplantation. The rate of de novo antibodies was higher in the graft loss group than in the non-rejector group (total DSA or non-DSA: 35% vs. 14%, p=0.020; class I: 29% vs. 10%, p=0.023; class II: 18% vs. 4%, p=0.051; DSA: 8% vs. 6%, p=n.s.; non-DSA: 33% vs. 14%, p=0.034). Interestingly, at the low cut-off 500, as many as 45% of patients in the non-rejector group lost their preexisting DSA during the posttransplant course, as compared to only 25% in the graft loss group (p=0.062). Conclusion: Our data indicate that the posttransplant presence of strongly reactive HLA antibodies, especially if de novo produced, is associated with graft loss. It appears that not all Luminex-detected antibodies are detrimental. Many patients lose pretransplant weakly reactive donor-specific antibodies after transplantation and these antibodies are not associated with graft loss.

Association of Donor and Recipient Calcineurin Inhibitor Pharmacogenomic Variation with Long-Term Allograft Survival

Introduction: Calcineurin inhibitors (CNI) remain a cornerstone of renal transplantation immunosuppression. Whilst monitoring of blood CNI levels have been the traditional tool for adjusting CNI administration, it is clear that this is an imperfect strategy. Although data is conflicting, there is evidence that single nucleotide polymorphisms (SNPs) within genes involved in ciclosporin metabolism and transport are associated with ciclosporin pharmacokinetics. Less data is available in regard to polymorphisms of the donor, although small studies suggest an association between genetic variation in the ABCB1 gene and “acute ciclosporin nephrotoxicity” and allograft failure. Both focussed on the C3435T polymorphism within ABCB1, an exonic SNP for which the TT genotype is associated with reduced P-gp expression. The purpose of this study was to further assess the relationship of both donor and recipient genotype with the hard outcomes of allograft survival and mortality. Methods: Positive findings from an initial study cohort were examined in two further independent populations, in a study incorporating a total of 6169 transplant recipients and their respective donors followed for a period of up to 20 years. The initial cohort consisted of 811 Caucasian transplant donors and their respective recipients transplanted at he Queen Elizabeth Hospital Birmingham between 1996 and 2006, for which genomic DNA was available. All patients received ciclosporin and corticosteroids as primary immunosuppression, with 23% receiving mycophenolate (77% azathioprine). A comprehensive survey of sequence variation in the target genes was assessed using a “gene tagging” approach based on data from the Hapmap Project, as well as specifically investigating previously identified relevant polymorphisms. Genes studied were: CyP3A4, CyP3A5, ABCB1 (MDR1), PXR, Cyclophilin. Results: Kaplan-Meier analysis revealed that the donor ABCB1 genotype at C3435T was associated with death-censored allograft failure. Inferior outcomes were seen for kidneys from donors expressing the CC genotype. This difference persisted in a Cox proportional hazards model (donor CC versus non-CC genotype: Hazard Ratio [HR]: 1.69; 95%CI: 1.20, 2.40; p=0.003), adjusted for the following: donor age, gender, source (living versus deceased), serum creatinine, hypertension history; recipient age, race, duration of dialysis, cause of renal failure, transplant number, panel reactive anti-HLA antibodies; donor-recipient HLA mismatch. This association between donor ABCB1 genotype at C3435T was next examined in the 2 replication cohorts, the first consisting of 697 patients transplanted in Belfast, and the second consisting of 4656 recipients reported to the Collaborative Transplant Study. In neither of these cohorts was there evidence of an association between donor genotype and death-censored graft failure. No association between any other gene variants (donor or recipient) and either death-censored graft survival or mortality were seen in the Birmingham cohort, and so no attempt was made to replicate these analyses in the other cohorts. Conclusion: This study does not support the concept that either donor or recipient variation at genes relevant for CNI metabolism and transport influences the hard outcomes of kidney transplantation, and reaffirms the importance of replication cohorts prior to assigning relevance to such genetic biomarkers.

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

Inosine Monophosphate Dehydrogenase Polymorphisms and Renal Allograft Outcome

Interindividual variation in inosine monophosphate dehydrogenase (IMPDH) enzyme activity and adverse effects caused by mycophenolate mofetil (MMF) inhibition may be genetically determined, and if so, transplant recipients should receive personalized dosing regimens of MMF, which would maximize efficacy and minimize toxicity. Some studies have demonstrated a relationship between the single nucleotide polymorphism and the risk of acute rejection with IMPDH I variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others have failed to exhibit an effect. The aim of this work was to investigate the influence of these polymorphisms on acute rejection rates, graft survival and function, and MMF doses in a large cohort of patients. A random sample of 1040 recipients from the Collaborative Transplant Study DNA bank was genotyped for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052. The presence of the T (rs2278293) and G alleles (rs2278294) in the IMPDH I variants and carriage of the G allele (rs11706052) in the IMPDH II variant did not increase the risk of rejection or affect graft function by 1 year after transplantation. There was no association with MMF dose tolerated at 1 year. Furthermore, these polymorphisms did not impact graft or patient survival at 5 years. This study represents the largest cohort of patients with the longest follow-up to date and does not support previous evidence for an association between these IMPDH variants and renal allograft rejection and graft survival.

Outcome of expanded criteria donor kidneys that were transplanted at other Eurotransplant centers after being rejected by our institution

There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this means increased dialysis-associated morbidity, mortality and a reduced quality of life. The aim of this study was to ascertain whether it is justifiable for transplant centers to reject cadaveric donor organs on hand of marginal organ quality. We identified 110 kidneys that were primarily rejected for transplantation at Charité Universitätsmedizin Berlin, Campus Mitte, and later transplanted at another center within the Eurotransplant zone. Using data from the Collaborative Transplant Study, we analyzed various demographic donor data including cold ischemia times, as well as graft and recipient outcomes. The median follow-up was 54 months. The cold ischemia time averaged 16 h. The organs that were primarily rejected by our center and then transplanted at other Eurotransplant centers showed 31 % of recipients had creatinine levels under 1.47 mg/dl and 94 % had levels under 2.97 mg/dl at 3-year follow-up. The mean death-censored graft survival was 71.4 months. The mean renal transplant recipient survival was 87.5 months. Based on our findings, we propose that acceptance criteria for marginal donor kidneys need to be widened.

Treatment of Kidney Transplant Recipients With ACEi/ARB and Risk of Respiratory Tract Cancer: A Collaborative Transplant Study Report

Whether treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty-four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2-8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19-6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27-15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking.

No Association of Kidney Graft Loss With Human Leukocyte Antigen Antibodies Detected Exclusively by Sensitive Luminex Single-Antigen Testing: A Collaborative Transplant Study Report

It is unclear whether kidney transplant recipients with preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) detectable only in the highly sensitive Luminex single-antigen (LSA) assay are at an increased risk of graft failure. We studied 3148 patients who received a deceased donor kidney graft between 1996 and 2008 and were enrolled in the prospective serum project of the Collaborative Transplant Study. There were 118 patients with graft loss during the first 3 years after transplantation on whom recipient and donor DNA was available for complete HLA typing. We compared the incidence of LSA-detected DSA in these patients with graft failure and matched controls with functioning grafts. All patients were found negative in the less-sensitive complement-dependent lymphocytotoxicity and enzyme-linked immunosorbent assays. When mean fluorescence intensity (MFI) of greater than or equal to 1000 was used as a cutoff for Luminex positivity, 118 patients with graft loss did not show a higher incidence of DSA against HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, or -DPB1 antigens than 118 matched controls without graft loss (for all loci P not significant). The incidence of strong DSA (MFI ≥2000 or MFI ≥3000) detected only by LSA was low (for all loci between 0% and 5%) and did not identify unacceptable antigens that were relevant for graft loss within the first 3 years after transplantation. We conclude that, given currently practiced crossmatch procedures and immunosuppressive regimens, exclusion of donor organs carrying "unacceptable" HLA based exclusively on sensitive LSA antibody testing is not justified.

The role of pretransplant dialysis modality on renal allograft outcome

The pretransplant dialysis modality might influence renal allograft and patient survival after transplantation. Studies published to date yielded conflicting results. Deceased-donor allograft recipients reported to the 'Collaborative Transplant Study' were analysed, using multivariate Cox regression analysis, considering potential confounders which included pretransplant patient cardiovascular risk evaluation as well as immunological and treatment parameters. Primary end points were all-cause graft survival, death-censored graft survival and patient survival. In total, 60,008 recipients were analysed. Patients who were on peritoneal dialysis (PD) (n = 11,664) prior to transplantation demonstrated a 10% lower all-cause mortality (P = 0.014) but similar death-censored graft survival (P = 0.39) as recipients treated with haemodialysis (n = 45,651). This lower all-cause mortality in PD patients was primarily a consequence of a significantly lower rate of cardiovascular death with a functioning graft (P < 0.013) in a subcohort of patients defined as at increased risk. Pretransplant dialysis modality per se has no significant impact on allograft outcome. Superior all-cause survival of PD patients is primarily due to a lower rate of cardiovascular death in a subcohort of high-risk recipients. This might explain the conflicting results published to date.

Association of Mismatches for HLA-DR With Incidence of Posttransplant Hip Fracture in Kidney Transplant Recipients

Bone fractures are a frequent complication after kidney transplantation, for which various predisposing factors have been identified. It has been suggested that human leukocyte antigen (HLA) mismatch increases the risk. Data on hip fractures occurring in the first 5 years posttransplant were analyzed among kidney transplants from deceased donors performed between 1995 and 2008 and reported to the Collaborative Transplant Study. In the 20,509 patients analyzed, the cumulative rate of hip fracture by year 5 posttransplant was 0.85%. Cox regression analysis identified the following risk factors: female recipients aged 40 to 59 years (hazard ratio [HR] 2.26, P=0.029), female recipients 60 years or older (HR 5.14, P<0.001), male recipients 60 years or older (HR 2.39, P=0.028), and donor age more than or equal to 60 years (HR 1.75, P=0.009). Using the rate of fractures in recipients with zero HLA-DR mismatch as the reference, the risk of hip fracture increased for grafts with one HLA-DR mismatch to HR 1.85 (95% confidence interval [CI] 1.18-2.89, P=0.007) and with two HLA-DR mismatches to HR 2.24 (CI 1.25-4.02, P=0.007). There was a significant association between the number of HLA-DR mismatches and the diagnosis of osteoporosis 5 years after transplantation: one HLA-DR mismatch risk ratio 1.26 (CI 1.12-1.43, P<0.001) and two HLA-DR mismatches risk ratio 1.45 (CI 1.20-1.74, P<0.001). The risk of hip fracture after kidney transplantation seems to be markedly exacerbated by HLA-DR mismatching. These findings add to the growing base of evidence that HLA-DR matching influences morbidity after kidney transplantation.

Genotypic Diversity of Complement Component C4 Does Not Predict Kidney Transplant Outcome

Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effector in transplant rejection, we hypothesized that C4 genetic diversity may partially explain the variation in allograft outcomes. This retrospective study included 1969 deceased-donor kidney transplants randomly selected from the Collaborative Transplant Study DNA bank. We determined recipient and donor gene copy number of total C4, C4 isotypes (C4A and C4B), and C4 gene length variants (C4L and C4S) by quantitative real-time PCR analysis. Groups defined according to recipient C4 gene copy number (low, intermediate, and high) had similar 10-year allograft survival. Genotypic groups showed comparable rates of graft dysfunction, treatment for rejection, immunological graft loss, hospitalization for infection, malignant disease, and death. Similarly, separate analyses of C4A, C4B, C4L, and C4S; combined evaluation of donor and recipient C4 genotype; or analysis of recipients with higher risk for rejection did not reveal considerable outcome effects. In conclusion, we did not demonstrate that C4 gene copy number associates with transplant outcome, and we found no evidence that the resulting variation in the strength of classical complement activation influences susceptibility to rejection.

Impact of HLA Compatibility on Lung Transplant Survival and Evidence for an HLA Restriction Phenomenon: A Collaborative Transplant Study Report

Data concerning the impact of human leukocyte antigen (HLA) compatibility on lung transplant survival rates are limited. Using the Collaborative Transplant Study database, 5-year graft outcome according to HLA mismatch was examined in 8020 deceased donor lung transplants performed during 1989 to 2009. Graft survival rates showed a stepwise decrease as the combined number of HLA-A+B+DR mismatches increased from one to six (P<0.001). Surprisingly, the 28 grafts with 0 mismatches at all 3 loci had a 1-year survival rate of only 49.7%, significantly lower than for 1, 2, 3, 4, 5, or 6 mismatches (P=0.002, <0.001, <0.001, <0.001, 0.002, and 0.003, respectively). Multivariate regression analysis confirmed that, paradoxically, transplantation of grafts with zero HLA-A+B+DR mismatches was associated with a 19% increase in relative risk of failure. Donor lung preservation for up to 12 hr was not associated with inferior graft survival versus shorter preservation times (P=0.60). Our data show that a high number of HLA mismatches or zero mismatches impacts unfavorably on lung transplant survival.

HLA matching for organ transplantation… Why not?

HLA matching for organ transplantation… Why not?

Pediatric Kidney Transplantation: Analysis of Donor Age, HLA Match, and Posttransplant Non-Hodgkin Lymphoma: A Collaborative Transplant Study Report

The impact and relationship of donor age, human leukocyte antigen (HLA) matching, and posttransplant non-Hodgkin lymphoma in pediatric kidney recipients are not completely understood. We analyzed Collaborative Transplant Study data from 9209 pediatric kidney transplant recipients to examine the effects of donor age and HLA match on graft survival and the relationship between HLA match and occurrence of non-Hodgkin lymphoma. Survival rates using donors aged 11 to 17, 18 to 34, or 35 to 49 years were similar. Cox regression analysis showed that two HLA-DR mismatches were associated with lower graft survival in transplants performed during 1988 to 1997 (P<0.001) but not during the 1998 to 2007 period (P=0.95). A hierarchical relationship was observed for the effect of increasing numbers of combined HLA-A+B+DR mismatches on graft survival during the 1988 to 1997 (P<0.001) and the 1998 to 2007 period (P<0.001). An association between two HLA-DR mismatches and non-Hodgkin lymphoma was demonstrated by multivariate analysis (hazard ratio for 2 vs. 0-1 DR mismatches 2.04, P=0.021), and the result was consistent during both 10-year periods. We recommend that (1) kidneys from deceased donors up to 49 years be allocated to children, (2) an acceptable HLA-A+B+DR match be attempted in patients with relatively common HLA phenotypes, and (3) transplants with two HLA-DR mismatches be avoided to reduce the risk of posttransplant non-Hodgkin lymphoma.

From Cancer to Transplantation: An Evaluation of Period Analysis for Calculating Up-to-date Long-term Survival Estimates

The timeliness of survival monitoring is particularly important in a field such as transplantation medicine, where progress occurs rapidly. Period analysis, a method successfully applied for improving the timeliness of survival monitoring in population-based cancer survival analysis, could potentially be useful in the field of transplantation as well. Using data from the Collaborative Transplant Study, the authors compared the ability of traditional, cohort-based analysis methods and the period analysis method to provide timely 5-year graft and patient survival estimates for kidney, heart, and liver transplants in 6 age groups (0-17, 18-29, 30-39, 40-49, 50-59, >or=60 years) on 378 occasions between 1990-1992 and 2000-2002. Overall, period estimates provided superior predictions for the survival of most recent transplants on 344 of 378 occasions (91%); in the organ-specific analysis, this proportion ranged between 83% for heart and 100% for kidney graft survival. This evaluation provides evidence that the period analysis method can improve the timeliness of survival monitoring in solid organ transplantation. The method appears useful for providing more up-to-date long-term survival estimates than traditional methods, and its use in pertinent studies is encouraged.

Genetic Polymorphisms of Adhesion Molecules and Kidney Transplant Survival

BACKGROUND.: Adhesion molecules play a key role in the recruitment of leukocytes to sites of inflammation. Genetic polymorphisms of adhesion molecules may alter their expression or function and may thereby influence the process of leukocyte infiltration in the transplanted organ. It has also been suggested that polymorphic adhesion molecules may act as minor histocompatibility antigens. METHODS.: In two randomly selected cohorts (954 and 1002 kidney transplants), the effect of L-selectin/CD62L (codon 206 and 213), platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31; codon 125, 563, and 670), and activated leukocyte cell adhesion molecule (ALCAM/CD166; codon 258) single nucleotide polymorphisms on 5-yr allograft survival was investigated. DNA samples and clinical data were provided by the Collaborative Transplant Study. Recipients and donors were genotyped by polymerase chain reaction sequence-specific primer. A multivariate analysis was performed using a Cox regression model. RESULTS.: Incompatibility for L-selectin at codon 213 was significantly associated with better graft survival in the first cohort, but the effect could not be replicated in the second cohort. Polymorphisms of PECAM-1 and ALCAM had no impact on graft outcome. CONCLUSIONS.: This is the first comprehensive and large-scale study on the relevance of L-selectin, PECAM-1, and ALCAM genetic polymorphisms in kidney transplantation, showing no significant associations of recipient or donor genotypes with allograft survival. Because the effect of L-selectin mismatch was not reproducible, a putative role of adhesion molecules as minor histocompatibility antigens cannot be confirmed. Our results demonstrate the importance of testing large sample sizes and of performing confirmation studies to validate genetic associations.

Natural killer–cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma

AbstractPosttransplantation non-Hodgkin lymphoma is a life-threatening complication after transplantation. Although pharmacologically suppressed adaptive immunity plays a major role in its development, the role of innate immunity in posttransplantation lymphoma is unknown. We assessed the 158 V/F polymorphism in the Fc-γ receptor 3A gene (FCGR3A), killer cell immunoglobulin-like receptor (KIR) genotype, KIR ligand status, and a single nucleotide polymorphism affecting the production of interferon-γ (IFN-γ; +874 A/T) in 236 patients with posttransplantation lymphoma reported to the Collaborative Transplant Study. In addition, polymorphisms in the interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) genes previously associated with lymphoma development were also typed. Using a split-cohort approach, gene/allele frequency was related to the 5-year patient survival after the diagnosis of lymphoma and compared with 100 control solid organ transplant recipients. FCGR3A and KIR genotype significantly influenced survival after diagnosis of posttransplantation lymphoma: the hazard of dying was reduced in homozygous carriers of the high-affinity V allele (hazard ratio 0.49, 95% confidence interval 0.29-0.82, P = .006), whereas carrying a genotype including KIR2DL2/KIR2DS2 increased the risk of dying (hazard ratio 1.49, 95% confidence interval 1.07-2.05, P = .02). KIR ligands and cytokine polymorphisms had no effect on survival. None of the genetic loci analyzed emerged as risk factors for lymphoma development.

Donor‐specific transfusions

Date written: June 2007Final submission: October 2008

Transplantation of the Type 1 Diabetic Patient

Although simultaneous pancreas-kidney transplantation (SPK) is generally believed to be the treatment of choice in type 1 diabetic patients with kidney failure, there is continuing controversy whether SPK is superior to kidney transplantation alone (KTA), especially when a live donor kidney (LDK) is available. This controversy is highlighted by three recent publications authored by Young et al. (1), Weiss et al. (2), and our group (3). Analyzing data from large registries, all three studies compared kidney graft and patient survival in SPK (all from deceased organ donors) and KTA transplants, whereby the KTA grafts were from deceased (DDK) or living donors (LDK). The three studies are summarized in Table 1( bold ) with respect to data source, treatment modality, length of follow-up, and patient and kidney graft survival. Young et al. and Weiss et al. analyzed U.S. data based on the Organ Procurement and Transplantation Network/United Network for Organ Sharing and the Scientific Registry of Transplant Recipients, respectively. View this table: Table 1. Impact of glycemic control on kidney allograft and patient survival (modified from Morath and Zeier [9]) Young and colleagues found superior kidney graft and patient survival in LDK recipients as compared with SPK recipients after a maximum of 7 years of follow-up. No significant difference was found between deceased donor SPK and DDK patients with respect to kidney graft and patient survival. In contrast, analyzing the international Collaborative Transplant Study (CTS) database, which collects data from 46 countries in five continents, our group found that SPK and LDK yielded clearly superior kidney graft and patient survival as compared with DDK alone. Importantly, in the CTS analysis, patient survival beyond year 10 after transplantation in SPK recipients was significantly better than that of recipients of a LDK without a pancreas graft (hazard ratio = 0.55; P = 0.005), as demonstrated for transplants …

Outcomes of kidney transplant tourism in children: a single center experience

Transplant tourism is a necessity for children with end-stage renal disease living in regions without established local transplantation programs. The use of kidneys from living unrelated donors (LURDs) was common practice in Asia prior to the recent global condemnation of commercial organ transplantation. Objective information on the outcomes of pediatric transplant tourism is scarce. Here, we report the Dubai experience with 45 renal allograft transplantations performed outside the United Arab Emirates (UAE) between 1993 and 2009. Transplantation from 33 LURDs, ten living related donors (LRDs) and two deceased donors was performed in 14 different countries. The mean number of human leukocyte antigen (HLA) A/B/DR allele matches was 1.4 +/- 0.8 in the LURD graft recipients and 3.9 +/- 0.7 in the LRD recipients. Outcomes were compared with those of a matched group of 3,150 pediatric LRD transplantations from the Collaborative Transplant Study (CTS). Ten-year patient survival was 100% in the LRD patients, 91.2% in the LURD patients, and 92% in the CTS patients. The three deaths in the LURD group occurred within the first 4 months after transplantation and were related to acute rejection. One-year and 10-year graft survival was 100% in the LRD group and 94.8% and 66.7% in the CTS-LRD groups, vs 87.8% and 43.4% in the LURD group. Major viral infections [Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella zoster (VZV)] were four-times more common in patients that had received LURD grafts than in those that had received LRD grafts. In conclusion, whereas LRD kidney transplantation performed abroad yields excellent long-term results, transplantation of LURD kidneys is fraught with a high complication rate affecting graft and even early patient survival.

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant

Posttransplant Lymphoproliferative Disorder Following Kidney Transplant