Organ Procurement And Transplantation Network/United Network For Organ Sharing Research Articles

Reexamining Transplant Outcomes in Acute Kidney Injury Kidneys Through Machine Learning.

Despite many people awaiting kidney transplant, kidney allografts from acute kidney injury (AKI) donors continue to be underutilized. We aimed to cluster kidney transplant recipients of AKI kidney allografts using an unsupervised machine learning (ML) approach. Using Organ Procurement and Transplantation Network-United Network for Organ Sharing (OPTN/UNOS) data, a consensus clustering cohort analysis was performed in 12356 deceased donor kidney transplant recipients between 2015 and 2019 in whom donors had a terminal serum creatinine ≥1.5mg/dL. Significant cluster characteristics were determined, and outcomes were compared. The median donor terminal creatinine was 2.2 (interquartile range [IQR] 1.7-3.3) mg/dL. Cluster analysis was performed on 12356 AKI kidney recipients, and three clinically distinct clusters were identified. Young, sensitized kidney re-transplant patients characterized Cluster 1. Cluster 2 was characterized by first-time kidney transplant patients with hypertensive and diabetic kidney diseases. Older diabetic recipients characterized Cluster 3. Clusters 1 and 2 donors were young and met standard kidney donor profile index (KDPI) criteria; Cluster 3 donors were older, more likely to have hypertension or diabetes, and meet high KDPI criteria. Cluster 1 had a higher risk of acute rejection, 3-year patient death, and graft failure. Cluster 3 had a higher risk of death-censored graft failure, patient death, and graft failure at 1 and 3 years. Cluster 2 had the best patient-, graft-, and death-censored graft survival at 1 and 3 years. Compared to non-AKI kidney recipients, the AKI clusters showed a higher incidence of delayed graft function (DGF, AKI: 43.2%, 41.7%, 45.3% vs. non-AKI: 25.5%); however, there were comparable long-term outcomes specific to death-censored graft survival (AKI: 93.6%, 93.4%, 90.4% vs. non-AKI: 92.3%), patient survival (AKI: 89.1%, 93.2%, 84.2% vs. non-AKI: 91.2%), and overall graft survival (AKI: 84.7%, 88.2%, 79.0% vs. non-AKI: 86.0%). In this unsupervised ML approach study, AKI recipient clusters demonstrated differing, but good clinical outcomes, suggesting opportunities for transplant centers to incrementally increase kidney utilization from AKI donors.

Effects of the implementation of acuity circle policy on waitlist and post-transplant outcomes of liver re-transplantation.

Acuity circle (AC) policy implementation improved the waitlist outcomes for certain liver transplant (LT)-candidates. The impact of the policy implementation for liver retransplant (reLT) candidates is unknown. Using Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from January, 2018 to September, 2021, we investigated the effect of the AC policy on waitlist and post-LT outcomes among patients who had previously received a LT. Patients were categorized by relisting date: Pre-AC (Era 1: January 1, 2018-February 3, 2020; n=750); and Post-AC (Era 2: February 4, 2020-June 30, 2021; n=556). Patient and donor characteristics, as well as on-waitlist and post-reLT outcomes were compared across eras. In Era 2, the probability of transplant within 90days overall and among patients relisted>14days from initial transplant (late relisting) were significantly higher compared to Era 1 (subdistribution hazard ratio [sHR] 1.40, 95% CI 1.18-1.64, p<.001; sHR 1.52, 95% CI 1.23-1.88, p=.001, respectively). However, there was no difference by era among patients relisted ≤14days from initial transplant (early relisting; sHR 1.21, 95% CI .93-1.57, p=.15). Likewise, among early relisting patients, risks for 180-day graft loss and mortality were significantly higher in Era 2 versus Era 1 (adjusted hazard ratio [aHR] 5.77, 95% CI 1.71-19.51, p=.004; and aHR 8.22, 95% CI 1.85-36.59, p=.005, respectively); for late relisting patients, risks for these outcomes were similar across eras. Our results show that the implementation of AC policy has improved transplant rates and reduced waiting time for reLT candidates listed>14days from initial transplant. However, the impact upon early relisting patients may be mixed.

Past and Present Policy Efforts in Achieving Racial Equity in Kidney Transplantation.

Purpose of ReviewInequities in transplant access for underrepresented minorities and people of low socioeconomic status persist. The central principle to organ allocation, the “Final Rule” is grounded on “equitable allocation of cadaveric organs,” regardless of background, including race/ethnicity, gender, and socioeconomic status, and there have been ongoing previous and current efforts in achieving the goal of equity in access to transplantation.Recent FindingsSome of these disparities are caused by impeded access to the transplant waiting list (i.e., lack of referral to transplantation, socioeconomic constraints) and are somewhat beyond the purview of Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy. This paper examines past and present OPTN/UNOS policy efforts that strive to make access to kidney transplantation more racially equitable.SummaryPast and current policy efforts have brought the transplant community closer to the goal of achieving equity in access to transplantation. More comprehensive data collection may aid in further understanding existing challenges.

FC 110: Survival Benefit of Preemptive Simultaneous Pancreas-Kidney Transplantation

Abstract BACKGROUND AND AIMS The evidence regarding the benefits of performing preemptive SPK (pSPK) is controversial. The aim of the present study was to evaluate the impact of pSPK on long-term patient and grafts outcomes when compared with npSPK and pKTA through a national registry study with recipients reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) registry, and to analyse the potential benefits associated with pSPK not only in patients with T1D but also in patients with T2D. METHOD To explore the survival advantage of performing a pSPK, we compared the outcomes in pSPK with nonpreemptive SPK (npSPK) recipients between 2000 and 2017 from the OPTN/UNOS registry. To account for the potential benefit provided solely by the kidney transplant, we further compared to recipients of preemptive Kidney Transplantation Alone (pKTA) with diabetes. A propensity score analysis was applied. RESULTS A total of 1522 patients received a pSPK, 7894 an npSPK and 3343 a pKTA. Overall recipient survival was superior for the pSPK group when compared with the pKTA (97.7%, and 80.9% versus 97.7% and 72.9% at 1 and 10 years, respectively, P &amp;lt; 0.001), with pKTA being associated with an increased risk of patient death [HR 1.34, 95% confidence interval (95% CI) 1.10–1.63; P = 0.003]. Estimated kidney graft survival was similar in both groups. After IPTW adjustment, pKTA was significantly associated with an increased risk of death-censored kidney graft failure (HR 1.31, 95% CI 1.09–1.56; P = 0.002). The npSPK patients presented both worse patient and kidney graft survival when compared with pSPK. CONCLUSION In conclusion, the observed survival benefit of performing an SPK preemptively reinforces the need for early referral for transplantation in patients with insulin-dependent diabetes and advanced chronic kidney disease.

Practicing With Uncertainty: Kidney Transplantation During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) pandemic required transplant nephrologists, surgeons, and care teams to make decisions about the full spectrum of transplant program operations and clinical practices in the absence of experience or data. Initially, across the country, there was a reduction in kidney transplant procedures and a striking pause in the conduct of living donation and living-donor transplant surgeries. Aspects of candidate evaluation and follow-up rapidly converted to telehealth. Months into the pandemic, much has been learned from experiences worldwide, yet many questions remain. In this Perspective, we reflect on some of the practice decisions made by the transplant community in the initial response to the pandemic and consider lessons learned, including those related to the risks, benefits, and logistical considerations of proceeding with versus delaying deceased-donor transplantation, living donation, and living-donor transplantation during the pandemic. We review the evolution of therapeutic strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their use in transplant recipients, current consensus related to immunosuppression management in infected transplant recipients, and emerging information on vaccination against SARS-CoV-2. We share our thoughts on research priorities, discuss the areas in which we are still practicing with uncertainty, and look ahead to the next phase of the pandemic response.

Effect of Mandatory 6-Month Waiting Period on Waitlist and Transplant Outcomes in Patients With Hepatocellular Carcinoma.

Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy mandates a 6-month waiting period before exception scores are granted to liver transplant candidates with hepatocellular carcinoma (HCC). This study aims to evaluate waitlist and posttransplant outcomes in patients with HCC, before and after implementation of the 6-month waiting rule. We examined two groups from the UNOS registry: Group 1 (pre-6-month rule) consisted of patients registered as transplant candidates with HCC from January 1, 2013, to October 7, 2015 (n=4,814); group 2 (post-6-month rule) consisted of patients registered from October 8, 2015, to June 30, 2018 (n=3,287). As expected, the transplant probability was higher in the first 6months after listing in group 1 than group 2 at 42.0% versus 6.3% (P<0.001). However, the 6-month waitlist mortality/dropout rate was lower in group 2 at 1.2% than group 1 at 4.1% (P<0.001). To assess regional parity of transplant, UNOS regions were categorized into three groups based on Model for End-Stage Liver Disease score at transplant: lower-score (regions 3, 10, and 11), middle-score (1, 2, 6, 8, and 9), and higher-score region groups (4, 5, and 7). Outcomes were compared from the time exception points were given, which we defined as conditional waitlist outcomes. Conditional waitlist mortality/dropout decreased, and transplant probability increased in all region groups, but the benefits of the policy were more pronounced in the higher and middle-score groups, compared with the lower-score group. The decline in waitlist mortality/dropout was only significant in the high Model for End-Stage Liver Disease group (P<0.001). No effect was observed on posttransplant mortality or percent of patients within Milan criteria on explant. The HCC policy change was associated with decreased waitlist mortality/dropout and increased transplant probability. The policy helped to decrease but did not eliminate regional disparities in transplant opportunity without an effect on posttransplant outcomes.

Editorial introductions

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Xian C. LiXian C. LiDr Xian C. Li is Professor of Immunology, Weill Cornell Medicine of Cornell University and director of Immunobiology &Transplant Sciences at Houston Methodist Hospital in Houston Texas. He also holds the Max and Lillie Frosch Centennial Chair at Houston Methodist. His lab studies the fundamental mechanisms of transplant rejection and transplant tolerance. The goal of his team is to advance transplant medicine through fundamental research. Dr. Xian Li is recognized with many awards and elected memberships; He received the American Society of Transplantation (AST) Young Investigator Award, AST Wyeth Basic Science Award, and the AST Wyeth Achievement Award. Dr. Li has served in the AST basic science advisory council, TTS basic science committee, chair of the AST Grants Executive Committee, and Chair of ATC 2018. He is an elected member of the American Society for Clinical Investigation, a standing member of the NIH study sections and DOD grant review panels. He is now an associate editor of American Journal of Transplantation and the journal of Transplantation. Linda C. CendalesLinda C. CendalesDr Linda C. Cendales, MD, is an Associate Professor of Surgery, a Duke Health Scholar, and the Director of the Vascularized Composite Allotransplantation at Duke University Medical Center. During her fellowship in Hand and Microsurgery, Dr Cendales helped organize the first VCA team in the U.S. and participated in the country's first two hand transplants in Louisville, KY. She was subsequently the first surgeon accepted into the Transplant Surgery and Immunobiology Fellowship at the National Institutes of Health (NIH). During her time at the NIH, Dr Cendales established and published a model of VCA in nonhuman primates and has one of the largest experiences in VCA in non-human primates reported in the scientific literature. She organized the first international symposium on VCA histopathology at the International Banff Conferences on Allograft Pathology leading to the published classification system now used as a standard for clinical reporting of rejection. Prior to joining Duke, Dr Cendales established the VCA program at Emory University and led the multi-disciplinary team that performed Georgia's first hand transplant in March 2011. While at Duke, Dr Cendales established the VCA program and led the multi-disciplinary team that performed North Carolina's first hand transplant and first bilateral hand transplant in May 2016 and in November 2018 respectively. Dr Cendales is the Principal Investigator of clinical and translational studies in VCA funded by the U.S. Department of Defense. Dr Cendales is an Associate Editor for the American Journal of Transplantation, is the Chair of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Vascularized Composite Allograft (VCA) Committee, and the co-chair elect of the American Transplant Congress, and the Past-President of the International Society of Vascularized Composite Allotransplantation Society (ISVCA). She has co-authored numerous scientific manuscripts, abstracts, and invited publications. Similarly, Dr Cendales has made countless presentations at national and international meetings.

Increasing Trends in Transplantation of HCV–Positive Livers Into Uninfected Recipients

The introduction of direct-acting antiviral (DAA) agents and the opioid epidemic have resulted in an increased interest in liver transplantation (LT) of organs from donors with hepatitis C virus (HCV)-related viremia.1 In March of 2015, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) implemented a policy to perform HCV nucleic acid testing (NAT) in all HCV-seropositive donors. An open-label, single-center experience with 10 patients using a multistep informed consent reported successful transplantation of HCV-seropositive viremic (HCV-V) kidneys into HCV-seronegative recipients.2 Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient.3 In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients.

The utility of 6-minute walk distance in predicting waitlist mortality for lung transplant candidates

The lung allocation score (LAS) has led to improved organ allocation for transplant candidates. At present, the 6-minute walk distance (6MWD) is treated as a binary categorical variable of whether or not a candidate can walk more than 150 feet in 6 minutes. In this study, we tested the hypothesis that 6MWD is presently under-utilized with respect to discriminatory power, and that, as a continuous variable, could better prognosticate risk of waitlist mortality. A retrospective cohort analysis was performed using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) transplant database. Candidates listed for isolated lung transplant between May 2005 and December 2011 were included. The population was stratified by 6MWD quartiles and unadjusted survival rates were estimated. Multivariable Cox proportional hazards modeling was used to assess the effect of 6MWD on risk of death. The Scientific Registry of Transplant Recipients (SRTR) Waitlist Risk Model was used to adjust for confounders. The optimal 6MWD for discriminative accuracy in predicting waitlist mortality was assessed by receiver-operating characteristic (ROC) curves. Analysis was performed on 12,298 recipients. Recipients were segregated into quartiles by distance walked. Waitlist mortality decreased as 6MWD increased. In the multivariable model, significant variables included 6MWD, male gender, non-white ethnicity and restrictive lung diseases. ROC curves discriminated 6-month mortality was best at 655 feet. The 6MWD is a significant predictor of waitlist mortality. A cut-off of 150 feet sub-optimally identifies candidates with increased risk of mortality. A cut-off between 550 and 655 feet is more optimal if 6MWD is to be treated as a dichotomous variable. Utilization of the LAS as a continuous variable could further enhance predictive capabilities.

Increasing Access.

Increasing Access.

Human Leukocyte Antigen Mismatch and Steroid Maintenance in Kidney Transplantation

BackgroundThis study aimed to analyze the impact of chronic steroid maintenance (CSM) vs early steroid withdrawal (ESW) in kidney transplant recipients (KTRs) stratified by the level of human leukocyte antigen (HLA) mismatch. MethodsAdult KTRs between 2001 and 2011 who received antibody induction followed by calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF) maintenance with or without steroid were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Using multivariate analysis, graft and patient outcomes were compared for CSM vs ESW in KTRs stratified by HLA mismatch levels separately for depleting and nondepleting antibody-induced patients. ResultsAmong 43,096 study patients, 26,582 received depleting induction (zero HLA mismatch = 5324 [CSM = 3416; ESW = 1908]; 5–6 HLA mismatch = 21,258 [CSM = 13,739; ESW = 7519]) and 16,514 patients received nondepleting induction (zero HLA mismatch = 4109 [CSM = 3453; ESW = 656]; 5–6 HLA mismatch = 12,405 [CSM = 10,890; ESW = 1515]). Adjusted graft failure risks for CSM vs ESW groups for zero HLA mismatch patients were as follows: HR 1.13, P = .07 (depleting induction); HR 1.30, P = .01 (nondepleting induction). Graft outcomes were similar for CSM vs ESW in 5–6 HLA mismatch groups for both induction types. Adjusted patient death risks were significantly higher for CSM vs ESW with depleting (HR 1.3, P = .003) and nondepleting (HR 1.45, P = .006) induction in zero HLA mismatch patients and only with depleting induction in 5–6 HLA mismatch groups (HR 1.16, P < .001). ConclusionOur study supports the feasibility of ESW regardless of the level of HLA mismatch in KTRs selected for antibody induction and CNI/MMF maintenance.

The impact of mycophenolate mofetil versus azathioprine as adjunctive therapy to cyclosporine on the rates of renal allograft loss due to glomerular disease recurrence

Given the reported efficacy of mycophenolate mofetil (MMF) in the treatment of glomerular diseases, we question whether MMF can reduce the rate of renal allograft loss due to glomerular disease recurrence compared to azathioprine (AZA) as adjunctive therapy to cyclosporine (CSA)-based immunosuppression. This is a retrospective study based on the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database designed to compare the Kaplan-Meier rates of graft loss due to disease recurrence stratified by primary renal diagnoses between recipients receiving CSA+AZA versus CSA+MMF. Recipients of primary kidney transplants (both deceased donor and living, related and unrelated) renal transplants performed between 1 January 1988 and 31 December 2007 with the primary renal diagnosis of IgA nephropathy (IgAN), membranous glomerulonephropathy (MGN), membranoproliferative glomerulonephropathy (MPGN), lupus nephritis (LN) or focal segmental glomerulosclerosis (FSGS) with a functioning allograft at discharge were included. Seven thousand eight hundred and twenty-six recipients of primary deceased donor kidney transplants (DDKT) [CSA + AZA: IgAN (890), MGN (380), MPGN (193), LN (1324), FSGS (1314) and CSA+MMF: IgAN (855), MGN (614), MPGN (116), LN (715), FSGS (1425)] and 5498 recipients of living donor kidney transplants (LDKT) [CSA+AZA: IgAN (694), MGN (229), MPGN (100), LN (592), FSGS (654) and CSA+MMF: IgAN (1066), MGN (435), MPGN (89), LN (530), FSGS (1109)] were included in the analysis. At 10-year follow-up (mean duration was 5.6 to 6.7±1.8 years in DDKT and 6.2 to 7.4±1.7 years in LDKT), mean times of transplantation (era of transplantation) were: 1992±1.6 years and 2002±1.9 years for the CSA+AZA and CSA+MMF groups, respectively. There was no statistically significant difference in the Kaplan-Meier rates of graft loss due to disease recurrence of any glomerular disease studied between the CSA+AZA and CSA+MMF groups in either DDKT or LDKT recipients. Chi-square analysis revealed no statistically significant difference between the two immunosuppressive regimen groups in terms of age, gender and ethnic background. The OPTN/UNOS database revealed no difference in the rates of renal allograft loss due to disease recurrence of IgAN, MGN, MPGN, LN and FSGS among recipients receiving either CSA+AZA or CSA+MMF maintenance immunosuppressive therapy at 10-year follow-up.

Donor-Transmitted Malignancies in Organ Transplantation: Assessment of Clinical Risk

The continuing organ shortage requires evaluation of all potential donors, including those with malignant disease. In the United States, no organized approach to assessment of risk of donor tumor transmission exists, and organs from such donors are often discarded. The ad hoc Disease Transmission Advisory Committee (DTAC) of the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) formed an ad hoc Malignancy Subcommittee to advise on this subject. The Subcommittee reviewed the largely anecdotal literature and held discussions to generate a framework to approach risk evaluation in this circumstance. Six levels of risk developed by consensus. Suggested approach to donor utilization is given for each category, recognizing the primacy of individual clinical judgment and often emergent clinical circumstances. Categories are populated with specific tumors based on available data, including active or historical cancer. Benign tumors are considered in relation to risk of malignant transformation. Specific attention is paid to potential use of kidneys harboring small solitary renal cell carcinomas, and to patients with central nervous system tumors. This resource document is tailored to clinical practice in the United States and should aid clinical decision making in the difficult circumstance of an organ donor with potential or proven neoplasia.

Organ Procurement and Transplantation Network/United Network for Organ Sharing Histocompatibility Committee Collaborative Study to Evaluate Prediction of Crossmatch Results in Highly Sensitized Patients

The requirement for a prospective crossmatch limits some organ allocation to local areas. The delay necessitated by the crossmatch restricts the distance across which offers can be made without unduly increasing the ischemia time. A collaborative study involving 14 transplant centers was undertaken by the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Histocompatibility Committee to evaluate the accuracy with which the detection of unacceptable human leukocyte antigen (HLA) antigens by most advanced solid phase immunoassays can predict crossmatch results. In addition, using actual patients' unacceptable HLA antigens, the number of compatible donors that would have been available from the OPTN deceased kidney donors during 2002 to 2004 were investigated. Panel reactive antibodies were performed by conventional or solid phase assays, and crossmatches were performed by cytotoxicity or flow cytometry. Analyses were stratified for T and B cell and by method of identifying unacceptable HLA antigens and crossmatch techniques. Combination of solid phase immunoassays and flow cytometry crossmatches resulted in a higher prediction rates of positive T cell (86.1%-93.5%) and B-cell crossmatches (91%-97.8%). Prediction of negative crossmatches based on different combination of panel reactive antibodies and crossmatch techniques varied from 14.3% to 57.1%. Furthermore, numerous potential compatible donors were identified for each patient, regardless of their ethnicity, in the OPTN database, when predicted incompatible ones were excluded. The above results showed that with the advent of solid phase immunoassays, HLA antibodies can now be accurately detected resulting in prediction of crossmatch outcome. This should facilitate organ allocation and prevents shipment of organs to distant incompatible recipients.

Donor biopsy and kidney transplant outcomes: an analysis using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database

Donor biopsy and kidney transplant outcomes: an analysis using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database

Donor Biopsy and Kidney Transplant Outcomes: An Analysis Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) Database

Although the degree of glomerulosclerosis on pretransplant donor biopsy is one criterion used in the decision to accept a deceased donor kidney, its relationship with graft survival remains controversial. This study compared graft survival with the degree of glomerulosclerosis found on donor biopsy. We also examined the agreement in degree of glomerulosclerosis between paired kidneys. Biopsy results from 12,129 adult deceased donor transplants between January 1, 2000 and December 31, 2005 were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing data, as of September 11, 2006. Of these, 2696 donors had both kidneys biopsied and subsequently transplanted. Among the groups with greater than 5% glomerulosclerosis, there was no statistically significant difference in graft survival rates (log-rank, P=0.44). The overall graft survival rates of the 0-5% group were significantly superior to those of the >5% groups (1-, 3-, and 5-year rates: 85.9%, 72.4%, and 59.0% for 0-5% group vs. 81.6%, 68.1%, and 53.6% for >5% group, log-rank P<0.001). Agreement between paired kidneys from the same donor was highest for the 0-5% glomerulosclerosis groups (90.6% for pairs with 0-5% glomerulosclerosis in the left kidney vs. 42.5% for pairs with >5% glomerulosclerosis in the left kidney). Donor kidneys with less than 6% glomerulosclerosis were associated with better graft outcomes and intrapair agreement in the degree of glomerulosclerosis. Among kidneys with greater than 5% glomerulosclerosis, the degree of glomerulosclerosis did not help predict graft outcomes. Sampling error may contribute to the lack of outcome differences seen among these kidneys, given the low intrapair agreement.

Dissociation of Depletional Induction and Posttransplant Lymphoproliferative Disease in Kidney Recipients Treated With Alemtuzumab

Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.

Post-transplant de novo malignancies in renal transplant recipients: the past and present

Post-transplant de novo malignancies are reviewed in three time periods: (i) the azathioprine (AZA) era from 1962 to 1980-1981, (ii) the cyclosporine (CYA) era (1980 to present) in which the calcineurin inhibitors, CYA and tacrolimus (TAC), were the mainstay of recipient immunosuppression, and (iii) the TOR inhibitor era starting in the year 2000. Both transplant registry and transplant center reports on malignancies occurring in the AZA era are reviewed. Reports from transplant centers and from the Cincinnati Transplant Tumor Registry (CTTR) in both the early CYA era (1980s) and the 1900-2000 CYA era are reported. Cancer incidence associated with AZA versus CYA, CYA versus TAC, and AZA versus mycophenolate mofetil (MMF) is compared in both transplant center and registry reports including new, unreported Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data from 1998 to 2003. The malignancy incidence associated with lymphocyte-depleting antibody and corticosteroid immunosuppression is discussed. Reduced malignancy incidence recently reported with TOR inhibitors is compared with that of conventional immunosuppression. Important nondrug factors influencing the incidence of post-transplant malignancies from seven single and three registry reports are detailed. The substantial role that de novo malignancies play in post-transplant mortality is discussed. Finally, management recommendations for recipients who develop de novo post-transplant malignancies are briefly presented.

Prospective Registry‐Based Observational Cohort Study of the Long‐Term Risk of Malignancies in Renal Transplant Patients Treated with Mycophenolate Mofetil

This large prospectively conducted observational cohort study examined the risk of lymphoma and other malignancies with mycophenolate mofetil (MMF) in de novo renal transplant recipients. A total of 6751 patients receiving MMF, and an equal number of matched controls receiving non-MMF-based immunosuppression, were identified from two large registries (Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) and Collaborative Transplant Study (CTS)) and followed for 3 years. The primary endpoint was development of lymphoma. Secondary endpoints included development of any malignancy. There was no evidence of any increased risk of developing lymphoma or malignancy with MMF. The risk of developing lymphoma with MMF compared with the non-MMF cohort was not higher in either the CTS registry (relative risk (95% confidence interval); 0.4 (0.17-0.94)) or the OPTN/UNOS registry (1.04 (0.61-1.78)). In the MMF group, there was a trend toward a lower risk of malignancy in both registries (OPTN/UNOS 0.86 (0.69-1.07); CTS 0.79 (0.61-1.02)) and a significant increase in time to malignancy in the CTS dataset (p < 0.026). This study has demonstrated that MMF is not associated with an increased risk of lymphoma or other malignancies post-renal transplant, and may even be associated with a lower risk in some populations.

Similar risk profiles for post-transplant renal dysfunction and long-term graft failure: UNOS/OPTN database analysis

Renal dysfunction measured by serum creatinine (>1.5 mg/dL) at 1 year post-transplant correlates with long-term kidney graft survival. The purpose of this study was to compare the risk factors for elevated serum creatinine (SCr) >1.5 mg/dL at 1 year post-transplantation, and for long-term graft failure. Between 1988 and 1999, 117,501 adult kidney transplants were reported to Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS). Of these, 96,091 were functioning at 1 year and SCr was available on 85,135 transplants. Donor and recipient demographics (age, sex, and race), transplant [living vs. cadaveric, previous transplantation, panel reactive antibody (PRA), human leukoocyte antigen (HLA) mismatch, cold ischemic time (CIT) and post-transplant delayed graft function (DGF), use of azathioprone vs. mycophenolate mofetil (MMF), cyclosporine A (CsA) vs. tacrolimus (Tac)], induction antibody, acute rejection within 1 year variables were used in the logistic regression model to estimate odds ratio (OR) for elevated 1 year serum creatinine (SCr). A Cox proportional hazard model was used to estimate the relative risk (RR) for long-term kidney graft failure with and without censoring for death with a functioning graft. Five-year actuarial graft survival for living donor transplant with SCr >1.5 and </=1.5 mg/dL at 1 year post-transplant was 83% and 88.6% (P < 0.001). The corresponding values for cadaveric transplant grafts were 66.5% and 77.9% (P < 0.001). The overall prevalence of renal dysfunction at 1 year post-transplant (SCr >1.5 mg/dL) declined from 54.5% in 1988 to 42.3% in 1999. There was a strong concordance between the key variables, such as cadaveric transplant, increasing CIT, HLA mismatch, DGF, and acute rejection, recipient race (black), younger age, and nondiabetics status; and donor race (black) and older age for elevated SCr and long-term graft failure. Donor (age), race (black), recipient race (black), immunologic variables (HLA mismatch, DGF, acute rejection) were identified as important risk factors for elevated SCr at 1 year post-transplantation and long-term graft failure. Elevated SCr should be used as a short-term marker for predicting long-term transplant survival.