Joseph F. Magliocca

Extracorporeal support for organ donation after cardiac death effectively expands the donor pool.

Background:We sought to evaluate the effect on short-term outcomes of normothermic, extracorporeal perfusion (ECMO) for donation of abdominal organs for transplantation after cardiac death (DCD). Study parameters included increase in number of donors and organs, types of organs procured, and viabili

The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation.

Alemtuzumab is a monoclonal anti‐CD52 antibody, which has been used extensively off label in solid organ transplantation. Its primary use has been as an induction agent at the time of organ transplantation, although there is limited experience using it to treat steroid‐resistant rejection. Prolonged lymphocyte depletion can be expected following alemtuzumab treatment even with one dose of 30 mg intravenously. The nature and kinetics of lymphocyte repopulation depend on the maintenance immunosuppression being administered. In comparison with Thymoglobulin, a polyclonal depleting antibody preparation, alemtuzumab offers significant practical benefits with lower cost, fewer side effects in administration, and no specific issues with i.v. access. The risks and benefits of depleting induction agents, such as alemtuzumab, are compared with nondepleting agents, such as anti‐CD25 induction therapy. While the majority of experience in solid organ transplantation has been in kidney transplantation, there is more limited experience in liver, pancreas, islet, small bowel, and lung transplantation. We herein review some of the lessons learned from clinical experience to date in solid organ transplantation using alemtuzumab as an immunosuppressant.

Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States

There has been a notable rise of BK virus among kidney transplant recipients. Single‐center reports have identified risk factors for development of BK virus. However, there has not been an assessment of risk factors and incidence of this complication at a national level. This study utilized newly collected follow‐up information from the national SRTR database to investigate incidence, risk factors and outcomes for solitary kidney transplant recipients associated with treatment for BK virus (TBKV) from 2004 to 2006. Logistic and Cox models were utilized to assess risk factors and evaluate graft survival associated with TBKV. Incidence of TBKV was 1.6% at 6 months and 2.6% at 1 year following transplantation. Patients with and without TBKV at 6 months had 79% and 90% 3‐year overall graft survival respectively. Risk factors included advanced donor age, pediatric, African American and male recipients, human leukocyte antigen‐mismatching and tacrolimus and thymoglobulin induction as baseline immunosuppression. Acute rejection episodes were more frequent prior to and following TBKV. TBKV is a common and rising incidence, varies based on transplant characteristics and should be included as a safety endpoint in studies investigating immunosuppressive protocols. Careful monitoring and further understanding of disease etiology and treatment strategies are needed.

Impact of Cold Ischemia Time on Graft Survival Among ECD Transplant Recipients: A Paired Kidney Analysis

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17 514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14 230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1–3 h (p = 0.90), 4–9 h (p = 0.41), 10–14 h (p = 0.36) or ≥15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Outcomes and Utilization of Kidneys from Deceased Donors with Acute Kidney Injury

Utilization and long‐term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr >2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [CI] 6.5–7.6) and 1.6–2.0 mg/dL (AOR 2.7; CI 2.5–2.9) relative to sCr ≤1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

A Comparison of Alemtuzumab with Basiliximab Induction in Simultaneous Pancreas–Kidney Transplantation

Alemtuzumab is a humanized, rat monoclonal antibody directed against the CD52 antigen. After binding, alemtuzumab causes profound and durable depletion and has been successfully used as immune induction therapy for organ transplantation.

Single Kidney Transplantation from Young Pediatric Donors in the United States

Kidney transplantation (KTX) from small pediatric donors is performed as single or en bloc. Criteria to determine when to split pediatric donor kidneys and transplant as singles are not well established. Data reported to the Scientific Registry of Transplant Recipient for donors <10 yrs from 1995 to 2007 were reviewed (n = 5079). Donors were categorized by weight group by 5 kg increments and solitary (n = 3503) versus en bloc (n = 1576). The primary outcome was overall graft survival. Results were compared as adjusted hazard ratios (aHR) relative to ideal standard criteria donors (SCDs) (defined as age 18–39 without other risk factors), non‐ideal SCDs (all other SCDs) and expanded criteria donors (age 50–59 with other risk factors or age ≥60). Single KTX from donors ≥ 35 kg conferred a similar risk of graft survival as ideal SCDs. Of donors 10–34 kg, risks of en bloc KTX were similar to ideal and risks of single KTX to non‐ideal SCDs; single and en bloc KTXs had 7.9 and 5.2 graft losses per 100 follow‐up years, respectively. Single KTX from donors >35 kg are similar to ideal SCDs. Single KTX from donors 10–35 kg are similar to non‐ideal SCDs. From a resource perspective, pediatric donors 10–35 kg used as singles offer more cumulative graft years than when used en bloc.

The Success of Continued Steroid Avoidance After Kidney Transplantation in the US

There has been a significant increase in the use of steroid avoidance regimens as initial treatment for kidney transplant recipients. Early results of the effectiveness of this strategy has been mixed with certain prospective trials indicating increased acute rejection but population‐based studies indicating similar or better graft survival as compared to steroid maintenance. We conducted a retrospective study of national registry data to evaluate risk factors for discontinuation of steroid avoidance protocols based on patient characteristics and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant recipients in the US with at least 6 months graft survival including 24 218 initially discharged without maintenance steroids. We utilized logistic models to assess risk factors for new initiation of steroids after initial steroid‐avoidance and survival models to describe graft survival for patients after return to steroids. The most prominent risk factors for new initiation of steroids after deceased donor kidney transplantation included African‐American race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR = 1.85, p < 0.01), elevated HLA‐MM (AOR = 1.26, p < 0.01) and older donor age (AOR = 1.19, p < 0.01). Concomitant medications were also significantly associated with the propensity to newly initiate steroids. Cumulatively the study suggests that both patient characteristics and concomitant medications are strongly associated with the success of steroid avoidance immunosuppressive regimens.

Combined Resection of the Liver and Pancreas for Malignancy

BACKGROUND Combined resection of both the liver and pancreas for malignancy remains a controversial procedure. To many, the need for such an extended procedure implies an extent of disease that is usually not amenable to surgical control, and the extent of the procedure exposes the patients to substantial operative risks. The purpose of this study was to assess our results with combined resection of the liver and pancreas. STUDY DESIGN Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included 26 pancreaticoduodenectomies (PD) and 14 distal pancreatic resections. Liver resections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. RESULTS There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy. Mean hospital stay was 14 days (range 7 to 42 days). Median follow-up was 30 months (range 3 to 76 months). Patients undergoing resection for neuroendocrine tumors had a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p = 0.01). CONCLUSIONS Combined resection of the liver and pancreas can be performed safely. The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindication to resection in selected patients.

Import Kidney Transplants from Nonmandatory Share Deceased Donors: Characteristics, Distribution and Outcomes

Outcomes of locally rejected kidneys transplanted at other centers (import KTX) are unknown. SRTR data from 2000 to 2009 of deceased‐donor KTXs excluding 0‐mismatch, paybacks, and other mandatory shares were compared by location of KTX at local (n = 48 165), regional (n = 4428) or national (n = 4104) centers using multivariable regression models. Compared to nonmandatory share local transplants, import KTX were associated with significantly higher overall risks of patient death (regional aHR 1.15, p < 0.01; national aHR 1.14, p < 0.01), and graft failure (regional aHR 1.17, p < 0.01; national aHR1.21, p < 0.01). In paired analysis, the risk of delayed graft function (DGF) for import KTX was higher compared to locally transplanted mates (regional aOR 1.53, p < 0.01, national aOR 2.14, p < 0.01); however, despite longer ischemia times, overall graft survival was similar. Mean cold ischemia times (CIT) pre‐ and post‐DonorNet® were similar for local and regional transplants, but significantly higher for national transplants (28.9 ± 9.9 vs. 29.9 ± 9.7 h, respectively, p = 0.01). Import KTX is associated with increased risks of graft failure, patient death and DGF. In the era of DonorNet® cold ischemia times of kidneys imported to regional centers are not improved compared to pre‐DonorNet®; and, those of national centers are significantly prolonged.