hEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.

INTRODUCTION: Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti-pig antibody binding (α-1,3-galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO-1]), and a self-recognition receptor (integrin-associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena. METHODS: Livers from GaltKO.hCD46 pigs ("2-gene," n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO-1 ("6-gene," n = 4) were perfused ex vivo with whole human blood. Six-gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively. RESULTS: The average perfusion times increased from 304 (±148) min in the 2-gene group to 856 (±61) min in the 6-gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2-gene to 1354 U/h in the 6-gene group (p = .047). Platelet sequestration tended to be delayed in the 6-gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6-gene group (p = .058). CONCLUSIONS: The combination of the hEPCR.hTBM.hCD47.hHO-1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.

Extracorporeal membrane oxygenation support following liver transplantation-A case series.

BACKGROUND: Postoperative severe cardiopulmonary failure carries a high rate of mortality. Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy when conventional therapies fail. METHODS: We retrospectively reviewed our experience with ECMO support in the early postoperative period after liver transplant between September 2011 and May 2016. RESULTS: Out of 537 liver transplants performed at our institution, seven patients required ECMO support with a median age of 52 and a median MELD score of 28. Veno-venous ECMO was used in four patients with severe respiratory failure while the rest required veno-arterial ECMO for circulatory failure. The median time from transplant to cannulation was 3 days with a median duration of ECMO support of 7 days. All patients except one were successfully decannulated. The median hospital length of stay was 58 days with an in-hospital mortality of 28.6%. CONCLUSION: Extracorporeal membrane oxygenation can be considered a viable rescue therapy in the setting of severe postoperative cardiopulmonary failure. Extracorporeal membrane oxygenation therapy was successful in saving patients who were otherwise unsalvageable.

Synthetic liver function is detectable in transgenic porcine livers perfused with human blood.

In addition to immune barriers, molecular incompatibilities between species are predicted to limit pig liver survival in primate xenotransplantation models. Assessment and measurement of synthetic function of genetically modified porcine livers after ex vivo perfusion with human blood have not previously been described. Eight porcine livers from α1,3-galactosyl transferase knockout and human membrane cofactor (GalTKO.hCD46), six livers from GalTKO.hCD46 and N-glycolylneuraminic acid knockout (GalTKO.hCD46.Neu5GcKO), and six livers from GalTKO.hCD46 with humanized decay-accelerating factor (hCD55), endothelial protein C receptor (hEPCR), tissue factor pathway inhibitor (hTFPI), and integrin-associated protein (hCD47) (GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47) pigs were perfused with human blood under physiologic conditions. Timed blood samples were tested for liver enzymes and for pig-specific albumin production via Western blot. Porcine albumin levels increased with time in all experiments. By densitometry, GalTKO.hCD46.Neu5GcKO livers had the highest albumin levels, measured both as total produced, and when controlled for perfusion duration, compared to GalTKO.hCD46 (P = .068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47 livers (P = .04). Porcine livers perfused with human blood demonstrated the synthetic ability to produce albumin in all cases. GalTKO.hCD46.Neu5GcKO pig livers demonstrated the most robust albumin production. This suggests that the Neu5GcKO phenotype provides a protective effect on the graft due to decreased human antibody recognition and graft injury.

Robotic-assisted single-port donor nephrectomy using the da Vinci single-site platform.

BACKGROUND: Although single-port donor nephrectomy offers improved cosmetic outcomes, technical challenges have limited its application to selected centers. Our center has performed over 400 single-port donor nephrectomies. The da Vinci single-site robotic platform was utilized in an effort to overcome the steric, visualization, ergonomic, and other technical limitations associated with the single-port approach. MATERIALS AND METHODS: Food and Drug Administration device exemption was obtained. Selection criteria for kidney donation included body mass index <35, left kidney donors, and ≤2 renal arteries. After colonic mobilization using standard single-port techniques, the robotic approach was utilized for ureteral complex and hilar dissection. RESULTS: Three cases were performed using the robotic single-site platform. Average total operative time was 262 ±â€¯42 min including 82 ±â€¯16 min of robotic use. Docking time took 20 ±â€¯10 min. Blood loss averaged 77 ±â€¯64 mL. No intraoperative complications occurred, and all procedures were completed with our standard laparoscopic single-port approach. CONCLUSIONS: This is the first clinical experience of robotic-assisted donor nephrectomy utilizing the da Vinci single-site platform. Our experience supported the safety of this approach but found that the technology added cost and complexity without tangible benefit. Development of articulating instruments, energy, and stapling devices will be necessary for increased application of robotic single-site surgery for donor nephrectomy.

Minimally invasive donor nephrectomy: current state of the art.

BACKGROUND: The concept of a minimally invasive live donor nephrectomy developed over 20 years ago. Surgeons gained expertise with the laparoscopic technique and utilized multiple variations that are now utilized in transplant centers throughout the world. Recent modifications include laparoendoscopic single-site and robotic approaches that have been adopted by an additional smaller set of programs. PURPOSE: Review was performed of the following eight different surgical approaches to a "minimally invasive" live donor nephrectomy: laparoscopic (LDN), hand-assisted laparoscopic (HALDN), retroperitoneoscopic (RLDN), hand-assisted retroperitoneoscopic (HARS), single-port laparoscopic (LESS), robotic-assisted laparoscopic (RALDN), mini open, and natural orifice transluminal endoscopic (NOTES). The techniques are described and summaries of available outcomes and complications are presented. CONCLUSIONS: Traditional surgical techniques of open donor nephrectomy have transitioned to minimally invasive techniques. With adoption of these techniques as the preferred approach, several variations have and continue to evolve. The current minimally invasive donor nephrectomy techniques share low complication rates and excellent outcomes.

Advances in liver xenotransplantation.

PURPOSE OF REVIEW: This review highlights advances in liver xenotransplantation, focusing on immunologic barriers and mechanisms underlying graft failure and recipient demise, and discussion of recent in-vivo results. RECENT FINDINGS: Pig to primate models of liver xenotransplantation have been plagued by thrombocytopenia, anemia, and coagulopathy. It is now known that platelet sequestration is mediated by liver sinusoidal endothelial cells and Kupffer cells in part by asialoglycoprotein receptor 1-driven mechanisms. Xenoantigens, specifically N-glycolylneuraminic acid, play a role in graft injury as well as red blood cell consumption. Finally incompatibilities between coagulation cascade molecules contribute to lethal coagulopathy, but can be counteracted with genetic modifications and coagulation factor supplementation. Survival has markedly increased with this strategy. SUMMARY: An increased understanding of the cellular mechanisms responsible for failure of in-vivo pig to primate liver xenotransplant models has led to improved outcomes, and this recent success supports initial clinical application.

N-glycolylneuraminic acid knockout reduces erythrocyte sequestration and thromboxane elaboration in an ex vivo pig-to-human xenoperfusion model.

BACKGROUND: Wild-type pigs express several carbohydrate moieties on their cell surfaces that differ from those expressed by humans. This difference in profile leads to pig tissue cell recognition of human blood cells causing sequestration, in addition to antibody-mediated xenograft injury. One such carbohydrate is N-glycolylneuraminic acid (Neu5Gc), a sialic acid molecule synthesized in pigs but not in humans. Here, we evaluate livers with and without Neu5Gc in an ex vivo liver xeno perfusion model. METHODS: Livers from pigs with an α1,3-galactosyl transferase gene knockout (GalTKO) and transgenic for human membrane cofactor (hCD46) with (n = 5) or without (n = 7) an additional Neu5Gc gene knock out (Neu5GcKO) were perfused ex vivo with heparinized whole human blood. A drug regimen consisting of a histamine inhibitor, thromboxane synthase inhibitor, and a murine anti-human GPIb-blocking antibody fragment was given to half of the experiments in each group. RESULTS: Liver function tests (AST and ALT) were not significantly different between livers with and without the Neu5GcKO. GalTKO.hCD46.Neu5GcKO livers had less erythrocyte sequestration as evidenced by a higher mean hematocrit over time compared to GalTKO.hCD46 livers (P = .0003). The addition of Neu5GcKO did not ameliorate profound thrombocytopenia seen within the first 15 minutes of perfusion. TXB2 was significantly less with the added drug regimen (P = .006) or the presence of Neu5GcKO (P = .017). CONCLUSIONS: The lack of Neu5Gc expression attenuated erythrocyte loss but did not prevent profound early onset thrombocytopenia or platelet activation, although TXB2 levels were decreased in the presence of Neu5GcKO.

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

INTRODUCTION: Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. METHODS: Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. RESULTS: The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. CONCLUSIONS: High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets.

Surgical complications of laparoendoscopic single-site donor nephrectomy: a retrospective study.

The single-port approach has been associated with an unacceptably high rate of umbilical port hernias in large series of patients undergoing single-port cholecystectomy and colectomy and with additional surgical risks thought secondary to technical and ergonomic limitations. A retrospective review of 378 consecutive laparoendoscopic single-site(LESS) donor nephrectomies performed between 04/15/2009 and 04/09/2014 was conducted. Twelve patients (3%) developed an umbilical hernia. Eleven (92%) were female and eight (73%) of these patients had a prior pregnancy. Hernias were reported 13.5 ± 6.9 months after donation, and the mean size was 5.1 ± 3.7 cm. Seven additional cases (1.9%) required a return to the operating room for internal hernia (2), evisceration (1), bleeding (1), enterotomy (1), and wound infection (2). The original incision was utilized for reexploration. One patient required emergent conversion to an open procedure for bleeding during the initial donation. There were no mortalities. Recipient patient and graft survival were 99% and 99% at 1 year, respectively. Although reports associated with earlier experiences with single-site procedures suggested an unacceptably high rate of hernias at the surgical site, this does not seem to be the case at our center. This technique is a reliable surgical technique for left donor nephrectomy at this institution.

Sequential kidney-liver transplantation from the same living donor for lecithin cholesterol acyl transferase deficiency.

BACKGROUND: Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease (ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency. METHODS: A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). One year following the kidney transplant, auxiliary partial orthotopic liver transplant (APOLT) of a left lateral segment from the same donor was performed. RESULTS: At 5 years follow-up, there have been no major complications, readmissions, or rejection episodes. Serum lipid abnormalities recurred within the first year, but liver and kidney allograft function remains intact. CONCLUSION: Few cases of sequential transplantation from the same LD have been performed in adults. This is the first APOLT and multi-organ transplant performed for LCAT deficiency. Sequential organ transplant from the same LD for ESRD secondary to a metabolic disorder of the liver is feasible in adults and should be further investigated.

Pig-to-baboon liver xenoperfusion utilizing GalTKO.hCD46 pigs and glycoprotein Ib blockade.

BACKGROUND: Although transplantation of genetically modified porcine livers into baboons has yielded recipient survival for up to 7 days, survival is limited by profound thrombocytopenia, which becomes manifest almost immediately after revascularization, and by subsequent coagulopathy. Porcine von Willebrand's factor (VWF), a glycoprotein that adheres to activated platelets to initiate thrombus formation, has been shown to constitutively activate human platelets via their glycoprotein Ib (GPIb) receptors. Here, we report our pig-to-primate liver xenoperfusion model and evaluate whether targeting the GPIb-VWF axis prevents platelet sequestration. METHODS: Twelve baboons underwent cross-circulation with the following extracorporeal livers: one allogeneic control with a baboon liver, 4 xenogeneic controls with a GalTKO.hCD46 pig liver, 3 GalTKO.hCD46 pig livers in recipients treated with αGPIb antibody during perfusion, and 4 GalTKO.hCD46 pig livers pre-treated with D-arginine vasopressin (DDAVP) in recipients treated with αGPIb antibody during perfusion. RESULTS: All perfused livers appeared grossly and macroscopically normal and produced bile. Xenograft liver perfusion experiments treated with αGPIb antibody may show less platelet sequestration during the initial 2 h of perfusion. Portal venous resistance remained constant in all perfusion experiments. Platelet activation studies demonstrated platelet activation in all xenoperfusions, but not in the allogeneic perfusion. CONCLUSION: These observations suggest that primate platelet sequestration by porcine liver and the associated thrombocytopenia are multifactorial and perhaps partially mediated by a constitutive interaction between porcine VWF and the primate GPIb receptor. Control of platelet sequestration and consumptive coagulopathy in liver xenotransplantation will likely require a multifaceted approach in our clinically relevant perfusion model.

Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up.

INTRODUCTION: The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18% to 28% at 10 yr after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival. METHODS: We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 yr. RESULTS: Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival >1 yr developed end-stage renal disease (ESRD) at five, 10, and 20 yr, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one yr, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin inhibitor-based regimen. CONCLUSION: Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen.

The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes.

Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists' roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4-6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Complications associated with liver transplantation in the obese recipient.

The prevalence of the metabolic syndrome with attendant morbid obesity continues to increase nationwide. A concomitant increase in non-alcoholic steatohepatitis (NASH) and associated end-stage liver disease requiring transplantation is expected to parallel this trend. Between January 1, 1997 and December 31, 2008, our center performed 813 solitary adult deceased-donor liver transplants. Patients were divided into groups based on the World Health Organization International Classification of obesity. Patients within each obesity class were compared to normal weight recipients. Preoperative demographics among all groups were similar. NASH was more common in higher BMI groups. Operative time, blood product usage, ICU length of stay, infectious complications, and biliary complications requiring intervention were all higher in obese recipients. Deep venous thrombosis occurred more commonly in patients with Class III obesity. Patients with Class II obesity had lower patient (HR 1.82, CI 1.09-3.01, p=0.02) and allograft survival (HR 1.62, CI 1.02-2.65, p=0.04). Obesity class did not reach statistical significance on multivariate analysis. Despite increased technical operative challenges and medical complexities associated with increasing recipient BMI, morbid obesity in and of itself should not be an absolute contraindication to liver transplantation as these patients have reasonable long-term outcomes.

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients.

INTRODUCTION: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). METHODS: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. RESULTS: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. CONCLUSIONS: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

Alemtuzumab as compared to alternative contemporary induction regimens.

Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001). The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%, and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival was equivalent. Alemtuzumab was an independent risk factor for living donor allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01), CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The significantly worse graft survival in the alemtuzumab cohort may be due to the increased rates of AMR and infectious complications.

Ischemic Cholangiopathy Postdonation After Circulatory Death Liver Transplantation: Donor Hepatectomy Time Matters.

BACKGROUND: Outcomes of liver transplantation (LT) from donation after circulatory death (DCD) have been improving; however, ischemic cholangiopathy (IC) continues to be a problem. In 2014, measures to minimize donor hepatectomy time (DHT) and cold ischemic time (CIT) have been adopted to improve DCD LT outcomes. METHODS: Retrospective review of all patients who underwent DCD LT between 2005 and 2017 was performed. We compared outcomes of patients who were transplanted before 2014 (historic group) with those who were transplanted between 2014 and 2017 (modern group). RESULTS: We identified 112 patients; 44 were in the historic group and 68 in the modern group. Donors in the historic group were younger (26.5 versus 33, P = 0.007) and had a lower body mass index (26.2 versus 28.2, P = 0.007). DHT (min) and CIT (h) were significantly longer in the historic group (21.5 versus 14, P < 0.001 and 5.3 versus 4.2, P < 0.001, respectively). Fourteen patients (12.5%) developed IC, with a significantly higher incidence in the historic group (23.3% versus 6.1%, P = 0.02). There was no difference in graft and patient survival between both groups. CONCLUSION: In appropriately selected recipients, minimization of DHT and CIT may decrease the incidence of IC. These changes can potentially expand the DCD donor pool.