Allograft Procurement Research Articles

Intraoperative Anesthetic Strategies to Mitigate Early Allograft Dysfunction After Orthotopic Liver Transplantation: A Narrative Review.

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment.

In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.

Renal allograft procurement from living unrelated donors in Iran: What falls under the eclipse.

Renal transplantation is the treatment of choice for end stage kidney disease. However, despite all the efforts to expand the donor pool, the shortage of donors is increasing and as a consequence, there has been a significant increase in the number of patients on transplant waiting lists globally. Societies worldwide have employed different methods to address this, each with specific ethical concerns surrounding them. Over three decades ago, a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature. Nevertheless, despite all these extensive discussions and publications, several key aspects of the program have still not been properly elucidated and addressed. In this article, the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.

Maximizing Solid Organ and Face Transplant Procurement Team Coordination: The Posterior Tibial Artery Flap as an Ideal Sentinel Flap

Face transplantation became a reality with the first case performed in 2005. Facial tissue allograft procurement is technically complex and time-intensive. Brain-dead deceased donors are frequently, if not always, multiorgan donors. Every effort should be made during face allograft recovery to minimize any risk to the recovery of lifesaving solid organs. Some programs require the procurement of a myofascial vascularized skin graft to function as a sentinel flap allowing frequent monitoring for rejection without negatively impacting the esthetics of the face graft. Up till now, the flap used has been the radial forearm flap. Procuring the radial forearm flap places the procuring team in close proximity to the head and torso, where the face recovery and the solid organ recovery teams would require unhindered access. Here, we present the posterior tibial artery flap as an alternative flap that would provide benefits to the coordination of the multiple teams working to procure organs from a deceased donor.

Revitalizing pancreas transplantation: creation of a hands-on training course for pancreas allograft procurement, backbench preparation, and transplantation.

Despite a steady increase in the number of organs available for transplant in the United States, over the last two decades there has been a precipitous decrease in the annual number of pancreas transplants performed. One overlooked consequence of this decline in pancreas transplant volume has been a decrease in experience in proper pancreas procurement and transplantation techniques for transplant surgeons as well as fewer trained abdominal transplant fellows entering the workforce certified for pancreas procurement and transplantation, with those achieving certification having less-developed judgment, skills, and experience. To augment current fellowship training and provide a concentrated experience in pancreas procurement and transplantation, the ASTS developed a hands-on surgical skills workshop focused on proper techniques for pancreas allograft procurement and backbench preparation.

Donor-recipient matching in hand transplantation: a comparison of anthropometric measurements, 3-dimensional virtual models and printed epitheses.

Donor-recipient matching in hand transplantation remains challenging. The usefulness of three-dimensional (3-D) virtual models and printed epitheses were compared with measurements on cadaveric extremities to evaluate the most accurate method of donor-recipient matching for allograft procurement. Ten anthropometric measurements were recorded from 12 human cadaveric upper extremities and matched to printed epitheses and 3-D virtual models. Five circumferential and two longitudinal measurements obtained an intra-class correlation of >0.75 with all three methods, with the Kaplan (0.973) and wrist circumferences (0.942) achieving the highest concordance. Measurement on cadaveric specimens was the most reliable method. Using different combinations of donor hand and recipient forearms, a series of 72 virtual transplantations were then created, and their compatibility rated by ten transplant surgeons. The results confirmed that anthropometric measurements, obtained directly from potential human donor limbs and based on wrist circumference as the primary parameter, provide the best and most clinically relevant donor-recipient match.

Current vascular allograft procurement, cryopreservation and transplantation techniques in the Asan Medical Center Tissue Bank

Current vascular allograft procurement, cryopreservation and transplantation techniques in the Asan Medical Center Tissue Bank

Facial Transplantation: Principles and Evolving Concepts.

After studying this article, the participant should be able to: 1. Appreciate the evolution and increasing complexity of transplanted facial allografts over the past two decades. 2. Discuss indications and contraindications for facial transplantation, and donor and recipient selection criteria and considerations. 3. Discuss logistical, immunologic, and cost considerations in facial transplantation, in addition to emerging technologies used. 4. Understand surgical approaches and anatomical and technical nuances of the procedure. 5. Describe aesthetic, functional, and psychosocial outcomes of facial transplantation reported to date. This CME article highlights principles and evolving concepts in facial transplantation. The field has witnessed significant advances over the past two decades, with more than 40 face transplants reported to date. The procedure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous reconstructive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date.

Anesthetic Considerations in Facial Transplantation: Experience at NYU Langone Health and Systematic Review.

Background:Anesthetic considerations are integral to the success of facial transplantation (FT), yet limited evidence exists to guide quality improvement. This study presents an institutional anesthesia protocol, defines reported anesthetic considerations, and provides a comprehensive update to inform future directions of the field.Methods:An institutional “FT Anesthesia Protocol” was developed and applied to 2 face transplants. A systematic review of 3 databases captured FTs in the peer-reviewed literature up to February 2020. Two reviewers independently screened titles and abstracts to include all clinical articles with FT recipient and/or donor-specific preoperative, intraoperative, and relevant postoperative anesthetic variables. Data charting guided a narrative synthesis, and quantitative synthesis reported variables as median (range).Results:Our institutional experience emphasizes the importance of on-site rehearsals, anticipation of patient-specific anesthetic and resuscitative requirements, and long-term pain management. Systematic search identified 1092 unique records, and 129 met inclusion criteria. Reports of 37 FTs in the literature informed the following anesthetic axes: donor pre- and intraoperative management during facial allograft procurement, recipient perioperative care, immunotherapy, antimicrobial prophylaxis, and pain management. Quantitative synthesis of 30 articles showed a median operative time of 18 hours (range, 9–28) and fluid replacement with 13 L (5–18) of crystalloids, 13 units (0–66) of packed red blood cells, 10 units (0–63) of fresh frozen plasma, and 1 unit (0–9) of platelets.Conclusions:Anesthetic considerations in FT span the continuum of care. Future efforts should guide standard reporting to establish evidence-based strategies that promote quality improvement and patient safety.

Technique for Rapid Hand Transplant Donor Procurement Through the Elbow.

Background: Hand and distal forearm allotransplantation has advanced over the last 20 years from experimental to a viable treatment option for bilateral upper extremity amputation. Despite widespread growth of this field, there are few technical reports that elaborate the details of donor arm procurement. This article details a technique for rapid donor procurement through the elbow for mid to distal forearm-level hand allograft procurement. Methods: Nine arm procurements were performed on deceased tissue-only donors provided by the local organ procurement organization, including two bilateral and five unilateral cases. Technique highlights include using a fishmouth incision through the lateral and medical epicondyles, identification of the neurovascular structures, and disarticulating the elbow joint. Results: Procuring through the elbow provides straightforward anatomy, bypasses the need to cut through bone, and allows tissue allotransplantation teams to achieve procurement, flushing, and packaging within 20 minutes. Conclusions: Procurement through the elbow is a simple procedure that streamlines the process for multi-organ donors by minimizing the time needed for hand allograft procurement. Team coordination and surgical rehearsals are essential for successful hand and upper extremity procurement and allotransplantation.

P2A.05: Technique of Deceased Donor Vascularized Abdominal Wall Allograft Procurement

P2A.05: Technique of Deceased Donor Vascularized Abdominal Wall Allograft Procurement

Three-Dimensional Analysis of Donor Masks for Facial Transplantation.

Face transplant teams have an ethical responsibility to restore the donor's likeness after allograft procurement. This has been achieved with masks constructed from facial impressions and three-dimensional printing. The authors compare the accuracy of conventional impression and three-dimensional printing technology. For three subjects, a three-dimensionally-printed mask was created using advanced three-dimensional imaging and PolyJet technology. Three silicone masks were made using an impression technique; a mold requiring direct contact with each subject's face was reinforced by plaster bands and filled with silicone. Digital models of the face and both masks of each subject were acquired with Vectra H1 Imaging or Artec scanners. Each digital mask model was overlaid onto its corresponding digital face model using a seven-landmark coregistration; part comparison was performed. The absolute deviation between each digital mask and digital face model was compared with the Mann-Whitney U test. The absolute deviation (in millimeters) of each digitally printed mask model relative to the digital face model was significantly smaller than that of the digital silicone mask model (subject 1, 0.61 versus 1.29, p < 0.001; subject 2, 2.59 versus 2.87, p < 0.001; subject 3, 1.77 versus 4.20, p < 0.001). Mean cost and production times were $720 and 40.2 hours for three-dimensionally printed masks, and $735 and 11 hours for silicone masks. Surface analysis shows that three-dimensionally-printed masks offer greater surface accuracy than silicone masks. Greater donor resemblance without additional risk to the allograft may make three-dimensionally-printed masks the superior choice for face transplant teams. Therapeutic, V.

Allograft for knee ligament surgery: an American perspective.

Allografts are frequently use for ligamentous reconstruction at the knee. In the United States, tissue donation and distribution are highly regulated processes with thorough oversight from private and government entities. Allograft is widely available in the United States and allograft procurement is a large industry with varying procurement, sterilization, processing, and distribution procedures. It is important to understand allograft regulation and processing which may affect graft mechanical properties and biological graft integration. English-language literature, United States government and regulatory agency statues pertaining to allograft procurement, distribution, and usage were reviewed and the findings summarized. During the processing of allograft, multiple factors including sterilization procedures, irradiation, storage conditions, and graft type all affect the biomechanical properties of the allograft tissue. Biological incorporation and ligamentization of allograft does occur, but at a slower rate compared with autograft. For ligamentous reconstruction around the knee, allograft offers shorter operative time, no donor-site morbidity, but has shown an increased risk for graft failure compared to autograft. This article reviews the regulations on graft tissue within the United States, factors affecting the biomechanics of allograft tissue, differences in allograft tissue choices, and the use of allograft for anterior cruciate ligament reconstruction and multiligamentous knee injury reconstruction. V.

Bacterial contamination rate and associated factors during bone and tendon allograft procurement from Spanish donors: exploring the contamination patterns

Allograft contamination during extraction represents a major limiting factor for tissue bank availability. Contamination rates remain persistently high independent of the hospital, country or year considered. To analyse the factors associated with contamination of bone and tendon samples extracted from Spanish donors. Data for 1162 bone and tendon samples extracted from 102 donors between 2014 and 2017 were collected retrospectively from the hospital database. Descriptive statistics, potentially associated factors and correlation of contamination between samples extracted from different anatomical locations of the same donor were analysed. In total, 227 (19.54%) of the extracted samples [131 (18.49%) bone samples and 96 (20.92%) tendon samples] rendered positive cultures and were discarded. Male sex [odds ratio (OR) 2.023; P=0.019], extraction of >10 samples per donor (OR 1.997; P<0.001) and extraction time >240 min (OR 1.755; P=0.001) were factors independently associated with a higher contamination rate. Meanwhile, the tissue sample type 'bone-patellar tendon-bone' was associated with a significantly lower contamination rate (OR 0.446; P=0.001). Significant correlation between certain localization of contaminated samples and the concordance of bacterial species was also observed. Factors related to the extraction procedure, such as total extraction time, extraction sequence, number of samples extracted and anatomical location of extracted samples, play a major role in allograft contamination. Further optimization of procedures, guided by the contamination patterns analysed in this study, should help to increase tissue bank availability.

Liver Perfusate Natural Killer Cells From Deceased Brain Donors and Association With Acute Cellular Rejection After Liver Transplantation: A Time-to-Rejection Analysis.

The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes. Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular rejections (ACRs) in 46 adult recipients who underwent LT between 2010 and 2014 at our institute. Cox regression models were used to study relevant risk factors in order to estimate hazard ratios for episodes of rejection after LT. Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NK T cellular subset (P = 0.001). The length of follow-up after LT was 41.0 ± 20.9 months, and 11 (23.9%) recipients experienced biopsy-proven ACR. At time-to-rejection proportional regression analysis, a cutoff value of 33.7% was optimal, with a sensitivity of 1, specificity of 0.57, and positive and negative predictive values of 0.42 and 1, respectively. The liver perfusate NK cell subset was strongly associated with biopsy-proven ACR (hazard ratio, 10.7; P = 0.02). Liver perfusate cytofluorimetric phenotyping may contribute as a targeted preoperative tool to predict the risk of ACR, and as clinical test in translational studies that aim to improve donor allograft procurement and transplant outcomes.

Current vascular allograft procurement, cryopreservation and transplantation techniques in the Czech Republic

Vascular allotransplantations are performed worldwide in selected patients suffering from vascular prosthesis infection or critical limb ischemia. Either fresh or cryopreserved vascular allograft may be used. In various points, we address several aspects (allograft procurement, cryopreservation and transplantation technique) of the program of vascular allotransplantations in the Czech Republic. Vascular grafts retrieval has been done within multiorgan harvests using no-touch technique. Very short time of cold ischemia is achieved due to close cooperation with Tissue Establishment where the following processing of cryopreservation is performed. Meeting all necessary quality criteria is a prerequisity for releasing grafts for clinical application. Standardized thawing protocol and surgical handling aims to minimize microfractures before implantation. Based on experimental and clinical work, the first validation of cryopreserved arterial and venous grafts for clinical use was performed between 2011 and 2013 in the Czech Republic. The developement of storage of vascular tissue in banks was stimulated in 2000-2010 by the issue of EU directives and national harmonized norms, aimed at assurance of high quality and safety of cells and tissues used for transplantations in humans. There are several crucial moments affecting final quality, including graft retrieval within a multiorgan harvest, short ischemic time, cryopreservation and thawing technique used. The recommended surgical handling during implantation may also affect results and graft-related complications.

Vascularized composite allotransplantation in the United States: A descriptive analysis of the Organ Procurement and Transplantation Network Data.

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.

Abstract: Full Facial Allotransplantation Including the Temporomandibular Joints: An Anatomical Study and Surgical Protocol

INTRODUCTION: Face allotransplantation cardinally shifted the reconstruction paradigm of unmanageable facial defects. Incorporation of temporomandibular joint (TMJ) in total face allotransplant can further improve functional outcome in these patients. The purpose of our study was to evaluate the vascular supply of TMJ and develop a surgical protocol of a total face allotransplantation including TMJ. METHODS: 100 skulls and mandibles from the Hamann-Todd collection (Cleveland Museum of Natural History) and 100 facial CT scans were examined to evaluate the variability of TMJ dimensions. Intercondylar distance, width, length and height of condyles, mandibular ramus and body dimensions, condylar fossa breadth and anteroposterior dimension, and gonial (GA), intercondylar (ICA) and condyle-symphysis (CSA) angles were measured on dry skulls. Bilateral frontal ramal inclination (FRI) and lateral ramal inclination (LRI) were measured in 3D reconstructed CT scans. Injection of the common carotid arteries with red-colored latex was performed in eight fresh cadaver heads. They were then dissected for visualization of the vascular branches entering the TMJ. Four fresh cadavers were then used to perform a TMJ-included total face transplantation. Donor allografts were harvested using an extracranial Le Fort III approach combined with a temporal craniotomy to include the total TMJ. Internal carotid and middle meningeal arteries were well preserved. Bilateral sagittal split osteotomy was performed to address any anticipated discrepancy between donor and recipient intercondylar distance. The allograft was transferred to the recipient face and secured with miniplates at the orbital rims and nasal bridge. TMJs were secured on the zygomatic processes of temporal bones by long miniscrews. RESULTS: Statistically significant difference between genders were observed in all parameters measured on dry skulls except for ICA and CSA. There was a statistically significant difference of FRI between genders in CT measurements. The mean values, standard deviation and the range of all measurement are provided bellow in male vs female format. Intercondylar distance: 118.1mm±5 (range 104.6-128mm) vs 112.2mm±6.5 (range 98–123.3mm) p<0.05 Gonion-gonion distance: 99.0mm±6.3 (range 86.6–115.3mm) vs 91.2mm±4.9 (range 82.7–104.5mm) p<0.05 Lateral fossa-lateral fossa points: 120.1mm±4.6 (range 109.5–129.1mm) vs 113.3mm±4.9 (range 101.7–123.2mm) p<0.05 ICA: 141.1° ±10.2 (range 118.9–162.5°) vs 139.7°±10.0 (range 119.3–160.3°), p>0.05 CSA: 64.8°±5.6 (range 53.4–74.6°) vs 64.1°±5.6 (range 54–77.1°), p>0.05 GA: 122.4°±7.8 (range 104.2–147.9°) vs 126.4°±6.2 (range 114.2–144.6°), p<0.05 FRI: 79.3°±4.1 (range 69.7–90.2°) vs 77.1°±3.6 (range 71.3–96.9°), p<0.05 LRI: 82.1°±5.4 (range 69.2–96.8°) vs 82.3°±5.8 (range 114.2–144.6°), p>0.05 The TMJ received 1 – 3 direct branches (maximal diameter 0.7–0.8 mm) from the maxillary and middle meningeal arteries medially, and the superficial temporal artery laterally. Fixation of TMJ on zygomatic processes minimally increased the intercondylar distance on recipient face. However, transplanted joints were located more inferior and anterior compared to their normal anatomical position. Class 1 original donor occlusion was achieved with normal ramal inclination and mandibular range of motion. CONCLUSION: We demonstrated that TMJ-included total face allograft procurement and transplantation is technically and functionally feasible and reasonable occlusion, range of motion and lateral excursions is achievable.

Anti-Inflammatory Effect of Atorvastatin on the Kidney Graft of Living Donor Transplants.

BackgroundRecent studies have demonstrated that statins have anti-inflammatory and immunomodulatory properties, which could be considered beneficial in kidney transplantations. This study assesses the anti-inflammatory effect of atorvastatin on the kidney grafts of living donor transplants.Material/MethodsIn a randomized clinical trial, kidney donors were divided into 2 groups. The study group constituted 24 donors who received 40 mg atorvastatin, and 24 donors who received a placebo control, 4 weeks prior to transplantation. Serum C-reactive protein (CRP) levels were measured before and after atorvastatin administration. CRP and renal function of kidney recipients were measured at baseline and 1, 6, and 24 hours after transplantation.ResultsAfter 4 weeks of treatment, the CRP level was 5.62±3.82 mg/dL in the control group and 3.27±0.62 mg/dL in the study group (P=0.007). Upon reperfusion, CRP levels in recipients at 1 hour were, 5.8±3.9 and 3.8±1.0 mg/dL, respectively (P=0.04). Twenty-four hours after the kidney transplantations, serum creatinine levels were 2.5±1.5 mg/dL in the study group and 3.7±2.4 mg/dL in the control group (P=0.04).ConclusionsOur study suggests that the use of atorvastatin prior to allograft procurement of kidney transplant, reduces the acute kidney inflammatory burden profile, and promotes an improved kidney function recovery following transplantation.

Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft Injury

Background Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury.Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n=13), after implantation and reperfusion (postischemia; n=13), and at 3 or 12 months after transplant (n=5 each); a cross-sectional cohort with preimplantation biopsy specimens (n=82); and a cross-sectional cohort with postreperfusion biopsy specimens (n=46).Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables.Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.