Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC).

Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.

Effect of donor nephrectomy time during circulatory-dead donor kidney retrieval on transplant graft failure.

BACKGROUND: When the blood supply ceases in a deceased organ donor, ischaemic injury starts. Kidneys are cooled to reduce cellular metabolism and minimize ischaemic injury. This cooling is slow and kidneys are lukewarm during nephrectomy. Smaller single-centre studies have shown that prolonged donor nephrectomy time decreases early kidney transplant function, but the effect on long-term outcome has never been investigated in large multicentre cohort studies. METHODS: The relationship between donor nephrectomy time and death-censored graft survival was evaluated in recipients of single adult-to-adult, first-time deceased-donor kidneys transplanted in the Eurotransplant region between 2004 and 2013. RESULTS: A total of 13 914 recipients were included. Median donor nephrectomy time was 51 (i.q.r. 39-65) min. Kidneys donated after circulatory death had longer nephrectomy times than those from brain-dead donors: median 57 (43-78) versus 50 (39-64) min respectively (P < 0·001). Donor nephrectomy time was independently associated with graft loss when kidneys were donated after circulatory death: adjusted hazard ratio (HR) 1·05 (95 per cent c.i. 1·01 to 1·09) per 10-min increase (P = 0·026). The magnitude of this effect was comparable to the effect of each hour of additional cold ischaemia: HR 1·04 (1·01 to 1·07) per h (P = 0·004). For kidneys donated after brain death, there was no effect of nephrectomy time on graft survival: adjusted HR 1·01 (0·98 to 1·04) per 10 min (P = 0·464). CONCLUSION: Prolonged donor nephrectomy time impairs graft outcome in kidneys donated after circulatory death. Keeping this short, together with efficient cooling during nephrectomy, might improve outcome.

ANTECEDENTES: La lesión por isquemia empieza en el momento que cesa la irrigación sanguínea del órgano donante. Para reducir el metabolismo celular y la lesión isquémica se reduce la temperatura de los riñones. Este enfriamiento es lento y los riñones se mantienen tibios durante la nefrectomía. Estudios unicéntricos con muestras pequeñas han demostrado que el tiempo de la nefrectomía del donante disminuye la función precoz del injerto renal, pero nunca se ha analizado su repercusión a largo plazo en grandes estudios multicéntricos. MÉTODOS: Se analizó la relación entre la duración de la nefrectomía del donante y la supervivencia del injerto en 13.914 adultos receptores de un primer riñón procedente de donante cadavérico adulto en la región de Eurotransplant entre los años 2004 y 2013. RESULTADOS: La mediana de duración de la nefrectomía del donante fue de 51 minutos (rango intercuartílico 39-65). En los riñones obtenidos en donantes a corazón parado la duración de la nefrectomía fue más prolongada que en los donantes en muerte cerebral (mediana 57 min (43-78 min) versus 50 min (39-64 min), P < 0,001). La duración de la nefrectomía en el donante se asoció de forma independiente con la pérdida del injerto (cociente de riesgos instantáneos, hazard ratio, HR, ajustado 1,05 por cada incremento de 10 minutos, i.c. del 95%: 1,01 a 1,09; P = 0,026) cuando los riñones se obtuvieron en donantes en parada cardíaca. La magnitud de este efecto fue comparable al efecto de cada hora adicional de isquemia fría (1,04, i.c. 95% 1,01-1,07, P = 0,004). En los riñones obtenidos de donantes en muerte cerebral, la duración de la nefrectomía no influyó en la supervivencia del injerto (HR ajustada 1,01 por aumento de 10 min, i.c. del 95%: 0,98 a 1,04). CONCLUSIÓN: La duración de la nefrectomía en donantes a corazón parado afecta la función de los injertos trasplantados. Reducir esta duración y disponer de un sistema de enfriamiento eficiente durante la nefrectomía podría mejorar los resultados.

Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review.

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation.

BACKGROUND: Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Preconditioning, reconditioning and postconditioning with argon and xenon protects against renal ischaemia-reperfusion injury in rodent models. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function in a porcine renal autotransplant model was tested. METHODS: Pigs (n = 6 per group) underwent left nephrectomy after 60 min of warm ischaemia (renal artery and vein clamping). The procured kidney was autotransplanted in a separate procedure after 18 h of cold storage, immediately after a right nephrectomy. Upon reperfusion, pigs were randomized to inhalation of control gas (70 per cent nitrogen and 30 per cent oxygen), argon (70 per cent and 30 per cent oxygen) or xenon (70 per cent and 30 per cent oxygen) for 2 h. The primary outcome parameter was peak plasma creatinine; secondary outcome parameters included further markers of graft function (creatinine course, urine output), graft injury (aspartate aminotransferase, heart-type fatty acid-binding protein, histology), apoptosis and autophagy (western blot, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining), inflammatory mediators and markers of cell survival/growth (mRNA and tissue protein quantification), and animal survival. Results are presented as median (i.q.r.). ANOVA and Kruskal-Wallis tests were used where indicated. RESULTS: Peak plasma creatinine levels were similar between the groups: control 20·8 (16·4-23·1) mg/dl, argon 21·4 (17·1-24·9) mg/dl and xenon 19·4 (17·5-21·0) mg/dl (P = 0·607). Xenon was associated with an increase in autophagy and proapoptotic markers. Creatinine course, urine output, injury markers, histology, survival and inflammatory mediators were not affected by the intervention. CONCLUSION: Postconditioning with argon or xenon did not improve kidney graft function in this experimental model. Surgical relevance Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Based on mainly small animal experiments, noble gases (argon and xenon) have been proposed to minimize this ischaemia-reperfusion injury and improve outcomes after transplantation. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function was tested in a porcine kidney autotransplantation model. The peak plasma creatinine concentration was similar in the control, argon and xenon groups. No other secondary outcome parameters, including animal survival, were affected by the intervention. Xenon was associated with an increase in autophagy and proapoptotic markers. Despite promising results in small animal models, postconditioning with argon or xenon in a translational model of kidney autotransplantation was not beneficial. Clinical trials would require better results.

The duration of asystolic ischemia determines the risk of graft failure after circulatory-dead donor kidney transplantation: A Eurotransplant cohort study.

Circulatory death donor (DCD) kidney transplantations are steadily increasing. Consensus reports recommend limiting donor warm ischemia time (DWIT) in DCD donation, although an independent effect on graft outcome has not been demonstrated. We investigated death-censored graft survival in 18 065 recipients of deceased-donor kidney transplants in the Eurotransplant region: 1059 DCD and 17 006 brain-dead donor (DBD) kidney recipients. DWIT was defined as time from circulatory arrest until cold flush. DCD donation was an independent risk factor for graft failure (adjusted hazard ratio [HR] 1.28, 95% CI 1.10-1.46), due to an increased risk of primary nonfunction (62/1059 vs 560/17 006; P < .0001). With DWIT in the model, DCD donation was no longer a risk factor, demonstrating that DWIT explains the inferior graft survival of DCD kidneys. Indeed, DCD transplants with short DWIT have graft survival comparable to that of standard-criteria DBD transplants (P = .59). DWIT also associated with graft failure in DCDs (adjusted HR 1.20 per 10-minute increase, 95% CI 1.03-1.42). At 5 years after transplantation, graft failure occurred in 14 of 133 recipients (10.5%) with DWIT <10 minutes, 139 of 555 recipients (25.0%) with DWIT between 10 and 19 minutes, and 117 of 371 recipients (31.5%) with DWIT ≥20 minutes. These findings support the expert opinion-based guidelines to limit DWIT.

The Impact of Anastomosis Time During Kidney Transplantation on Graft Loss: A Eurotransplant Cohort Study.

Recent studies raised the concern that warm ischemia during completion of vascular anastomoses in kidney implantation harms the transplant, but its precise impact on outcome and its interaction with other risk factors remain to be established. We investigated the relationship between anastomosis time and graft survival at 5 years after transplantation in 13 964 recipients of deceased donor solitary kidney transplants in the Eurotransplant region. Anastomosis time was independently associated with graft loss after adjusting for other risk factors (adjusted hazard ratio [HR] 1.10 for every 10-min increase, 95% confidence interval [CI] 1.06-1.14; p < 0.0001), whereas it did not influence recipient survival (HR 1.00, 95% CI 0.97-1.02). Kidneys from donation after circulatory death (DCD) were less tolerant of prolonged anastomosis time than kidneys from donation after brain death (p = 0.02 for interaction). The additive effect of anastomosis time with donor warm ischemia time (WIT) explains this observation because DCD status was no longer associated with graft survival when adjusted for this summed WIT, and there was no interaction between DCD status and summed WIT. Time to create the vascular anastomoses in kidney transplantation is associated with inferior transplant outcome, especially in recipients of DCD kidneys.

The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation.

Intestinal transplantation (ITx) remains challenged by frequent/severe rejections and immunosuppression-related complications (infections/malignancies/drug toxicity). We developed the Leuven Immunomodulatory Protocol (LIP) in the lab and translated it to the clinics. LIP consists of experimentally proven maneuvers, destined to promote T-regulatory (Tregs)-dependent graft-protective mechanisms: donor-specific blood transfusion (DSBT); avoiding high-dose steroids/calcineurin-inhibitors; and minimizing reperfusion injury and endotoxin translocation. LIP was tested in 13 consecutive ITx from deceased donors (2000-2014) (observational cohort study). Recipient age was 37 years (2.8-57 years). Five-year graft/patient survival was 92%. One patient died at 9 months due to aspergillosis, another at 12 years due to nonsteroidal anti-inflammatory drug-induced enteropathy. Early acute rejection (AR) developed in two (15%); late AR in three (23%); all were reversible. No chronic rejection (CR) occurred. No malignancies developed and estimated glomerular filtration rate remained stable post-Tx. At last follow-up (3.5 years [0.5-12.5 years]), no donor-specific antibodies were detected and 11 survivors were total parenteral nutrition free with a Karnofsky score >90% in 8 recipients (follow-up >1 years). A high frequency of circulating CD4+ CD45RA- Foxp3hi memory Tregs was found (1.8% [1.39-2.21]), comparable to tolerant kidney transplant (KTx) recipients and superior to stable immunosuppression (IS)-KTx, KTx with CR, and healthy volunteers. In this ITx cohort we show that DSBT in a low-inflammatory/pro-regulatory environment activates Tregs at levels similar to tolerant-KTx, without causing sensitization. LIP limits rejection under reduced IS and thereby prolongs long-term survival to an extent not previously attained after ITx.

Past, Present, and Future of Dynamic Kidney and Liver Preservation and Resuscitation.

The increased demand for organs has led to the increased usage of "higher risk" kidney and liver grafts. These grafts from donation after circulatory death or expanded criteria donors are more susceptible to preservation injury and have a higher risk of unfavorable outcomes. Dynamic, instead of static, preservation could allow for organ optimization, offering a platform for viability assessment, active organ repair and resuscitation. Ex situ machine perfusion and in situ regional perfusion in the donor are emerging as potential tools to preserve and resuscitate vulnerable grafts. Preclinical findings have ignited clinical organ preservation research that investigates dynamic preservation, its various modes (continuous, preimplantation) and temperatures (hypo-, sub, or normothermic). This review outlines the current status of dynamic preservation of kidney and liver grafts and describes ongoing research and emerging clinical trials.

Budd-Chiari syndrome: reassessment of a step-wise treatment strategy.

BACKGROUND AND STUDY AIMS: The Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction. A step-wise management was recently proposed. The aim of this study is to reassess our treatment approach and long-term outcome. PATIENTS AND METHODS: The data of 37 Budd-Chiari patients, seen in our unit, were critically analyzed and compared with the ENVIE (European Network For Vascular Disorders of the Liver) data. RESULTS: Most patients had multiple prothrombotic conditions (41%), of which an underlying myeloproliferative neoplasm was the most frequent (59%). The JAK2V617F mutation was associated with more complete occlusion of all hepatic veins (JAK2 mutation +: 70% vs JAK2 mutation -: 23% and a higher severity score. The step-wise treatment algorithm used in our unit, in function of the severity of the liver impairment and the number and the extension of hepatic veins occluded, resulted in the following treatments: only anticoagulation (n = 7.21%), recanalization procedure (n = 4.21%), portosystemic shunts (n = 9.26%) and liver transplantation (n = 14.44%). This resulted in a 10 year survival rate of 90%. Treatment of the underlying hemostatic disorder offered a low recurrence rate. None of the 21 patients with a myeloproliferative neoplasm died in relation to the hematologic disorder. CONCLUSIONS: An individualized treatment regimen consisting of anticoagulation and interventional radiology and/or transplantation when necessary and strict follow-up of the underlying hematologic disorder, provided an excellent long-term survival, which confirm the data of the ENVIE study.

The effect of anastomosis time on outcome in recipients of kidneys donated after brain death: a cohort study.

Whether warm ischemia during the time to complete the vascular anastomoses determines renal allograft function has not been investigated systematically. We investigated the effect of anastomosis time on allograft outcome in 669 first, single kidney transplantations from brain-dead donors. Anastomosis time independently increased the risk of delayed graft function (odds ratio per minute [OR] 1.05, 95% confidence interval [CI] 1.02-1.07, p < 0.001) and independently impaired allograft function after transplantation (p = 0.009, mixed-models repeated-measures analysis). In a subgroup of transplant recipients, protocol-specified biopsies at 3 months (n = 186), 1 year (n = 189), and 2 years (n = 153) were blindly reviewed. Prolonged anastomosis time independently increased the risk of interstitial fibrosis and tubular atrophy on these protocol-specified biopsies posttransplant (p < 0.001, generalized linear models). In conclusion, prolonged anastomosis time is not only detrimental for renal allograft outcome immediately after transplantation, also longer-term allograft function and histology are affected by the duration of this warm ischemia.

Xenon anaesthesia for patients undergoing off-pump coronary artery bypass graft surgery: a prospective randomized controlled pilot trial.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery carries a high risk for haemodynamic instability and perioperative organ injury. Favourable haemodynamic effects and organ-protective properties could render xenon an attractive anaesthetic for OPCAB surgery. The primary aim of this study was to assess whether xenon anaesthesia for OPCAB surgery is non-inferior to sevoflurane anaesthesia with regard to intraoperative vasopressor requirements. METHODS: Forty-two patients undergoing elective OPCAB surgery were enrolled in this prospective, single-blind, randomized controlled pilot trial. Patients were randomized to either xenon (50-60 vol%) or sevoflurane (1.1-1.4 vol%) anaesthesia. Primary outcome was intraoperative noradrenaline requirements necessary to achieve predefined haemodynamic goals. Secondary outcomes included safety variables such as the occurrence of adverse events (intraoperatively and during a 6-month follow-up after surgery) and the perioperative cardiorespiratory and inflammatory profile. RESULTS: Baseline and intraoperative data did not differ between groups. Xenon was non-inferior to sevoflurane, as xenon patients required significantly less noradrenaline intraoperatively to achieve the predefined haemodynamic goals {geometric mean 428 [95% confidence interval (CI) 312, 588] vs 1702 [1267, 2285] µg, P<0.0001}. No differences were found for safety. Significantly more sevoflurane patients developed postoperative delirium (POD) (hazard ratio 4.2, P=0.044). The average arterial pressure was lower in the sevoflurane group {median75 [interquartile range (IQR) 6] vs 72 [4] mmHg, P=0.002}. No differences were found for other haemodynamic parameters, the respiratory profile and the perioperative release of inflammatory cytokines, troponin T, serum protein S-100ß and erythropoietin. CONCLUSIONS: Compared with sevoflurane, xenon anaesthesia allows a significant reduction in vasopressor administration in OPCAB surgery. Moreover, xenon anaesthesia was associated with a lower risk for POD, a finding that has to be confirmed in larger studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01757106) and EudraCT (2012-002316-12).

Preoperative arterial embolization facilitates multivisceral transplantation for portomesenteric thrombosis.

Multivisceral transplantation (MvTx) for diffuse venous portomesenteric thrombosis is a surgically and anesthesiologically challenging procedure, partly because of the risk of massive bleeding during visceral exenteration. Preoperative visceral artery embolization might reduce this risk. In three consecutive MvTx, the celiac trunk (CT) and superior mesenteric artery (SMA) were embolized immediately pretransplant. We analyzed demographics, serum D-lactate, pH, base excess, hemoglobin, blood pressure, transfused packed cell (PC) units, intervention time and outcome. Results are reported as median (range). All recipients were male (43, 22, 47 years old). Portomesenteric thrombosis followed antiphospholipid syndrome, neuroendocrine tumor and liver cirrhosis. A peritransplant D-lactate peak of 6.1 (5.1-7.6) mmol/L, lowest pH of 7.24 (7.18-7.36) and lowest base excess level of -9.5 (-7.6 to -11.5) were observed. Values normalized within 3 h posttransplant. Embolization and exenteration times were 80 (70-90) min and 140 (130-165) min, respectively, during which blood pressure remained stable, lowest hemoglobin was 6.1 (6.1-7.6) g/dL and three (2-4) PC were administered. All procedures were uneventful. Follow-up was 7 (4-9) months. The first patient died 4 months post-MvTx after an intracranial bleeding; the other patients are doing well. Our experience suggests that preoperative embolization of CT and SMA facilitates native organ resection in MvTx.

Septuagenarian and octogenarian donors provide excellent liver grafts for transplantation.

BACKGROUND: Wider utilization of liver grafts from donors ≥ 70 years old could substantially expand the organ pool, but their use remains limited by fear of poorer outcomes. We examined the results at our center of liver transplantation (OLT) using livers from donors ≥ 70 years old. METHODS: From February 2003 to August 2010, we performed 450 OLT including 58 (13%) using donors ≥ 70 whose outcomes were compared with those using donors <70 years old. RESULTS: Cerebrovascular causes of death predominated among donors ≥ 70 (85% vs 47% in donors <70; P < .001). In contrast, traumatic causes of death predominated among donors <70 (36% vs 14% in donors ≥ 70; P = .002). Unlike grafts from donors <70 years old, grafts from older individuals had no additional risk factors (steatosis, high sodium, or hemodynamic instability). Both groups were comparable for cold and warm ischemia times. No difference was noted in posttransplant peak transaminases, incidence of primary nonfunction, hepatic artery thrombosis, biliary strictures, or retransplantation rates between groups. The 1- and 5-year patient survivals were 88% and 82% in recipients of livers <70 versus 90% and 84% in those from ≥ 70 years old (P = .705). Recipients of older grafts, who were 6 years older than recipients of younger grafts (P < .001), tended to have a lower laboratory Model for End-Stage Liver Disease score (P = .074). CONCLUSIONS: Short and mid-term survival following OLT using donors ≥ 70 yo can be excellent provided that there is adequate donor and recipient selection. Septuagenarians and octogenarians with cerebrovascular ischemic and bleeding accidents represent a large pool of potential donors whose wider use could substantially reduce mortality on the OLT waiting list.

Outcomes of liver transplantations using donations after circulatory death: a single-center experience.

INTRODUCTION: Orthotopic liver transplantation (OLT) (LTx) using donation after circulatory death (DCD) donors is increasingly performed, but still considered to risk of poorer outcomes compared with standard donations after brain death (DBD)-OLT. Therefore we reviewed our results of DCD-OLT. PATIENTS AND METHODS: Between 2003 and 2010, we performed 30 DCD-OLT (6% of all OLT). We retrospectively reviewed medical records of donors and recipients after DCD versus DBD-OLT to analyze biliary complications, retransplantation rates, and patient/graft survivals. RESULTS: Median donor age was similar for DCD and DBD-OLT: 51 versus 53 years (P = .244). Median donor warm ischemia time (stop ventilation to cold perfusion in DCD donors) was 24 minutes. Median cold ischemia time was shorter for DCD (6 hours 54 minutes) compared with DBD-OLT (8 hours 36 minutes; P < .0001). Median laboratory model of end-stage liver disease score was 15 for DCD, and 16 for DBD-OLT (P = .59). Median post-OLT Aspartate Aminotransferase (AST) peak was higher after DCD: 1178 versus DBD-OLT 651 IU/L (P = .005). The incidence of nonanastomotic strictures was different: 33.3% for DCD versus 12.5% for DBD-OLT (P = .001). The overall retransplantation rate was 3% after both DCD and DBD-OLT. After DCD-LTx actuarial 1, 3- and 5-year patient survivals were 93, 85 and 85%, and corresponding graft survivals, 90%, 82%, and 82% respectively, and not different compared with DBD-OLT: 88%, 78%, and 72% (P = .348) and 85%, 74%, and 68% (P = .524) respectively. CONCLUSION: Despite substantial ischemic injury (high peak AST and biliary strictures) short- and long-term survival after DCD-OLT was comparable to DBD-OLT. Rapid donor surgery, careful donor and recipient selection, as well as short warm and cold ischemia times are key factors to optimize outcomes after DCD-OLT. However, strategies to reduce biliary complications remain warranted.

Gastric outlet obstruction by a donor aortic tube after en bloc liver pancreas transplantation: a case report.

We present the case of a 30-year-old female suffering from a type five maturity onset diabetes of the young deficiency, resulting in type 1 diabetes and terminal renal insufficiency. She also had chronic and refractory pruritis due to primary sclerosing cholangitis-like fibrosis. She underwent combined en bloc liver and pancreas transplantation and kidney transplantation. The postoperative course was complicated by a gastric outlet obstruction due to compression of the native gastroduodenal junction by the donor aortic tube. This was treated by construction of a roux-en-Y gastrojejunostomy at posttransplant day 24. To our knowledge, compression of the gastroduodenal junction by a donor aortic tube after combined liver and pancreas (or multivisceral) transplantation has not been reported previously.

Neutrophil gelatinase-associated lipocalin, a new biomarker candidate in perfusate of machine-perfused kidneys: a porcine pilot experiment.

The enduring kidney graft shortage has led to the increasing use of expanded-criteria donors as well as kidneys donated after cardiac death, triggering the revival of machine perfusion preservation. Indeed, machine perfusion not only preserves these kidneys better than static cold storage, but also has the potential to evaluate them. The presence of certain biomarkers, among them aspartate aminotransferase (AST) and heart-type fatty acid binding protein (H-FABP), has been demonstrated in the perfusate of human kidneys, making them potentially useful as biomarkers of graft quality. Neutrophil gelatinase-associated lipocalin (NGAL) which is believed to be released upon renal tubular cell injury is another biomarker candidate. However, because it is also released from neutrophils, it is currently unclear whether NGAL is a direct or indirect, inflammatory-mediated marker of kidney injury. To resolve this issue we established a pilot experiment to study the concentrations of AST, H-FABP, and NGAL in the perfusates of 6 porcine kidneys that were exposed to incremental periods of warm ischemia before machine perfusion for 22 hours. An ex vivo porcine model was chosen because preclinical large animal work remains necessary to refine machine perfusion technology and because the presence of these markers in perfusates of porcine kidneys had not been shown previously. All 3 biomarkers were detectable in the cold acellular perfusate; their release seemed to be proportionate to the degree of warm injury, albeit that this must be confirmed in a larger sample. In conclusion, NGAL is directly released by ischemically damaged kidneys, independent of neutrophil activation. In addition to NGAL, the determination of AST and H-FABP in perfusates of machine-perfused porcine kidneys is also feasible. Determination of these markers may be added to the arsenal of research tools for preclinical preservation research.

The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys.

Vascular renal resistance (RR) during hypothermic machine perfusion (HMP) is frequently used in kidney graft quality assessment. However, the association between RR and outcome has never been prospectively validated. Prospectively collected RR values of 302 machine-perfused deceased donor kidneys of all types (standard and extended criteria donor kidneys and kidneys donated after cardiac death), transplanted without prior knowledge of these RR values, were studied. In this cohort, we determined the association between RR and delayed graft function (DGF) and 1-year graft survival. The RR (mmHg/mL/min) at the end of HMP was an independent risk factor for DGF (odds ratio 38.1 [1.56-934]; p = 0.026) [corrected] but the predictive value of RR was low, reflected by a c-statistic of the receiver operator characteristic curve of 0.58. The RR was also found to be an independent risk factor for 1-year graft failure (hazard ratio 12.33 [1.11-136.85]; p = 0.004). Determinants of transplant outcome are multifactorial in nature and this study identifies RR as an additional parameter to take into account when evaluating graft quality and estimating the likelihood of successful outcome. However, RR as a stand-alone quality assessment tool cannot be used to predict outcome with sufficient precision.