Can CT or MRI volumetry substitute scintigraphy in living kidney donor evaluation? A systematic review.

BACKGROUND: Current potential living kidney donor's assessment includes functional and anatomical evaluation. Scintigraphy is recommended in some cases and some centers include this test in the donor's protocol. Recent studies advocate for the avoidance of this test as CT or MRI volumetry showed to accurately assess donor's renal function. OBJECTIVE: To summarize scientific evidence on image tests for pre-donation and/or post-nephrectomy renal function evaluation. EVIDENCE ACQUISITION: This review followed the guidelines set by the European Association of Urology and adhered to PRISMA 2020 recommendations. The protocol was registered in PROSPERO on 10th December 2022 (ID: CRD42022379273). EVIDENCE SYNTHESIS: Twenty-one studies met the inclusion criteria after thorough screening and eligibility assessment. According to QUADAS-2, patient selection and flow/timing domains showed a predominant low risk of bias. The correlation between split renal function (SRF) using CT and scintigraphy varied from weak (r = 0.21) to remarkably strong (r = 0.949). Bland-Altman agreement demonstrated moderate to excellent results, with mean differences ranging from -0.06% to 1.76%. The correlation between split renal volume (CT) and estimated glomerular filtration rate (eGFR) at 6 months or 1 year after nephrectomy showed a moderate correlation, with coefficients ranging from 0.708 to 0.83. The correlation between SRF (MRI) and renal scintigraphy reported a moderate correlation, with correlation coefficients of 0.58 and 0.84. MRI and scintigraphy displayed a good agreement, with a 66% agreement observed and mean differences of ± 0.3%. CONCLUSIONS: Despite study heterogeneity, MRI or CT-based renal volumetry appears promising compared to scintigraphy, with favorable correlations and agreement.

Simultaneous liver-kidney transplantation: future perspective.

BACKGROUND: The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. METHOD: Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. RESULTS:  A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. CONCLUSIONS:  Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual-organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation.

Graft survival and postoperative complications following orthotopic renal transplantation.

The iliac fossa is the most commonly used site to place the graft in renal transplantation in adults. However, iliac fossa may not be used in various conditions. Thus, orthotopic renal transplantation becomes a viable alternative for these selected patients. Given the technically challenging surgery and limited number of patients, data on the long-term outcomes on this regard are scarce. This narrative review serves as an update on the clinical outcomes after orthotopic renal transplantation, focusing on overall recipient survival and renal graft survival, as well as postoperative complications. We found that studies to date showed a comparable survival rate in both recipients and renal grafts in the postoperative follow-up period after orthotopic renal transplantation with a lower complication rate compared to the published data on heterotopic renal transplantation. The results of our review may encourage transplant centers to reevaluate their policies to consider orthotopic renal transplantation as an alternative technique in cases where heterotopic kidney transplantation is not possible.

Kidney transplantation from elderly donors (> 70 years): a systematic review.

PURPOSE: The incidence of kidney transplants from elderly donors over 70 years of age has increased significantly over the past 10 years to reach 20% of available kidney graft in some European countries. However, there is little data available on the outcomes of transplants from these donors. We performed a systematic review to evaluate the outcomes of transplantation from donors over 70 years of age. METHODS: A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline, Embase, and Cochrane databases were searched to identify all studies reporting outcomes on kidney transplants from donors over 70 years. Due to the heterogeneity of the studies, a meta-analysis could not be performed. RESULTS: A total of 29,765 patients in 27 studies were included. The mean donors age was 74.79 years, and proportion of kidney graft from women was 53.54%. The estimated 1- and 5-year kidney death-censored graft survivals from donors > 70 years old were, respectively, 85.95 and 80.27%, and the patient survivals were 90.88 and 71.29%. The occurrence of delayed graft function was 41.75%, and primary non-function was 4.67%. Estimated graft function at 1 and 5 years was 36 and 38 mL/min/1.73 m2. Paucity data were available on post-operative complications. CONCLUSIONS: Elderly donors appear to be a reliable source of grafts. However, these transplants are associated with a high rate of delayed graft function without repercussion on long-term graft survival. Allocation strategy to elderly recipients is the main factor of decreased recipient survival.

Systematic review of techniques and devices used to avoid warm ischemia time injury during kidney transplantation.

PURPOSE: The lack of a reliable and reproducible technique to ensure a constantly low temperature of the graft during kidney transplantation (KT) may be a cause of renal nonfunction. The aim of this review was to assess all the methods and devices available to ensure hypothermia during vascular anastomosis in KT. METHODS: A literature search was conducted through May 2022 using PubMed/Medline, Cochrane Library, Embase and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The review protocol was registered on PROSPERO (CRD42022326550). RESULTS: A total of 20 studies reporting on four hypothermia techniques met our inclusion criteria. Simple instillation of cold serum is not sufficient, the graft reaching up to 33 ℃ at the end of warm ischemia time (WIT). Plastic bags filled with ice slush have questionable efficiency. The use of a gauze jacket filled with ice-slush was reported in 12/20 studies. It ensures a graft temperature up to 20.3 ℃ at the end of WIT. Some concerns have been linked to potentially inhomogeneous parenchymal cooling and secondary ileus. Novel devices with continuous flow of ice-cold solution around the graft might overcome these limitations, showing a renal temperature below 20 ℃ at all times during KT. CONCLUSION: The gauze filled with ice slush is the most common technique, but several aspects can be improved. Novel devices in the form of cold-ischemia jackets can ensure a lower and more stable temperature of the graft during KT, leading to higher efficiency and reproducibility.

Effectiveness of endourological management of ureteral stenosis in kidney transplant patients: EAU-YAU kidney transplantation working group collaboration.

PURPOSE: Ureteral stenosis (US) in kidney transplant (KT) recipients is associated with poorer long-term graft survival. Surgical repair is the standard of care, and endoscopic treatment represents an alternative for stenosis < 3 cm. We aimed to determine the effectiveness and safety of endourological management of US in KT patients and predictors of failure. METHODS: A retrospective multicenter study was conducted in four European referral centers, including all KT patients with US managed endoscopically between 2009 and 2021. Clinical success was defined as the absence of upper urinary tract catheterization, surgical repair or transplantectomy during follow-up. RESULTS: A total of 44 patients were included. The median time to US onset was 3.5 months (IQR 1.9-10.8), the median length of stricture was 10 mm (IQR 7-20). Management of US involved balloon dilation and laser incision in 34 (79.1%) and 6 (13.9%) cases, respectively, while 2 (4.7%) received both. Clavien-Dindo complications were infrequent (10%); only one Clavien ≥ III complication was reported. Clinical success was 61% at last follow-up visit (median = 44.6 months). In the bivariate analysis, duckbill-shaped stenosis (vs. flat/concave) was associated with treatment success (RR = 0.39, p = 0.04, 95% CI 0.12-0.76), while late-onset stenosis (> 3 months post KT) with treatment failure (RR = 2.00, p = 0.02, 95% CI 1.01-3.95). CONCLUSIONS: Considering the acceptable long-term results and the safety of these procedures, we believe that the endoscopic treatment should be offered as a first-line therapy for selected KT patients with US. Those with a short and duckbill-shaped stenosis diagnosed within 3 months of KT seem to be the best candidates.

3D-Image guided robotic-assisted partial nephrectomy: a multi-institutional propensity score-matched analysis (UroCCR study 51).

PURPOSE: Robot-assisted partial nephrectomy (RAPN) is a difficult procedure with risk of significant perioperative complications. The objective was to evaluate the impact of preoperative planning and intraoperative guidance with 3D model reconstructions on perioperative outcomes of RAPN. METHODS: We conducted a retrospective analysis of all patients who underwent RAPN for kidney tumor by three high-volume expert surgeons from academic centers. Clinical data were collected prospectively after written consent into the French kidney cancer network database UroCCR (CNIL-DR 2013-206; NCT03293563). Our cohort was divided into two groups: 3D-Image guided RAPN group (3D-IGRAPN) and control group. A propensity score according to age, pre-operative renal function and RENAL tumor complexity score was used. Both surgical techniques were compared in terms of perioperative outcomes. RESULTS: The initial study cohort included 230 3D-IGRAPN and 415 control RAPN. Before propensity-score matching, patients in the 3D-IGRAPN group had a larger tumor (4.3 cm vs. 3.5 cm, P < 0.001) and higher RENAL complexity score (9 vs. 8, P < 0.001). Following propensity-score matching, there were 157 patients in both groups. The rate of major complications was lower for patients in the 3D-IGRAPN group (3.8% vs. 9.5%, P = 0.04). The median percentage of eGFR variation recorded at first follow-up was lower in the 3D-IGRAPN group (- 5.6% vs. - 10.5%, P = 0.002). The trifecta achievement rate was higher in the 3D-IGRAPN group (55.7% vs. 45.1%; P = 0.005). CONCLUSION: Three-dimensional kidney reconstructions use for pre-operative planning and intraoperative surgical guidance lowers the risk of complications and improve perioperative clinical outcomes of RAPN.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p = .03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Psychological Impact of Living Kidney Donation: A Systematic Review by the EAU-YAU Kidney Transplant Working Group.

We performed a systematic literature review of the psychological impact on donors of living kidney donation. We conducted a literature review in PubMed/Medline according to PRISMA guidelines which included both qualitative (based on interviews) and quantitative studies (based on standardized questionnaire). There were 15 quantitative studies and 8 qualitative studies with 2,732 donors. Given that the methodologies of qualitative and quantitative studies are fundamentally different, we narratively synthetized results of studies according to four axes: quality of life, anxiety/depression, consequences of donation on the donor/recipient relationship, overall satisfaction and regret. The quantitative studies reported that donor quality of life remained unchanged or improved. Donor regret rates were very low and donor-recipient relationships also remained unchanged or improved. Qualitative studies reported more complex donation experiences: one can regret donation and still decide to recommend it as in a social desirability bias. In both study types, donor-recipient relationships were closer but qualitative studies reported that post-donation rebonding was required. The qualitative studies therefore highlighted the psychological complexity of donation for donors, showing that living donation impacts the donor's life whether it is successful or not. A better understanding of the impact of donation on donors could provide better care for donors.

Management and Outcome After Early Renal Transplant Vein Thrombosis: A French Multicentre Observational Study of Real-Life Practice Over 24 Years.

Early (<14 days) renal transplant vein thrombosis posttransplant (eRVTPT) is a rare but threatening complication. We aimed to assess eRVTPT management and the rate of functional renal transplantation. Of 11,172 adult patients who had undergone transplantation between 01/1997 and 12/2020 at 6 French centres, we identified 176 patients with eRVTPT (1.6%): 16 intraoperative (Group 1, G1) and 160 postoperative (Group 2, G2). All but one patient received surgical management. Patients in group G2 had at least one imaging test for diagnostic confirmation (N = 157, 98%). During the operative management of the G2 group, transplantectomy for graft necrosis was performed immediately in 59.1% of cases. In both groups, either of two techniques was preferred, namely, thrombectomy by renal venotomy or thrombectomy + venous anastomosis repair, with no difference in the functional graft rate (FGR) at hospital discharge (p = NS). The FGR was 62.5% in G1 and 8.1% in G2 (p < 0.001). Numerous complications occurred during the initial hospitalization: 38 patients had a postoperative infection (21.6%), 5 experienced haemorrhagic shock (2.8%), 29 exhibited a haematoma (16.5%), and 97 (55.1%) received a blood transfusion. Five patients died (2.8%). Our study confirms the very poor prognosis of early renal graft venous thrombosis.

Sterile Pancreas Inflammation during Preservation and after Transplantation.

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response.

Postoperative surgical complications after pediatric kidney transplantation in low weight recipients (<15 kg): a systematic review.

PURPOSE OF REVIEW: Kidney transplantation in low-weight recipients (<15 kg) is a challenging surgery with special characteristics. We proposed to perform a systematic review to determine the postoperative complication rate and the type of complications after kidney transplantation in low-weight recipients (<15 kg). The secondary objectives were to determine graft survival, functional outcomes, and patient survival after kidney transplantation in low-weight recipients. METHODS: A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline and Embase databases were searched to identify all studies reporting outcomes on kidney transplantation in low-weight recipients (<15 kg). RESULTS: A total of 1254 patients in 23 studies were included. The median postoperative complications rate was 20.0%, while 87.5% of those were major complications (Clavien ≥3). Further, urological and vascular complications rates were 6.3% (2.0-11.9) and 5.0% (3.0-10.0), whereas the rate of venous thrombosis ranged from 0 to 5.6%. Median 10-year graft and patient survival were 76 and 91.0%. SUMMARY: Kidney transplantation in low-weight recipients is a challenging procedure complicated by a high rate of morbidity. Finally, pediatric kidney transplantation should be performed in centers with expertise and multidisciplinary pediatric teams.

Kidney transplantation from expanded criteria donors: an increased risk of urinary complications - the UriNary Complications Of Renal Transplant (UNyCORT) study.

OBJECTIVES: To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS: The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Données Informatisées et VAlidées en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS: Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P < 0.001) and especially with stenosis and ureteric fistulae at 1 year. There is no association with LD, uncontrolled and controlled DCD. The placement of an endo-ureteric stent was beneficial in preventing urinary complications in all donors and particularly in ECD donors. CONCLUSION: The donor's ECD status is associated with a higher likelihood of stenosis and ureteric fistulae at 1 year. Recipients of grafts from ECD donors should probably be considered for closer urological monitoring and systematic preventive measures.

Systematic review on oncologic outcomes on adjuvant endovesical treatment for non-muscle invasive bladder cancer in patients with solid organ transplant.

PURPOSE: Urothelial carcinoma has a higher incidence in renal transplanted patients according to several registries (relative risk × 3), and the global prognosis is inferior to the general population. The potential impact of immunosuppressive therapy on the feasibility, efficacy, and complications of endovesical treatment, especially Bacillus Calmette-Guerin, has a low level of evidence. We performed a systematic review that aimed to assess the morbidity and oncological outcomes of adjuvant endovesical treatment in solid organ transplanted patients. METHODS: Medline was searched up to December 2021 for all relevant publications reporting oncologic outcomes of endovesical treatment in solid organ transplanted patients with NMIBC. Data were synthesized in light of methodological and clinical heterogeneity. RESULTS: Twenty-three retrospective studies enrolling 238 patients were included: 206 (96%) kidney transplants, 5 (2%) liver transplants, and 2 (1%) heart transplants. Concerning staging: 25% were pTa, 62% were pT1, and 22% were CIS. 140/238 (59%) patients did not receive adjuvant treatment, 50/238 (21%) received mitomycin C, 4/238 (2%) received epirubicin, and 46/238 (19%) received BCG. Disease-free survival reached 35% with TURBT only vs. 47% with endovesical treatment (Chi-square test p = 0.08 OR 1.2 [0.98-1.53]). The complication rate of endovesical treatment was 12% and was all minor (Clavien-Dindo I). CONCLUSION: In solid organ transplanted patients under immunosuppressive treatment, both endovesical chemotherapy and BCG are safe, but the level of evidence concerning efficacy in comparison with the general population is low. According to these results, adjuvant treatment should be proposed for NMIC in transplanted patients as in the general population.

[Pedagogical impact of a MOOC on surgical technique of kidney transplantation]. / Impact pédagogique d'un MOOC de technique chirurgicale de transplantation rénale.

OBJECTIVE: To evaluate the educational impact of a pilot MOOC (Massive Open Online Course), validated by the French College of Urology Teachers (FCUT), on the surgical technique of kidney transplantation. MATERIALS AND METHODS: We developed a MOOC on the surgical technique of kidney transplantation, based on a video of a surgical procedure, performed by an expert surgeon. The MOOC has been validated by the FCUT. We have created 2 student groups: 1) MOOC-pre-QCM group: visualization of the MOOC then answer to the MCQs and satisfaction questions; 2) MOOC-post-QCM group: answer to the MCQs then visualization of the MOOC then answers to the satisfaction questions. In total, 20 MCQs on the kidney transplantation technique were completed by the 2 groups. The answers were anonymous. RESULTS: A total of 142 people answered the MCQs (MOOC-pre-QCM group (n=66) and MOOC-post-QCM group (n=76)). Twenty-nine percent (41/142) of the participants were fellows and 71 % (101/142) were residents. The proportion of fellows and residents was identical between the 2 groups. The rate of correct answers to the 20 MCQs was statistically higher in the MOOC-pre-QCM group, compared to the MOOC-post-QCM group (88.6 % versus 73.3 %, P<0.0001). Ninety-one percent of students found the MOOC "Very Useful" or "Useful". The median MOOC rating, given by students, was 8/10. CONCLUSION: This study showed a positive impact of the MOOC on theoretical knowledge of kidney transplantation surgical technique. This MOOC could serve as a pilot project for the development of other MOOCs on urological surgery. LEVEL: 3.

Robotic-assisted kidney transplantation in obese recipients compared to non-obese recipients: the European experience.

PURPOSE: The main objective was to compare minor (Clavien I-II) and major (Clavien ≥ III) intra- and postoperative complications of living donor robotic assisted kidney transplantation (RAKT) in obese (≥ 30 kg/m2 BMI), overweight (< 30/ ≥ 25 kg/m2 BMI) and non-overweight recipients (< 25 kg/m2 BMI). METHODS: For the present retrospective study, we reviewed the multi-institutional ERUS-RAKT database to select consecutive living donor RAKT recipients. Functional outcomes, intra- and postoperative complications were compared between obese, overweight and non-overweight recipients. RESULTS: 169 living donor RAKTs were performed, by 10 surgeons, from July 2015 to September 2018 in the 8 European centers. 32 (18.9%) recipients were obese, 66 (39.1%) were overweight and 71 (42.0%) were non-overweight. Mean follow-up was 1.2 years. There were no major intra-operative complications in either study group. Conversion to open surgery occurred in 1 obese recipient, in 2 overweight recipients and no conversion occurred in non-overweight recipients (p = 0.3). Minor and major postoperative complications rates were similar in the 3 groups. At one-year of follow-up, median eGFR was similar in all groups [54 (45-60) versus 57 (46-70) versus 63 (49-78) ml/min/1.73 m2 in obese, overweight and non-overweight recipient groups, respectively, p = 0.5]. Delayed graft function rate was similar in the 3 groups. Only the number of arteries was an independent predictive factor of suboptimal renal function at post-operative day 30 in the multivariate analysis. CONCLUSION: RAKT in obese recipients is safe, compared to non-overweight recipients and yields very good function, when it performed at high-volume referral centers by highly trained transplant teams.

Successful pancreas allotransplantations after hypothermic machine perfusion in a novel diabetic porcine model: a controlled study.

The standard technique for pancreas preservation for transplantation is static cold storage (SCS). In this experimental study, we compare SCS to hypothermic machine perfusion (HMP) of the pancreas to assess if the latter could safely prolong the ischaemia period prior to transplantation. We worked in two phases, first with organ preservation for 24 h and second, preservation for either 2 or 6 h before allotransplantation. In phase 1, exocrine injury markers were found to be nonsignificantly lower, in the HMP group (n = 3) vs. SCS (n = 3) after 24 h of preservation; amylase (P = 0.2), lipase (P = 0.3) and lactate dehydrogenase (P = 0.1). In phase 2, 14 recipient diabetic pigs (after total pancreatectomy) received allotransplantations with n = 4 and n = 4 pancreases after HMP for 2 and 6 h vs. n = 3 and n = 3 pancreases after SCS for 2 and 6 h, respectively. There were no differences in recipient survival (P = 0.7), and mean survival was 14 days (0-53 days). All recipients had allograft function defined as detectable C-peptide and independent normoglycemia. We have not highlighted vascular thrombosis in all allotransplantations. This study reports the first successful pancreas allotransplantation after HMP preservation for up to 6 h with no evidence of graft thrombosis.

Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.

Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.

Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation.

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.

Ex situ hypothermic perfusion of nonhuman primate pancreas: A feasibility study.

Pancreatic static cold storage (SCS) is the gold-standard method for pancreas preservation. Our main objective was to evaluate feasibility of hypothermic perfusion (HP) of nonhuman primates' pancreases for potential organ transplantation. Seven baboon pancreases were tested. Animals were included in a study approved by the French Research Ministry of Health. Two groups were compared: the control group (n = 2) was preserved using conventional SCS for 24-h and the perfusion group (n = 5) used HP for 24-h, with three different perfusion pressures (PP): 15 (n = 3), 20 (n = 1), and 25 mm Hg (n = 1). In the control group, focal congestion of islets was observed after 6-h. At 24-h, ischemic necrosis and multifocal congestion also occurred. In the HP group, at 15 mm Hg PP, multifocal congestion of islets was present at 24-h. At 20 mm Hg PP, no ischemic necrosis was found after 6-h. At 12-h and 24-h, focal congestion of islets was seen. At 25 mm Hg PP, focal congestion of islets appeared after 12-h. Immunostaining for insulin, glucagon, and somatostatin was normal and similar in controls and perfused pancreas transplants even after 24-h. Apoptosis index represented by cleaved caspase 3 activity, was less than 1% in perfusion and control groups, even after 24-h. HP of nonhuman primate pancreas is feasible and not deleterious as far as 24-h compared to SCS. SCS for more than 12-h was harmful for the transplants. Systolic perfusion pressure between 15-20 mm Hg did not cause any pathological injury of the tested organs.