First clinical kidney transplantation series using brief bubble and direct surface oxygenation as alternative for membrane oxygenation during hypothermic machine perfusion.

BACKGROUND: Active oxygen during hypothermic machine perfusion has the potential to improve mitochondrial preservation and subsequently decrease the harmful effects of ischemia reperfusion injury. Brief bubble, and subsequent surface oxygenation are an alternative oxygenation technique for membrane-oxygenated kidneys during hypothermic machine perfusion (HMP). METHODS: Between March 20, 2022, and June 13, 2022, 5 kidney grafts originating from 3 donors after circulatory death were oxygenated by bubble and surface oxygenation during HMP. RESULTS: No adverse events related to this new oxygenation technique were observed. All five recipients experienced no dialysis-dependency after transplantation with excellent initial graft function at 3 months after transplantation. CONCLUSIONS: For the first time in human, this new oxygenation technique was successfully applied to 5 HMP-kidneys, originating from donation after circulatory death. If confirmed on larger scale cohorts, this innovative oxygenation technique, as alternative oxygenation technique for membrane-oxygenated kidneys, has the potential to be widely implemented because its simplicity and efficacy, and reducing economic and ecological costs by eliminating the need for a membrane oxygenator and oxygen source during transport.

miR-199a Downregulation as a Driver of the NOX4/HIF-1α/VEGF-A Pathway in Thyroid and Orbital Adipose Tissues from Graves' Patients.

Graves' disease (GD) is an autoimmune thyroiditis often associated with Graves' orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats.

Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis.

In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT.

Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model.

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O2 uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia-reperfusion autotransplant model.

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.

Preperitoneal Surgical Approach to Treat Vesicoureteral Anastomotic Leakage, Distal Stenosis or Reflux After Kidney Transplantation.

BACKGROUND: If endourological approaches are not applicable to treat vesicoureteral anastomotic complications after kidney transplantation, the surgical gold standard in many transplant centers is pyeloureterostomy or ureteroureterostomy using the native ureter. We report an original preperitoneal technique that can be used for vesicoureteral reanastomosis in kidney transplant recipients not eligible for endourological treatment. METHODS: Between January 2011 and December 2015, 18 kidney transplant recipients underwent this new surgical procedure. Of this number, 15 subjects with at least 1 year of follow-up were included in the analysis. The indications were vesicoureteral reflux, anastomotic stenosis, and leakage in 8, 5, and 2 patients, respectively. Briefly, a double J stent was preoperatively inserted into the grafted ureter. Surgery was performed through a Pfannenstiel incision. The preperitoneal space surrounding the bladder was dissected and the distal part of the grafted ureter was identified and mobilized. The anastomotic area was resected and another vesicoureteral anastomosis was performed (Lich-Gregoir technique), keeping the JJ stent in place for three weeks. RESULTS: This procedure was performed 213 days (range 17-2608) after kidney transplantation. Median surgical duration was 179 minutes (range 112-314) and median hospital stay 8 days (range 4-14). The success rate was 86.7% (13/15), with a median follow-up of 1148 days (range 517-1808). In two patients, symptomatic recurrence of vesicoureteral reflux required a pyeloureterostomy using the native ureter. CONCLUSIONS: The authors describe a simple technique that avoids transperitoneal dissection, potentially yielding more esthetic results thanks to easy access, as well as excellent outcomes.

Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.

For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effector function and TCR-CD8 colocalization were restored with galectin disaccharide ligands, suggesting that the binding of TCR to galectin plays a role in the distancing of TCR from CD8. These findings appear to be applicable in vivo, as TCR was observed to be distant from CD8 on human tumor-infiltrating lymphocytes, which were anergic. These lymphocytes recovered effector functions and TCR-CD8 colocalization after ex vivo treatment with galectin disaccharide ligands. The separation of TCR and CD8 molecules could be one major mechanism of anergy in tumors and other chronic stimulation conditions.

Unusual presentations of enlarged parathyroid cysts: two case reports.

INTRODUCTION: Parathyroid cysts are infrequently encountered and have a variable presentation pattern depending on their size, location and secreting character. PATIENTS AND METHODS: We report two cases of parathyroid cysts characterized by their uncommon clinical presentation. RESULTS: In the first case the patient presented with a large cervical cystic mass without hypercalcemia, while in the second case, the patient experienced a hypercalcemic crisis associated with acute renal failure. The variable pattern of clinical manifestations is discussed. CONCLUSION: Parathyroid cysts are a rare entity. Surgical resection is the key to therapy when hyperparathyroidism or local compression are identified.

High-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.

BACKGROUND: In the Eurotransplant Kidney Allocation System (ETKAS), transplant candidates can be considered for high-urgency (HU) status in case of life-threatening inability to undergo renal replacement therapy. Data on the outcomes of HU transplantation are sparse and the benefit is controversial. METHODS: We systematically analysed data from 898 ET HU kidney transplant recipients from 61 transplant centres between 1996 and 2010 and investigated the 5-year patient and graft outcomes and differences between relevant subgroups. RESULTS: Kidney recipients with an HU status were younger (median 43 versus 55 years) and spent less time on the waiting list compared with non-HU recipients (34 versus 54 months). They received grafts with significantly more mismatches (mean 3.79 versus 2.42; P < 0.001) and the percentage of retransplantations was remarkably higher (37.5 versus 16.7%). Patient survival (P = 0.0053) and death with a functioning graft (DwFG; P < 0.0001) after HU transplantation were significantly worse than in non-HU recipients, whereas graft outcome was comparable (P = 0.094). Analysis according to the different HU indications revealed that recipients listed HU because of an imminent lack of access for dialysis had a significantly worse patient survival (P = 0.0053) and DwFG (P = 0.0462) compared with recipients with psychological problems and suicidality because of dialysis. In addition, retransplantation had a negative impact on patient and graft outcome. CONCLUSIONS: Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.

Impact of POR*28 on the pharmacokinetics of tacrolimus and cyclosporine A in renal transplant patients.

BACKGROUND: The P450 oxidoreductase (POR)*28 variant allele has been associated with altered cytochrome P450 3A enzyme activities. Both CYP3A5 and CYP3A4 are involved in the metabolism of calcineurin inhibitors and recent data show that POR*28 may explain part of the variability observed in tacrolimus (Tac) pharmacokinetics. The aim of this study was to investigate the impact of the POR*28 allele on Tac and cyclosporine A (CsA) immunosuppressive therapies. METHODS: Kidney transplant recipients receiving either Tac (n = 184) or CsA (n = 174), participating in a prospective multicenter trial, were genotyped for POR*28, CYP3A4*22, and CYP3A5*3. RESULTS: CYP3A5 expressers that were carriers of at least 1 POR*28 allele had a 16.9% decrease in dose-adjusted predose concentrations when compared CYP3A5 expressers that carried the POR*1/*1 genotype (P = 0.03), indicating an increased CYP3A5 activity for POR*28 carriers. In CYP3A5, nonexpressers carrying 2 POR*28 alleles, a 24.1% (confidence interval95% = -39.4% to -4.9%; P = 0.02) decrease in dose-adjusted predose concentrations was observed for Tac, suggesting higher CYP3A4 activity. For CsA, POR*28/*28 patients not expressing CYP3A5 and not carrying the CYP3A4*22 decrease-of-function allele showed 15% lower CsA dose-adjusted predose concentrations (P = 0.01), indicating also increased CYP3A4 activity. In both cohorts (ie, Tac and CsA), the POR*28 allele was neither associated with the incidence of delayed graft function nor with biopsy-proven acute rejection. These results were further confirmed in 2 independent cohorts. CONCLUSIONS: Our results show that the POR*28 allele is associated with increased in vivo CYP3A5 activity for Tac in CYP3A5 expressers, whereas POR*28 homozygosity was associated with a significant higher CYP3A4 activity in CYP3A5 nonexpressers for both Tac and CsA.

Tacrolimus Pharmacokinetics is Associated with Gut Microbiota Diversity in Kidney Transplant Patients: Results from a Pilot Cross-Sectional Study.

Clinical use of tacrolimus (TAC), an essential immunosuppressant following transplantation, is complexified by its high pharmacokinetic (PK) variability. The gut microbiota gains growing interest but limited investigations have evaluated its contribution to TAC PKs. Here, we explore the associations between the gut microbiota composition and TAC PKs. In this pilot cross-sectional study (Clinicaltrial.gov NCT04360031), we recruited 93 CYP3A5 non-expressers stabilized kidney transplant recipients. Gut microbiota composition was characterized by 16S rRNA gene sequencing, TAC PK parameters were computed, and additional demographic and medical covariates were collected. Associations between PK parameters or diabetic status and the gut microbiota composition, as reflected by α- and ß-diversity metrics, were evaluated. Patients with higher TAC area under the curve AUC/(dose/kg) had higher bacterial richness, and TAC PK parameters were associated with specific bacterial taxa (e.g., Bilophila) and amplicon sequence variant (ASV; e.g., ASV 1508 and ASV 1982 (Veillonella/unclassified Sporomusaceae); ASV 664 (unclassified Oscillospiraceae)). Building a multiple linear regression model showed that ASV 1508 (co-abundant with ASV 1982) and ASV 664 explained, respectively, 16.0% and 4.6% of the interindividual variability in TAC AUC/(dose/kg) in CYP3A5 non-expresser patients, when adjusting for hematocrit and age. Anaerostipes relative abundance was decreased in patients with diabetes. Altogether, this pilot study revealed unprecedented links between the gut microbiota composition and diversity and TAC PKs in stable kidney transplant recipients. It supports the relevance of studying the gut microbiota as an important contributor to TAC PK variability. Elucidating the causal relationship will offer new perspectives to predict TAC inter- and intra-PK variability.

Exploring Preservation Modalities in a Split Human Pancreas Model to Investigate the Effect on the Islet Isolation Outcomes.

Background: In islet transplantation, the use of dynamic hypothermic preservation techniques is a current challenge. This study compares the efficacy of 3 pancreas preservation methods: static cold storage, hypothermic machine perfusion (HMP), and oxygenated HMP. Methods: A standardized human pancreas split model was employed using discarded organs from both donation after brain death (n = 15) and donation after circulatory death (DCD) (n = 9) donors. The pancreas head was preserved using static cold storage (control group), whereas the tail was preserved using the 3 different methods (study group). Data on donor characteristics, pancreas histology, isolation outcomes, and functional tests of isolated islets were collected. Results: Insulin secretory function evaluated by calculating stimulation indices and total amount of secreted insulin during high glucose stimulation (area under the curve) through dynamic perifusion experiments was similar across all paired groups from both DCD and donation after brain death donors. In our hands, islet yield (IEQ/g) from the pancreas tails used as study groups was higher than that of the pancreas heads as expected although this difference did not always reach statistical significance because of great variability probably due to suboptimal quality of organs released for research purposes. Moreover, islets from DCD organs had greater purity than controls (P ≤ 0.01) in the HMP study group. Furthermore, our investigation revealed no significant differences in pancreas histology, oxidative stress markers, and apoptosis indicators. Conclusions: For the first time, a comparative analysis was conducted, using a split model, to assess the effects of various preservation methods on islets derived from pancreas donors. Nevertheless, no discernible variances were observed in terms of islet functionality, histological attributes, or isolation efficacy. Further investigations are needed to validate these findings for clinical application.

Donor- and isolation-related predictive factors of in vitro secretory function of cultured human islets.

Background and aims: Human islet preparations designated for research exhibit diverse insulin-secretory profiles. This study aims to assess the impact of donor- and isolation-related factors on in vitro islet secretory function. Methods: A retrospective analysis of 46 isolations from 23 pancreata discarded for clinical transplantation was conducted. In vitro islet secretory function tests were performed on Day 1 and Day 7 of culture. Linear mixed-effects models (LMMs) were employed to investigate the relationships between various predictors characterizing the patient and donor characteristics as well as the isolation effectiveness and two functional outcomes including the islet stimulation index (SI) and area under the insulin curve (AUC). Fixed effects were introduced to represent the main effects of each predictor, and backward elimination was utilized to select the most significant fixed effects for the final model. Interaction effects between the timepoint (Day 7 vs. Day 1) and the predictors were also evaluated to assess whether predictors were associated with the temporal evolution of SI and AUC. Fold-change (Fc) values associated with each predictor were obtained by exponentiating the corresponding coefficients of the models, which were built on log-transformed outcomes. Results: Analysis using LMMs revealed that donor body mass index (BMI) (Fc = 0.961, 95% CI = 0.927-0.996, p = 0.05), donor gender (female vs. male, Fc = 0.702, 95% CI = 0.524-0.942, p = 0.04), and donor hypertension (Fc = 0.623, 95% CI = 0.466-0.832, p= <0.01) were significantly and independently associated with SI. Moreover, donor gender (Fc = 0.512, 95% CI = 0.302-0.864, p = 0.02), donor cause of death (cerebrovascular accident vs. cardiac arrest, Fc = 2.129, 95% CI = 0.915-4.946, p = 0.09; trauma vs. cardiac arrest, Fc = 2.129, 95% CI = 1.112-7.106, p = 0.04), pancreas weight (Fc = 1.01, 95% CI = 1.001-1.019, p = 0.03), and islet equivalent (IEQ)/mg (Fc = 1.277, 95% CI = 1.088-1.510, p ≤ 0.01) were significantly and independently associated with AUC. There was no predictor significantly associated with the temporal evolution between Day 1 and Day 7 for both SI and AUC outcomes. Conclusion: This study identified donor- and isolation-related factors influencing in vitro islet secretory function. Further investigations are essential to validate the applicability of these results in clinical practice.

Statistical tools for dose individualization of mycophenolic acid and tacrolimus co-administered during the first month after renal transplantation.

AIM: To predict simultaneously the area under the concentration-time curve during one dosing interval [AUC(0,12 h)] for mycophenolic acid (MPA) and tacrolimus (TAC), when concomitantly used during the first month after transplantation, based on common blood samples. METHODS: Data were from two different sources, real patient pharmacokinetic (PK) profiles from 65 renal transplant recipients and 9000 PK profiles simulated from previously published models on MPA or TAC in the first month after transplantation. Multiple linear regression (MLR) and Bayesian estimation using optimal samples were performed to predict MPA and TAC AUC(0,12 h) based on two concentrations. RESULTS: The following models were retained: AUC(0,12 h) = 16.5 + 4.9 × C1.5 + 6.7 × C3.5 (r(2) = 0.82, rRMSE = 9%, with simulations and r(2) = 0.66, rRMSE = 24%, with observed data) and AUC(0,12 h) = 24.3 + 5.9 × C1.5 + 12.2 × C3.5 (r(2) = 0.94, rRMSE = 12.3%, with simulations r(2) = 0.74, rRMSE = 15%, with observed data) for MPA and TAC, respectively. In addition, bayesian estimators were developed including parameter values from final models and values of concentrations at 1.5 and 3.5 h after dose. Good agreement was found between predicted and reference AUC(0,12 h) values: r(2) = 0.90, rRMSE = 13% and r(2) = 0.97, rRMSE = 5% with simulations for MPA and TAC, respectively and r(2) = 0.75, rRMSE = 11% and r(2) = 0.83, rRMSE = 7% with observed data for MPA and TAC, respectively. CONCLUSION: Statistical tools were developed for simultaneous MPA and TAC therapeutic drug monitoring. They can be incorporated in computer programs for patient dose individualization.

Impact of CYP3A4*22 allele on tacrolimus pharmacokinetics in early period after renal transplantation: toward updated genotype-based dosage guidelines.

BACKGROUND: Tacrolimus (Tac) metabolism is mainly mediated by the cytochrome P450 3A (CYP3A) subfamily. Recently, it has been reported that kidney transplant recipients carrying the CYP3A4*22 decrease-of-function allele require lower Tac doses and are more at risk of Tac overexposure than CYP3A4*1/*1 patients. This effect was shown to be independent of the CYP3A5*3 allelic status. However, the pharmacokinetic (PK) parameters assessed in previous studies were limited on single time point whole blood trough concentrations (C0) during routine follow-up of the patient after transplantation. METHODS: Our study investigates the impact of the CYP3A4*22 allele on Tac PK [C0, area under the time vs concentration curve (AUC0-12h), apparent clearance (Cl/F), Cmax, and dose requirement], time to achieve target C0, and creatinine clearance (CrCl) in 96 kidney transplant recipients considering the 2 first weeks after the graft. All patients were genotyped for both the CYP3A4*22 and the CYP3A5*3 polymorphisms. RESULTS: CYP3A4*22 carriers had higher Tac C0 during the first week with significant longer exposures to C0 > 15 ng/mL. These patients showed reduced Tac Cl/F but higher dose-adjusted AUC0-12h and Cmax and were at increased risk of C0 > 20 ng/mL. These effects were independent from CYP3A5*3 genotype: clustering patients according to both CYP3A4*22 and CYP3A5*3 allelic status did increase the predictive value of the genotype to explain interindividual differences in Tac PK. During the second week after transplantation, CrCl was on average 9.5 mL/min higher for CYP3A4*22 carriers compared with CYP3A4*1/*1 patients (P = 0.007), suggesting that Tac overexposure in CYP3A4*22 carriers might provide a renal function benefit. CONCLUSIONS: Our study confirms the decreased CYP3A4 activity toward Tac for CYP3A4*22 carriers early after transplantation and provides evidence for refining genotype-based dosage by adding the CYP3A4*22 genotype information to the CYP3A5*3 allelic status.

Renal allograft implantation on prosthetic vascular grafts: short- and long-term results.

BACKGROUND: Arterial anastomosis in transplant patients with severe aortic and iliac atheromatosis is technically challenging and may jeopardize the success of the transplantation procedure. The aim of this retrospective study was to report short- and long-term results of a consecutive series of kidney transplant patients in whom the renal artery was implanted on a prosthetic vascular graft. MATERIALS AND METHODS: Medical charts and outpatient clinical records of patients who had undergone renal artery implantation on a prosthetic graft were reviewed. Data on patient characteristics, indications for transplantation, prior vascular procedures, surgical technique, and postoperative and long-term outcome were collected. RESULTS: The renal artery was implanted on a prosthetic graft in the course of 27 kidney transplantation procedures. Patients were divided into three groups according to the timing of the vascular intervention in relation to the transplantation. In group A (n = 22), the vascular prosthesis was implanted before kidney transplantation, in group B (n = 2), prosthetic iliac artery replacement and kidney transplantation were performed simultaneously, while in group C (n = 3), the vascular prosthesis was implanted after kidney transplantation. After a median follow-up of 50.5 months, one case of early arterial thrombosis was observed (3.7 %). Infectious complications occurred in two patients (7.4 %) related to mycotic pseudoaneurysms. One hematoma and one evisceration were also encountered, but no late arterial thrombosis nor stenosis were noted. Mean creatinine levels at 1 and 5 years of follow-up were 1.32 ± 0.36 and 1.27 ± 0.56 mg/dl, respectively. Five-year patient and graft survival rates were 85.2 and 74 %, respectively. CONCLUSIONS: Grafting of the renal artery to a vascular prosthesis is feasible and yields good results, despite the technical difficulties involved. We stress the importance of good teamwork.

Continuous vs. discontinuous purification of isolated human islets: functional and morphological comparison.

Background: The COBE 2991 cell processor, commonly used for pancreatic islet isolation, is no longer distributed in Europe, leading to a search for alternative purification procedures with equivalent efficacy. The aim of this study was to evaluate the efficacy of an alternative method based on the discontinuous purification of islets. Methods: The conventional isolation procedure using a standard continuous islet purification with COBE 2991 of n = 4 human pancreas was compared to n = 8 procedures using a discontinuous purification with a "bottle" method from donors of similar characteristics. Islet equivalents, purity, and dynamic glucose-stimulated insulin secretion were evaluated. Results: A similar islet yield was obtained using continuous vs. discontinuous purification methods (76,292.5 ± 40,550.44 vs. 79,625 ± 41,484.46 islet equivalents, p = 0.89). Islets from both groups had similar purity (78.75% ± 19.73% vs. 55% ± 18.16%, p = 0.08) and functionality both in terms of stimulation index (3.31 ± 0.83 vs. 5.58 ± 3.38, p = 0.22) and insulin secretion (1.26 ± 0.83 vs. 1.53 ± 1.40 mean AUC, p = 0.73). Moreover, the size of the islets was significantly larger in the discontinuous vs. continuous purification group (19.2% ± 10.3% vs. 45.4% ± 18.8% of islets less than 100 µm, p = 0.0097 and 23.7% ± 5.3% vs. 15.6% ± 5.8% of 200-250 µm islet size, p = 0.03). Conclusion: Compared to the conventional purification procedure, discontinuous purification with a bottle method shows similar results with regard to isolation yield and islet secretory function. Furthermore, this alternative technique allows for obtaining larger islets.

In situ management of late thrombosis of a renal graft vein in a patient with Cockett syndrome / Prise en charge in situ d'une thrombose tardive de la veine d'un greffon rénal chez une patiente avec un syndrome de Cockett

Late thrombosis of the renal graft vein is a rare complication that results in graft loss in the majority of cases. We describe the case of a 57-year-old female patient who had a kidney transplant 32 years ago and developed a late thrombosis of the graft vein, accompanied by extensive thrombosis in the common femoral and iliac veins. Risk factors included severe malnutrition, chronic inflammation due to an anal fistula, and Cockett syndrome. The treatment consisted of mechanical thrombectomy of the iliac vein, placement of a stent in the common iliac vein, partial thromboaspiration of the renal vein thrombus with local thrombolysis, followed by systemic anticoagulation. With this approach, renal function fully recovered without major complications.

La thrombose tardive de la veine du greffon rénal est une complication rare qui conduit à la perte du greffon dans la majorité des cas. Nous présentons le cas d'une femme de 57 ans, transplantée depuis 32 ans, qui a développé une thrombose de la veine du greffon, se manifestant par une insuffisance rénale aiguë anurique. Cette thrombose compliquait une thrombose extensive débutant dans la veine fémorale superficielle et s'étendant dans les veines fémorale commune et iliaque. La patiente présentait plusieurs facteurs de risque de thrombose veineuse, tels qu'un état de malnutrition sévère, une inflammation chronique due à une fistule anale chronique et un syndrome de Cockett. La patiente a été traitée en plusieurs étapes successives : une thrombectomie mécanique de toute la veine iliaque a d'abord été réalisée, suivie de la mise en place d'un stent dans la veine iliaque commune gauche en raison du syndrome de Cockett, puis d'une thrombo-aspiration partielle du thrombus de la veine rénale combinée à une thrombolyse locale (par urokinase) de la veine rénale via un cathéter, et enfin d'une anticoagulation systémique. Cette approche a permis une récupération complète de la fonction rénale sans complication notable. Nous rapportons cette prise en charge in situ d'une thrombose tardive de la veine d'un greffon rénal chez une patiente avec un syndrome de Cockett, ayant permis une issue favorable.

Peripheral embolism as first and only clinical symptom of a true aneurysmal degeneration of the radial artery after ligation of a radiocephalic fistula.

True aneurysmal degeneration of the inflow artery after arteriovenous fistula ligation is extremely rare. Pain is the most common symptom and surgical treatment by an autologous venous bypass is considered as the treatment of choice with good long-term results. We present a patient with peripheral embolism as first and only symptom leading to the diagnosis of a true aneurysmal degeneration of the entire left radial artery. It was discovered 5 years after the ligation of his radiocephalic fistula. As illustrated by this case, a conservative treatment by antiplatelet and anticoagulation therapy should be considered a satisfying alternative to the standard bypass surgery in patients with anatomical variations (e.g. an incomplete arterial palmar arch) since the latter include a higher risk of postoperative ischemic complications.