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See detailSurgical factors and not donor type per se are risk factors for acute kidney injury after liver transplantation
MEURISSE, Nicolas ULiege; Smet, Heloise ULiege; LEDOUX, Didier ULiege et al

in Transplant International (2017, September), 30(S2), 106-107298

Background: Because Liver Transplantation (LT) using DCD has been shown to be risk factor for Acute Kidney Injury (AKI), we reviewed results at our center. Patients and Methods: AKI was defined as ... [more ▼]

Background: Because Liver Transplantation (LT) using DCD has been shown to be risk factor for Acute Kidney Injury (AKI), we reviewed results at our center. Patients and Methods: AKI was defined as decrease >50% eGFR (CKD- EPI) within 48 h postreperfusion (RIFLE). 106 first LT-only [63 DBD (59%) & 43 DCD (41%)] without pre-existing renal dysfunction (eGFR>60 ml/min/1,73 m2, no renal replacement therapy) were performed from 2012 to 2016. Incidence/ risk factors for AKI were assessed. Data: mean (IQR). Results: Incidence of AKI was 33% (35/106). AKI-patients were more hospitalized before LT [9/16 (56%) vs 26/89 (29%), p < 0.01], with higher labMELD [16 (10–23) vs 12 (8–16), p = 0.01]. Donor type [11/43 DCD (25%) vs 24/63 DBD (39%), p = 0.16], donor hepatectomy time [38 min (26–50) vs 35 (25–42), p = 0.37], cold ischemic time [6 h (4.1–7.6) vs 5.1 (3.4–6.4), p = 0.21], time for anastomosis [44 min (35–49) vs 42 (38–48), p = 0.53], postreperfusion syndrome [19/46 (42%) vs 27/46 (58%), p = 0.07] were similar between AKI & non-AKI groups. AKI was more frequent if lungs were procured first in the donor [23/48 (48%) vs 11/56 (19%), p < 0.01]. Recipient surgery was longer in the AKI group [5.2 h (3.9–6.3) vs 4.3 (3.4–4.8), p < 0.01]. AKI was more frequent if platelets were transfused during LT [19/42 (56%) vs 15/59 (44%), p = 0.03]. Blood volume administrated from the cellsaver was larger in the AKI-patients [834 ml (300–750) vs 408 (0–550), p = 0.03]. AKI-patients have a higher peak AST [1235 U/L (310–1858) vs 812 (429–978), p = 0.04]. Haemoglobin [8.8 g/dl (7.4–9.9) vs 10 (8.5–11.7)] & platelets [69x103 (50 9 103–87 9 103) vs 89 9 103 (50 9 103–118 9 103)] at day 1 postreperfusion were significantly lower if AKI occurred. After multivariable analysis, thoracic procurement before liver [OR 5.75 (1.76–18.77), p = 0.004] & recipient surgery duration [OR 1.64 (1.15–2.32), p = 0.006] were only risk factors for AKI. Conclusion: Rapid donor/recipient surgery and not donor type are key factors to prevent AKI-post-LT. [less ▲]

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See detailDO MESENCHYMAL STROMAL CELLS PROMOTE HLA SPECIFIC ANTIBODIES FORMATION AFTER INFUSION IN LIVER TRANSPLANT RECIPIENTS?
VANDERMEULEN, Morgan ULiege; MAGGIPINTO, Gianni ULiege; JOURET, François ULiege et al

in Transplant International (2017, September), 30(S2), 548051

Background: Mesenchymal stromal cells (MSC) immunogenicity is debated. We recently published a prospective, controlled, phase I study evaluating a single administration of third-party MSC in 10 liver ... [more ▼]

Background: Mesenchymal stromal cells (MSC) immunogenicity is debated. We recently published a prospective, controlled, phase I study evaluating a single administration of third-party MSC in 10 liver transplant recipients (LTR). Here, we focus on the development of antibodies (Ab) against MSC-donor HLA (MSCDSA) in LTR following MSC infusion. Methods: Ten LTR under standard immunosuppression received 3rd-party unrelated MSC on postoperative day 3, and were prospectively compared to 10 control LTR. Recipients and donor of either liver or MSC were genotyped for HLA A/B/C/DR/DQ. Recipients were tested for HLA Ab before and 1, 3 and 6 months after transplant by Luminex". Ab were considered as positive in case of MFI >1500 and in accordance with the manufacturer’s recommendations. Results: In MSC-treated group, 2 patients showed pre-transplant MSCDSA. During follow-up, MSCDSA were detected in 6 additional patients who had received multiple red blood cell allo-transfusions before and/or rapidly after transplant. These patients also developed Ab against various MSC-unrelatedHLA. Two patients did not develop any MSCDSA throughout the follow-up, and one of them did not receive any allo-transfusion. MFI of detected MSCDSA were not significantly different from MFI of other detected HLA Ab. In control group, 3 patients were sensitized pre-transplant, and 6 patients developed de novo multiple HLA Ab. Four of these had received multiple allo-transfusions. Conclusion: In the large pool of HLA Ab identified in LTR post transplant, the detection of MSCDSA is most likely caused by allo-transfusions rather than related to MSC infusion. Further studies are required to confirm that MSC are “immune privileged”. [less ▲]

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See detailAdministration of mesenchymal stromal cells before renal ischemia/reperfusion attenuates kidney injury and modulates renal lipid metabolism in rats
ERPICUM, Pauline ULiege; Rowart, Pascal ULiege; POMA, Laurence ULiege et al

in Transplant International (2017, September), 30(S2), 9004

Background: Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodents. The mecha- nisms of such nephroprotection remain unclear. Materials and ... [more ▼]

Background: Mesenchymal stromal cells (MSC) have been demonstrated to attenuate renal ischemia/reperfusion (I/R) damage in rodents. The mecha- nisms of such nephroprotection remain unclear. Materials and Methods: Male Lewis rats aged of 8–10 weeks received tail i.v injection of 1.5x106 MSC in 1 mL saline (MSCD-7, n = 11) or saline alone (SD- 7, n = 6) 7 days before renal I/R. Left renal ischemia (by clamping the renal pedicle) lasted 45 min. Right nephrectomy was simultaneously performed. Blood sample was collected from inferior vena cava 48 h post reperfusion. Renal function was assessed by measuring serum creatinine (SCr) levels. Expressions of inflammatory and apoptotic markers by real-time (RT)-qPCR were comparatively quantified. High-throughput RNA sequencing was applied to MSCD-7 vs. SD-7 non-ischemic right kidneys. Relevant pathways were detected using an Over-Representation Analysis with WebGestalt, and confirmed by RT-qPCR. Results: Scr levels reached 1.4 ` 0.7 vs. 2.4 ` 0.8 mg/dL in MSCD-7 vs. SD-7 group (p < 0.05). MSC infusion significantly reduced mRNA expression of Casp3, Hsp 70, Kim-1, Mcp-1 and Il-6 and increased mRNA expression of Bcl compared to saline. Among 25 908 genes, 748 were identified as significantly differentially expressed (False Discovery Rate (FDR), <0.05) between MSCD-7 and SD-7 non-ischemic kidneys. Among the most affected metabolic pathways, renal lipid metabolism was significantly altered, with down-regulation of fatty acid biosynthesis and an up-regulation of PPARa pathway in MSCD-7 vs. SD-7 groups. By immunoblotting, PPARa and phosphorylated-PPARa were significantly increased in MSCD-7 vs. SD-7 kidneys, in both non-ischemic and ischemic conditions. Moreover, levels of malondialdehyde-derived lipid peroxidation products were decreased in MSCD-7 ischemic kidneys in comparison to SD-7 ischemic kidneys. Conclusion: MSC infusion at day 7 prior injury critically impacts renal lipid metabolism, which may condition kidney parenchyma against I/R. [less ▲]

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See detailUNE INJECTION UNIQUE DE CELLULES STROMALES MESENCHYMATEUSES AU JOUR 3 APRES GREFFE HEPATIQUE EST INSUFFISANTE POUR INDUIRE UNE TOLERANCE OPERATIONNELLE
DETRY, Olivier ULiege; VANDERMEULEN, Morgan ULiege; DELBOUILLE, Marie-Hélène ULiege et al

in Transplant International (2017, January), 30(suppl 1), 812

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis ... [more ▼]

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis of possible induction of operative tolerance by third-party MSC in liver transplant (LT) recipients. Methods: 10 stable and low-risk LT recipients under standard immunosup- pression (Tac-MMF- low dose steroids) received 1.5–3 9 106/kg third-party MSCs on post-operative day 3 ` 2. By protocol, progressive weaning of immunosuppression was attempted in patients who did not develop rejection and had normal graft function and month-6 graft biopsy. Tacrolimus was progressively tapered from day 180 to be discontinued by day 270. After day- 270 graft biopsy, MMF was progressively tapered and definitely discontinued by day 365 in the absence of rejection. Results: One patient from the MSC group was excluded from immunosup- pression withdrawal attempt due to HCC recurrence, and the 9 others met the necessary criteria. In one patient, tacrolimus and MMF withdrawal was performed without rejection. In two patients, MMF monotherapy was achieved at month 9, but graft rejection occurred during MMF withdrawal and was successfully treated by tacrolimus reintroduction. In 6 patients, the transam- inases significantly increased during tacrolimus withdrawal. In these cases, withdrawal was cancelled and liver tests normalised after increase of the tacrolimus dose. No graft was lost due to the withdrawal attempt. Conclusion: A single post transplant MSC injection is not sufficient to induce operative tolerance after LT. [less ▲]

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See detailUne série consécutive de 125 greffes hépatiques à partir de donneurs cadavériques en mort circulatoire
DETRY, Olivier ULiege; MEURISSE, Nicolas ULiege; HANS, Marie-France ULiege et al

in Transplant International (2017, January), 30(Suppl 1), 2481

Introduction: Donation after circulatory death (DCD) has been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of graft loss and ... [more ▼]

Introduction: Donation after circulatory death (DCD) has been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of graft loss and retransplantation. The authors retrospectively reviewed a single centre experience with controlled DCD-LT in a 14-year period. Patients and Methods: 125 DCD-LT were consecutively performed between 2003 and 2016. All donation and procurement procedures were performed as controlled DCD in operative rooms. Data are presented as median (ranges). Median donor age was 56 years (16–84). Most grafts were flushed with HTK solution in the first part of experience, and more recently with IGL1. Allocation was centre-based. Median follow-up was 52 (1–164) months. No patient was lost to follow-up. Results: Median total DCD warm ischemia was 19 min (9–39). Median cold ischemia was 238 min (105–576). Patient survivals were 90.2%, 77.5% and 74.5 % at 1.3 and 5 years, respectively. Graft survivals were 87.7%, 76.3% and 73.2% at 1.3 and 5 years, respectively. Biliary complications included anas- tomotic strictures and extrahepatic main bile duct ischemic obstruction, that were managed either by endoscopy or hepatico-jejunostomy. No PNF was observed in this series and one graft was lost due to ischemic cholangiopathy. Discussion: In this series, DCD LT appears to provide results similar to classical LT. Short cold ischemia and recipient selection with low MELD score may be the keys to good results in DCD LT, in terms of graft survival and avoidance of ischemic cholangiopathy. [less ▲]

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See detail"Acute kidney dysfunction with no rejection (ADNR)" is associated with poor outcomes in kidney transplant recipients
PAQUOT, Francois ULiege; Pottel, Hans; BONVOISIN, Catherine ULiege et al

in Transplant International (2017), 30((Suppl. 2)), 558

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See detailadministration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up
WEEKERS, Laurent ULiege; Erpicum, Pauline ULiege; DETRY, Olivier ULiege et al

in Transplant International (2016), 29(Suppl 2), 13-6

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx ... [more ▼]

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx. Methods. On postoperative day 3 (D3), third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recipients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. In parallel, 7 comparable KTx recipients were included as controls. Written informed consent was obtained from all participants. Results. No hemodynamic or immune-allergic side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Four MSC patients presented with CMV reactivation within 165 ± 96 days post KTx, whereas 3 controls had positive polyoma-BK viremia within 92 ± 4d post KTx. Three MSC patients were affected by pneumonia within 269 ± 98d post KTx, whereas 3 controls had urinary infection within 48 ± 43d post KTx. No MSC engraftment syndrome was observed. At D14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 43.1 ± 17.8 and 53.9 ± 13.4 ml/min, respectively (p, 0.25). At 3-month protocol biopsy, no rejection was evidenced in MSC or control patients. Later on, 1 acute rejection was diagnosed at D330 in 1 MSC patient. No biopsy-proven AR was noted in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches. Conclusions. MSC infusion was safe in all patients except one. Incidence of opportunist and non-opportunist infections was similar in both MSC and control groups. No MSC engraftment syndrome was documented. No difference in eGFR was found at 1 year post KTx. Putative immunization against MSC was observed in 3 patients. [less ▲]

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See detailThird-party mesenchymal stem cell infusion in kidney transplant recipient: 6-month safety interim analysis
WEEKERS, Laurent ULiege; ERPICUM, Pauline ULiege; DETRY, Olivier ULiege et al

in Transplant International (2015, November), 28(S4), 223-224278

Background: Mesenchymal stromal cell (MSC) have immunomodulating properties and could be used as immunosuppressive agents. We report the 6- month safety results for the 5 first patients treated with MSC ... [more ▼]

Background: Mesenchymal stromal cell (MSC) have immunomodulating properties and could be used as immunosuppressive agents. We report the 6- month safety results for the 5 first patients treated with MSC after kidney transplantation (KTx). Here, we address 3 specific safety issues: immunization against MSC and engraftment syndrome defined as acute graft dysfunction not related to rejection and over-immunosuppression. Patients and method: MSC production was carried out locally. MSC were not matched with kidney recipients’ HLA. Included patients were non-immunized, first transplant recipients from deceased donors. MSC (1.5–3.0 9 106/kg) infusion was planned 3 to 5 days post KTx. Patients with cardiovascular instability post KTx were excluded. All patients were treated with Basiliximab induction, Tacrolimus, Mycophenolate Mofetil and Steroid. We prospectively screened for anti-HLA antibodies at month 1, 3 and 6. Informed consent was obtained from all participants. The local ethical committee approved the protocol. Results: Collectively there were 23/50 and 29/50 HLA mismatches (MM) with kidney and MSC donor respectively, out of which 5 were shared MM. One patient developed de novo DSA, 2 patients anti-HLA antibodies against shared kidney/MSC MM and 1 patient developed 2 specific antibodies against MSC (MSCSA) at month 6. All antibodies were anti HLA class I except for 1. We did not observe any “engraftment” syndrome. Three patients experienced non- severe opportunistic infections: 1 CMV reactivation and 2 polyoma-BK virus viremia.Conclusion: We did not observe any strong safety signal. We did however observe some degree of immunization in 3 patients: 2 developed antibodies against shared kidney/MSC donor HLA MM and 1 MSCSA. [less ▲]

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See detailComparable transplant outcomes between DBD and DCD kidney grafts up to 5 years post-transplant: single centre experience
Ledinh, H; DETRY, Olivier ULiege; DE ROOVER, Arnaud ULiege et al

in Transplant International (2015, November), 28(S4), 193-194188

Introduction: This study aimed to determine the most recent results of kidney transplantation (KT) from donation after brain death (DBD) and circulatory death (DCD). Primary endpoints were graft and ... [more ▼]

Introduction: This study aimed to determine the most recent results of kidney transplantation (KT) from donation after brain death (DBD) and circulatory death (DCD). Primary endpoints were graft and patient survival, and graft function. Acute rejection and post-operative complications were assessed as secondary endpoints. Patient and Methods: This retrospective mono-center review consisted of 226 DBD- and 104 DCD-KT between 2008 and 2014. Results: Graft survival was comparable between two groups (95.1 vs. 91.1% at 1 year, 92.8 vs. 91.1% at 3 years and 89.2 vs. 91.1% at 5 years). 46% and 40% of graft loss were attributed to patient death with a functioning graft and rejection. Patient survival was comparable between 2 groups (97.8 vs. 95.1% at 1 year, 94.1 vs. 91.2% at 3 years, and 89.6 vs. 82.3% at five years). Etiology of patient death included cardiac arrest (16.7%), infection (16.7%), cancer (13.3%), and unknown cause (46.7%). Delayed graft function occurred in 14.6% of DBD- and 30.8% of DCD-KT (p = 0.001). Primary non function was encountered in 2.6% DBD- and 4.8% DCD-KT (p = ns). Graft function was worse in DCD than DBD up to 3 months post-transplant (p = 0.034), however, no difference existed afterwards. Biopsy-proven acute rejection was found in 12.8% and 13.5% of DBD- and DCD-KT during an average 3 months post- transplant (p = ns). This rate was 7.1% vs. 8.9% on surveillance biopsy performed between 3 and 6 months post-transplant (p = ns). Post-operativecomplication rate was comparable between 2 groups, concerning patient death, reoperation, transfusion, perirenal hematoma, macroscopic hematuria, urinary obstruction, wound problem, and infection. Nevertheless, contamination of preservation solution occurred more commonly in DCD than DBD (0.4% vs. 3.8%, p = 0.036). Conclusions: Despite worse early graft function, DCD-KT was not inferior to that originating from DBD up to 5 years post-transplant, therefore deserves to be used. [less ▲]

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See detailInfusion of third-party mesenchymal stream cells after liver transplantation: a phase-1, open-label, clinical study
DETRY, Olivier ULiege; VANDERMEULEN, Morgan ULiege; DELBOUILLE, Marie-Hélène ULiege et al

in Transplant International (2015, November), 28(S4), 1027

Background: Mesenchymal stromal cells (MSC) are multipotent bone mar- row progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are multipotent bone mar- row progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed to be the first evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled phase-1 study. Methods: 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5–3 9 106/kg third party MSC on post-operative day 3 ` 2. These patients were prospectively compared to a group of 10 control liver recipients. Primary endpoints were MSC infusion toxicity, and incidence of cancer and opportunistic infections at month 6. Secondary endpoints were patient and graft survivals and rejection at month 6, as well as the effects of MSC on recipients’ immune function and on immunohistology of at month 6 graft biopsies. Results: No MSC infusional toxicity was observed. Both groups were comparable in terms of donor and recipient characteristics. There was no difference in primary end-points between control and MSC groups. No patient developed de novo cancer. There was no statistical difference in patient and graft survivals or in rejection rates. There was no graft rejection in the MSC group. Month-6 graft biopsies were not different according to Banff and fibrosis scores. Discussion: This phase 1 study showed excellent tolerability and safety of a single infusion of third-party MSC after liver transplantation. There were no graft safety issues and no excess of immunosuppression after MSC injection. Further analyses of consequences of MSC injection on the immune profile are needed. The possibility of avoiding calcineurin-inhibitors with repeated MSC injections as main immunosuppressive therapy and/of tolerance induction by MSC infusion should be investigated by further studies. This study is in part supported by an ESOT Senior Clinical Research Grant and by the University of Liege. [less ▲]

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See detailImpact of timing administration of mesenchymal stromal cells on serum creatinine following renal ischemia/ reperfusion in rats
ERPICUM, Pauline ULiege; Rowart, Pascal ULiege; POMA, Laurence ULiege et al

in Transplant International (2015, November), 28(S4), 1129

Experimental models of renal ischemia/reperfusion (I/R) have suggested protective effects of mesenchymal stromal cells (MSC) therapy. Still, param- eters of MSC injection, including volume, route and ... [more ▼]

Experimental models of renal ischemia/reperfusion (I/R) have suggested protective effects of mesenchymal stromal cells (MSC) therapy. Still, param- eters of MSC injection, including volume, route and timing of cell administration, remain largely debated. Particularly, MSC infusion in mouse has been shown to be beneficial “a priori” but deleterious “a posteriori” of renal I/R injury. In order to further investigate the influence of the timing of MSC administration, we used 10-week-old Lewis rats categorized in 4 groups. Groups 1 (MSC D-7, n = 10) and 2 (MSC D + 1, n = 7) received caudal i.v. injection of MSC (1.5 9 106 in 1 ml of saline) 7 days before or 1 day after renal I/R, respectively. Control groups 3 (saline D-7, n = 6) and 4 (saline D + 1, n = 6) received equal volume of saline at similar time points. Left renal ischemia (by clamping of the renal pedicle) lasted 45 min. Right nephrectomy was simultaneously performed. Blood sample was collected from inferior vena cava at 48 h post reperfusion. MSC phenotype was confirmed by FACS analysis. In groups 1 and 3, serum creatinine (SCr) reached 1.4 ` 0.7 versus 2.4 ` 0.8 mg/dl, respectively (p < 0.05). In groups 2 and 4, SCr was 4.9 ` 0.7 versus 3.3 ` 0.9 mg/dl, respectively (p < 0.001). Furthermore, SCr levels were statistically worse when MSC were administered after renal I/R in comparison to a priori infusion (p < 0.0001). In conclusion, MSC administration 7 days prior to renal I/R attenuates kidney injury in comparison to (i) saline infusion or (ii) MSC infusion 1 day after renal I/R. Conversely, on the basis of SCr levels, MSC therapy performed after renal I/R worsens kidney injury in rats. [less ▲]

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See detailIncreased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation
WEEKERS, Laurent ULiege; Ledinh, H; BONVOISIN, Catherine ULiege et al

in Transplant International (2015, November), 28(S4), 49118

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few ... [more ▼]

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function. [less ▲]

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See detailA consecutive series of 100 controlled DCD liver transplantation
DETRY, Olivier ULiege; DE ROOVER, Arnaud ULiege; Ledinh, H et al

in Transplant International (2015, November), 28(S4), 109296

Introduction: Donation after circulatory death (DCD) have been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of graft loss and ... [more ▼]

Introduction: Donation after circulatory death (DCD) have been proposed to partially overcome the organ donor shortage. DCD-LT remains controversial, with reported increased risk of graft loss and retransplantation. The authors retrospectively reviewed a single centre experience with controlled DCD-LT in a 12-year period. Patients and Methods: 100 DCD-LT were consecutively performed between 2003 and 2014. All donation and procurement procedures were performed as controlled DCD in operative rooms. Data are presented as median (ranges). Median donor age was 57 years (16–83). Median DRI was 2.16 (1.4–3.4). Most grafts were flushed with HTK solution. Allocation was centre-based. Median recipient MELD score at LT was 15 (7–40). Mean follow-up was 35 months. No patient was lost to follow-up. Results: Median total DCD warm ischemia was 19 min (10–39). Median cold ischemia was 235 min (113–576). Median peak AST was 1132 U/l (282– 21 928). Median peak bilirubin was 28 mg/dL. Patient survivals were 90.7%, 75.5% and 70.7% at 1.3 and 5 years, respectively. Graft survivals were 88.7%, 72.1% and 67.1% at 1.3 and 5 years, respectively. Biliary complications included mainly anastomotic strictures and extrahepatic main bile duct ischemic obstruction, that were managed either by endoscopy or hepatico- jejunostomy. No PNF or graft loss due to ischemic cholangiopathy was observed in this series. Discussion: In this series, DCD LT appears to provide results similar to classical LT. Short cold ischemia and recipient selection with low MELD score may be the keys to good results in DCD LT, in terms of graft survival and avoidance of ischemic cholangiopathy. If symptomatic ischemic cholangiopa- thy is diagnosed, adequate management with endoscopy and surgical hepaticojejunostomy may avoid graft loss and retransplantation. [less ▲]

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See detailTransfusion needs during liver transplantation at the chu of liege (belgium): characteristics and preoperative predictive factors
PAGE, Isaline ULiege; HANS, Grégory ULiege; DETRY, Olivier ULiege et al

in Transplant International (2015, November), 28(S4), 461272

Introduction: Liver transplantation (LT) can result in significant bleeding requiring transfusion of allogenic blood products, which potentially leads to postoperative morbidity and mortality (1). This ... [more ▼]

Introduction: Liver transplantation (LT) can result in significant bleeding requiring transfusion of allogenic blood products, which potentially leads to postoperative morbidity and mortality (1). This study aimed to determine transfusion needs during LT in our institution and its preoperative predictive factors. Material and Methods: Two hundred LT performed at the CHU Liege between 2006 and 2012 were respectively reviewed (age = 55 ` 11 yo, BMI = 25.5 ` 4.4 kg/m2, F/M = 45/155, MELD score = 19 ` 10). Transfu- sion needs of the different blood products during POD 0, and POD 0–7 were recorded. Parameters associated with the transfusion of more than 2 units of RBC (p ≤ 0.1) were identified using the Kruskal Wallis and chi square tests (table 1). These parameters were then placed into a backward stepwise logistic regression model for the transfusion of more than two units of RBC at POD 0. A p value threshold ≥0.1 was used for leaving the model. Results: Transfusion needs were: RBC = 2[0–4], FFP = 4[2–7], PLT = 1[0– 1] during POD 0; and RBC = 3[0–6], FFP = 6[3–10], PLT = 1[0–2] during POD 0–7. Preoperative factors independently associated with the transfusion of more than two units of RBC were preop Hb (0.6 [0.46–0.79], p < 0.001) and MELD score (1.13 [1.06–1.20], p < 0.001). Discussion: These results suggest that preop Hb and MELD score are associated with blood requirements during LT. [less ▲]

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See detailOrgan donation after euthanasia on specific patients' request in Belgium
Ysebaert, D; DETRY, Olivier ULiege; Verfaillie, G et al

in Transplant International (2015, November), 28(S4), 114313

Euthanasia is since 2002 legalized in Belgium for adults under strict conditions. The patient must be in a medically futile condition, of constant and unbearable physical or mental suffering that cannot ... [more ▼]

Euthanasia is since 2002 legalized in Belgium for adults under strict conditions. The patient must be in a medically futile condition, of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness. This implies that also non-terminal not-cancer patients can request for euthanasia for instance in case of debilitating neurological disorder. From 2005 till 2015 more than 25 patients, suffering from diverse neuropsychiatric diseases, got their request for euthanasia granted, and subsequently asked spontaneously for the possibility of organ donation. The involved physicians, the transplant teams and the Institutional Ethics Commit- tees, had the well-discussed opinion that this strong request for organ donation after euthanasia could not be denied. A clear separation between the euthanasia request, the euthanasia procedure and the organ procurement procedure was judged necessary. After extensive preparation, finally, in Belgium, 17 patients got their wish for organ donation after euthanasia fulfilled, in several academic or non-academic hospitals and in different regions. Several requests and preparations were started for other patients but ultimately did not lead to organ donation due to patients’ personal choices or logistically reasons. The euthanasia procedure was carried out by three physicians involved in the euthanasia granting. After clinical diagnosis of cardiac death, the procurement team came in and performed the organ procurement similar as in a DCD type III procedure. Almost always, liver, two kidneys and sometimes lungs and pancreatic islets were successfully recovered and transplanted, after allocation by Eurotransplant. The possibility of organ donation after their euthanasia provides a very much improved self-image of these patients, and adds something really positive to the unfortunate end-of-life of these patients. [less ▲]

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See detailEUROPEANELITA ELTRE MULTICENTER SURVEY ON THE MANAGEMENT OF BILE DUCT DURING LIVER PROCUREMENT,PRESERVATION AND TRANSPLANTATION
MEURISSE, Nicolas ULiege; Monbaliu, Diethard; Muiesan, Paolo et al

in Transplant International (2015)

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See detailPrognostic value of (18)F-FDG PET/CT in liver transplantation for hepatocarcinoma.
MEURISSE, Nicolas ULiege; DETRY, Olivier ULiege; Govaerts, L et al

in Transplant International (2014, September), 27(S2), 18-17

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See detailCinacalcet treatment at the time of transplantation is associated with a significant risk of delayed graft function in kidney transplant recipients
Jouret, François ULiege; WEEKERS, Laurent ULiege; GROSCH, Stéphanie ULiege et al

in Transplant International (2014, May), 27(S1), 167

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious ... [more ▼]

The calcium-sensing receptor (CaSR) has been implicated in the ischemia/ reperfusion (I/R) cascade in heart, liver and brain. Renal I/R occurs at the time of transplantation (Tx), with a deleterious impact on early graft function. Here, we retrospectively investigated if the use of cinacalcet, a CaSR agonist, in kidney transplant recipients (KTR) influences early graft recovery. All KTR from 2007 to 2012 in our Academic Hospital were prospectively included in a database. Patients actively treated with cinacalcet on the day of Tx were retrospectively identified from this database and matched with controls on (i) type of donor (living [LD], deceased after brain or circulatory death [DCD]); (ii) cold ischemic time (CIT) ` 1 h; (iii) residual diuresis (` 500 ml); and (iv) donor age (` 5 years). Delayed graft function (DGF) was defined as dialysis requirement after Tx. Baseline characteristics were compared between groups with student’s t-test or Chi-2 as appropriate. The endpoint was the percentage of DGF in both groups. Among 337 KTR, 36 (10.7%) were treated with cinacalcet at Tx. Control group included 61 patients. Characteristics of patients and donors are summarized in the table. DGF occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p = 0.05). These retro- spective observations suggest that CaSR activation at the time of Tx impairs early graft recovery. [less ▲]

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