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See detailThe closure of arteriovenous fistula in kidney transplant recipients is associated with an acceleration of kidney function decline
WEEKERS, Laurent ULg; VANDERWECKENE, Pauline ULg; pottel, hans et al

in Nephrology Dialysis Transplantation (2016)

ABSTRACT Background. The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney ... [more ▼]

ABSTRACT Background. The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown. Methods. From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665–2028). Results. The eGFR slope was less in Group 1 (−0.081 mL/min/ month) compared with Group 0 (−0.183 mL/min/month; P = 0.03) or Group 2 (−0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (−0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P= 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient (n = 99). Conclusions. In conclusion, a significant acceleration of eGFR decline is observed over the 12 months following the closure of a functioning AVF in KTRs. [less ▲]

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See detailNon-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: omics analyses of urine and blood samples
Erpicum, Pauline ULg; HANSSEN, Oriane ULg; WEEKERS, Laurent ULg et al

in Clinical Kidney Journal (2016)

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ... [more ▼]

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene-expression profiling and omics analyses of blood and urine samples. Most imaging techniques, such as contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leucocytes may be detectable by 18F-fluorodeoxyglucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, CXCL10 and 18S RNA levels, have been identified. None of these approaches has yet been adopted in the clinical follow-up of KTRs, but standardization of analysis procedures may help assess reproducibility and comparative diagnostic yield in large, prospective, multicentre trials. [less ▲]

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See detailHome blood pressure in kidney transplant recipients (Ktr) - Validity of different schedules of self-monitoring
SAINT-REMY, Annie ULg; WEEKERS, Laurent ULg; BONVOISIN, Catherine ULg et al

in Journal of Hypertension (2016, September), 34(e supplement 2), 119

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See detailHOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (Ktr)-VALIDITY OF DIFFERENT SCHEDULES OF SELF-MONITORING
Saint-Remy, Annie ULg; WEEKERS, Laurent ULg; BONVOISIN, Catherine ULg et al

Poster (2016, June 11)

Office blood pressure (OBP) coupled with 24-h ambulatory monitoring (24-h ABPM) or home self-monitoring (HBPM) allow a more accurate assessment of BP control in treated hypertensive patients and ... [more ▼]

Office blood pressure (OBP) coupled with 24-h ambulatory monitoring (24-h ABPM) or home self-monitoring (HBPM) allow a more accurate assessment of BP control in treated hypertensive patients and identification of different phenotypes of BP. ESH/ESC guidelines (2013) recommended 7 days of home measurements (3 days at least) but that duration is questioned. The present study examined if we can reduce, and to what extent, the 7-days schedule for home measurements in treated hypertensive kidney transplant recipients (ktr) while keeping a reliable assessment of their BP status? [less ▲]

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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
Erpicum, Pauline ULg; WEEKERS, Laurent ULg; DETRY, Olivier ULg et al

Conference (2016, April 28)

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 detailHigh-urgency kidney transplantation in the Eurotransplant Kidney Allocation System: success or waste of organs? The Eurotransplant 15-year all-centre survey.
Assfalg, Volker; Huser, Norbert; van Meel, Marieke et al

in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (2016)

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 ... [more ▼]

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. [less ▲]

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See detailRecommendations for donation after circulatory death kidney transplantation in Europe.
van Heurn, L. W. Ernest; Talbot, David; Nicholson, Michael L. et al

in Transplant international : official journal of the European Society for Organ Transplantation (2016)

Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys ... [more ▼]

Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management. [less ▲]

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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 ULg; Erpicum, Pauline ULg; DETRY, Olivier ULg 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 ULg; ERPICUM, Pauline ULg; DETRY, Olivier ULg 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 ULg; DE ROOVER, Arnaud ULg 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 detailIncreased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation
WEEKERS, Laurent ULg; Ledinh, H; BONVOISIN, Catherine ULg 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 detailHome Blood Pressure in Kidney Transplant Recipients (ktr)- Validity of different schedules of self-monitoring
Saint-Remy, Annie ULg; WEEKERS, Laurent ULg; BONVOISIN, Catherine ULg et al

Conference (2015, October 24)

HOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (KTR)-Validity of different schedules of self-monitoring A. Saint-Remy, L. Weekers, C. Bonvoisin, P. Xhignesse, B.Dubois, JM. Krzesinski NEPHROLOGY ... [more ▼]

HOME BLOOD PRESSURE IN KIDNEY TRANSPLANT RECIPIENTS (KTR)-Validity of different schedules of self-monitoring A. Saint-Remy, L. Weekers, C. Bonvoisin, P. Xhignesse, B.Dubois, JM. Krzesinski NEPHROLOGY - CHU LIEGE AIM: Office blood pressure (OBP), 24-h ambulatory monitoring (ABPM) and home self- monitoring (HBP) allow assessing BP control in treated HT patients. For HBP, ESH guidelines recommend 7 days of measurements but that duration is questioned. The present study analyzed the agreement between daytime ABP and different schedules for HBP in 70 treated hypertensive KTR. METHOD: BP control defined by OBP <140/90 and daytime ABP or HBP <135/85 mmHg was tested in 70 KTR (mean age 56 ± 11 y; mean graft survival 7 ± 6.6 y). OBP and HBP were measured with an Omron M6 and 24-h ABPM with a Spacelabs 90207. HBP was measured on consecutive days (2 times in morning and 2 times at evening/day), the first day was discarded for the mean calculation. Agreement between daytime and HBP was studied when HBP was measured during 7, 5 or 3 days. RESULTS: BP was uncontrolled in 50% of the KTR based on OBP, in 61 % according to daytime ABP and even in 64 % with HBP. Sensitivity (Se) testing agreement between daytime ABP and HBP decreased progressively when number of days was shortened: the highest Se was observed for a 7 days duration with 1st day discarded (86 %). Specificity (Sp) fluctuated around 70 % and was the highest for a 5 (73 %) and 3 days schedule. However the 5 days schedule had higher Se (83 %) than the 3 days. Proportions of KTR correctly classified according to daytime ABP were 79 %, 79 % and 78 % with the 7, 5 or 3 days schedule, respectively. CONCLUSIONS: HBP, easier and less restricting method than 24h ABPM, is a good alternative to daytime ABPM as nearly 80 % of treated KTR were similarly classified. HBP recording period can be shortened to 5 days according to Se and Sp. A 3 days schedule seems more risky reducing the chance to identify masked HT due to a decreased drug adherence. [less ▲]

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See detail18FDG-PET/CT IMAGING IN SUSPECTED ACUTE RENAL ALLOGRAFT REJECTION
LOVINFOSSE, Pierre ULg; WEEKERS, Laurent ULg; BOVY, Christophe ULg et al

Conference (2015, September 13)

The diagnosis procedure for kidney transplant recipients (KTR) with suspected acute rejection (AR) relies on needle biopsy. Noninvasive tests to predict nonrejection would be preferable. AR is associated ... [more ▼]

The diagnosis procedure for kidney transplant recipients (KTR) with suspected acute rejection (AR) relies on needle biopsy. Noninvasive tests to predict nonrejection would be preferable. AR is associated with a recruitment of activated leukocytes into the transplant, which are characterized by a high metabolic activity and an increased uptake of glucose analog, Fluoro-deoxyglucose ( FDG). Thus, FDG-Positron emission tomography coupled with computed tomography (PET/CT) may help noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 FDGPET/ CT in 31 adult KTR with suspected renal AR who underwent a biopsy. Biopsies were categorized as “normal”, “borderline”, “AR” or “others” according to Banff classification. PET/CT imaging was performed within 201 ± 18 minutes after i.v. administration of 3.2 ± 0.2 MBq/kg of FDG, before any modification of immunosuppression. The mean standard uptake values (SUV) of both upper and lower renal poles were measured, with no threshold activity. Biopsies were diagnosed as “normal”, “borderline”, “AR” or “others” in 8, 10, 8 and 6 (including 3 polyoma-BK nephropathies) cases. Mean SUV respectively reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, 2.2 ± 1.2 in each category. Mean SUV of biopsy-proven AR was significantly higher than “normal” cases (p<0.01). No difference was found between “normal” vs. “borderline”, or between “AR” vs. “others” histopathology. Still, a positive correlation between mean SUV and acute composite (g+i+t+v+ptc) Banff score was found, with a coefficient of 0.70 (p<0.001). Sensitivity and specificity of FDG-PET/CT in detecting pathological biospies were respectively 92.3% and 36.8%, with a mean SUV threshold at 1.4. FDG-PET/CT imaging may help discriminate nonrejection, thereby avoiding unnecessary transplant biopsy in KTR with suspected AR. [less ▲]

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

in American Journal of Transplantation (2015, May), 15(suppl 3),

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See detailActivation of the calcium-sensing receptor before renal ischemia/reperfusion exacerbates kidney injury
WEEKERS, Laurent ULg; De Tullio, Pascal ULg; BOVY, Christophe ULg et al

in American Journal of Translational Research (2015), 7(1), 128-138

Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R) favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal I/R is unknown. We investigated the impact ... [more ▼]

Activation of the calcium-sensing receptor (CaSR) by ischemia/reperfusion (I/R) favours apoptosis in cardiomyocytes, hepatocytes and neurons. Its role in renal I/R is unknown. We investigated the impact of pharmacological preactivation of the CaSR on kidney structure and function in a murine model of bilateral renal 30-min ischemia and 48-hour reperfusion, and in a 6-year cohort of kidney transplant recipients (KTR). C57BL/6J mice were administered daily with CaSR agonist, R-568, or with vehicle for 48 hours. Evaluation of serum urea and creatinine levels, renal histology and urine metabolome by nuclear magnetic resonance showed that R-568 was not nephrotoxic per se. Following I/R, serum urea and creatinine levels increased higher in R-568-treated animals than in controls. Jablonski’s score was significantly greater in R-568-treated kidneys, which showed a higher rate of cell proliferation and apoptosis in comparison to controls. Next, we retrospectively identified 36 patients (10.7% of our cohort) who were treated by CaSR agonist, cinacalcet, at the time of kidney transplantation (KTx). After matching these to 61 KTR upon type of donor, cold ischemic time, residual diuresis, and donor age, we observed that delayed graft function, i.e. need for dialysis in the first week after KTx, occurred in 42 and 23% of cinacalcet-treated and control groups, respectively (p≤0.05). These data suggest that pharmacological preactivation of the CaSR before renal I/R exacerbates kidney injury. [less ▲]

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See detailCellules stromales mésenchymateuses et transplantation d'organes
DETRY, Olivier ULg; JOURET, François ULg; VANDERMEULEN, Morgan ULg et al

in Revue Médicale de Liège (2014), 69

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and ... [more ▼]

Mesenchymal stromal cells (MSC) are multipotent and self-renewing cells. MSC are studied for their in vivo and in vitro immunomodulatory effects, in the prevention or the treatment of ischemic injury, and for their potential properties of tissue or organ reconstruction. Over the last few years, the potential role of MSC in organ transplantation has been studied both in vitro and in vivo, and their properties make them an ideal potential cell therapy after solid organ transplantation. A prospective, controlled, phase 1-2 study has been initiated at the CHU of Liege, Belgium. This study assesses the potential risks and benefits of MSC infusion after liver or kidney transplantation. Even if the preliminary results of this study look promising, solely a prospective, randomized, large scale, phase 3 study will allow the clinical confirmation of the theoretical benefits of MSC in solid organ transplantation. [less ▲]

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See detailLa maladie rénale chronique (MRC)
Krzesinski, Jean-Marie ULg; moonen, martial; WEEKERS, Laurent ULg

Scientific conference (2014, October 17)

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