References of "JOURET, François"
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See detailThe use of mesenchymal stromal cells in solid organ transplantation
GREGOIRE, Céline ULg; DETRY, Olivier ULg; Jouret, François ULg et al

in The Biology and Therapeutic Applications of Mesenchymal Cells (in press)

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See detailLa polykystose rénale autosomique dominante : comment et pourquoi identifier les patients "rapidement progresseurs" vers l'insuffisance rénale terminale?
bodson, aurélie; MEUNIER, Paul ULg; Krzesinski, Jean-Marie ULg et al

in Revue Médicale de Liège (2016), 71(4), 184-192

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients ... [more ▼]

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients with ADPKD will develop, sooner or later, end-stage renal disease (ESRD). The morbidity and mortality associated with ESRD prompt physicians to identify early ADPKD patients considered as «rapid progressors», who have the greatest risk to rapidly develop ESRD. The rate of progression can be assessed by clinical - especially with the «predicting renal outcome in polycystic kidney disease score» (PROPKD-Score) -, biological (a decline of the glomerular filtration rate (GFR) of 4,4 - 5,9 ml/min/year and/or the doubling of serum creatinine within a 36-month period), or radiological criteria (total kidney volume (TKV) adjusted for the size > 600 cc/m and/or TKV annual growth rate > 5 %). Nowadays, there is no curative treatment for ADPKD. However, vasopressin-2 receptor antagonists, such as tolvaptan, appear to slow down the growth of renal cysts and the slope of GFR decline. The current management of ADPKD patients is mostly based on correcting the risk factors for progression, i.e. encouraging (over)-hydration, normalizing blood pressure, stimulating smoking cessation. [less ▲]

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See detailInsight into SUCNR1 (GPR91) structure and function
Gilissen, Julie ULg; Jouret, François ULg; Pirotte, Bernard ULg et al

in Pharmacology & Therapeutics (2016)

SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs ... [more ▼]

SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate. According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy. The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor,more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed. [less ▲]

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See detailConcordance between iohexol and iothalamate plasma clearance
DELANAYE, Pierre ULg; JOURET, François ULg; LE GOFF, Caroline ULg et al

in American Journal of Kidney Diseases (2016)

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See detailFluorodeoxyglucose F Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection.
Lovinfosse, P.; Weekers, L.; Bonvoisin, C. et al

in American Journal of Transplantation (2016)

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary ... [more ▼]

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F18 (18 F-FDG), thus 18 F-FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 18 F-FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 +/- 18 minutes after administration of 3.2 +/- 0.2 MBq/kg of 18 F-FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 +/- 0.2, 1.6 +/- 0.3, 2.9 +/- 0.8, and 2.2 +/- 1.2 for the normal, borderline, AR, and other groups, respectively. One-way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r2 = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, 18 F-FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs 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 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 detailImpact of timing administration of mesenchymal stromal cells on serum creatinine following renal ischemia/ reperfusion in rats
ERPICUM, Pauline ULg; Rowart, Pascal ULg; POMA, Laurence ULg 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 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 detailRenal ischemia/reperfusion decreases the expression of DPP-4
Rowart, Pascal ULg; ERPICUM, Pauline ULg; Defraigne, Jean-Olivier ULg et al

Conference (2015, April 24)

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See detailLe cas clinique du mois : prise en charge d'une hypophosphatémie
HUART, Justine ULg; DUBOIS, Bernard ULg; Krzesinski, Jean-Marie ULg et al

in Revue Médicale de Liège (2015), 70(4), 163-168

Hypophosphatemia is defined by a serum phosphate level lower than 0.8 mmol/l. If hypophosphatemia is chronically maintained, it is associated with muscular, osteous, neurological or cardio-respiratory ... [more ▼]

Hypophosphatemia is defined by a serum phosphate level lower than 0.8 mmol/l. If hypophosphatemia is chronically maintained, it is associated with muscular, osteous, neurological or cardio-respiratory disorders. We describe a patient with isolated hypophosphatemia, detail the mechanisms of phosphate homeostasis, and envisage the differential diagnosis of hypophosphatemia. Furthermore, we propose a sequential decisional algorithm based on basic biological tests and few complementary investigations. Treatment options are reviewed. [less ▲]

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See detailEpidémiologie de la lithiase urinaire sur base d'une analyse morpho-constitutionnelle
Castiglione, Vincent ULg; JOURET, François ULg; Bruyère, Olivier ULg et al

in Néphrologie & Thérapeutique (2015), 11

Urolithiasis is a common condition, with a prevalence of 10% and a male/female ratio above 1 according to large national series. Various types of urinary stones have been described upon their mineral ... [more ▼]

Urolithiasis is a common condition, with a prevalence of 10% and a male/female ratio above 1 according to large national series. Various types of urinary stones have been described upon their mineral content and/or their morphology. Hence, a combined morpho-constitutional (M-C) classification has been proposed. In order to detail the prevalence of urolithiasis in general and of each M-C type in particular upon age and gender in Belgium, we retrospectively studied the database of a reference center for urolithiasis analysis. Between 2010 and 2013, 2195 stones were characterized. We excluded 45 nonbiological stones and 281 stones, which originated from outside the study zone. Among 1869 stones,1293 (69.2%) affected men. Prevalence peak of urolithiasis was observed between 50–60 years of age in both genders. The M-C analysis was available for 1854 stones (99.2%): multiple morphological types were concomitantly identified in 49.3%. In the whole population, the main mineral constituent was whewellite (54.4%), mainly organized as type Ia (94%). Weddellite was found in 19.8%, with an equal distribution between types IIa and IIb. Uric acid was the 3rd most frequent constituent in man, with a similar distribution between IIIa and IIIb. Phosphate was uncommon in man (8.2%), but frequent in woman (26.6%) with a type IVa1 organization. Prevalence of M-C types changes with aging, i.e. decrease of weddellite and increase of whewellite and uric acid in both genders. This retrospective analysis of a single-center database of urinary stones helps characterize the M-C epidemiology of urolithiasis in Belgium. [less ▲]

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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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