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 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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See detailIn-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction.
Dachy, Angelique; Paquot, Francois; Debray, François-Guillaume ULg et al

in Pediatric nephrology (Berlin, Germany) (2015), 30(6), 1027-31

BACKGROUND: The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin ... [more ▼]

BACKGROUND: The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai-Barrow/facio-oculo-acoustico-renal syndrome (DB/FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear. CLINICAL CASE: A 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene. CONCLUSIONS: The functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin. [less ▲]

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See detailDeficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.
Onclinx, Cecile; Dogne, Sophie; Jadin, Laurence et al

in Haematologica (2015)

Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are the hyaluronidases 1 and 2, none of which is active in the bloodstream. We generated ... [more ▼]

Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are the hyaluronidases 1 and 2, none of which is active in the bloodstream. We generated hyaluronidase 2 deficient mice. They suffer from mild chronic anemia and thrombocytopenia, in parallel with a 10-fold increase in plasma hyaluronan concentration. The current study explores the mechanism of these hematological anomalies. The decreased erythrocyte and platelet counts were assigned to peripheral consumption. The erythrocyte half-life was reduced from 25 to 8 days without signs of premature aging. Hyaluronidase 2 deficient platelets were functional. Major intrinsic defects in erythrocyte membrane or stability, as well as detrimental effects of high hyaluronan levels on erythrocytes, were ruled out in vitro. Normal erythrocytes transfused into hyaluronidase 2 deficient mice were quickly destroyed but neither splenectomy nor anti-C5 administration prevented from chronic hemolysis. Schistocytes were present in hyaluronidase 2 deficient smears at a level of 1 to 6%, while virtually absent in control mice. Hyaluronidase 2 deficient mice had increased markers of endothelial damage and microvascular fibrin deposition, without renal failure, accumulation of ultra-large multimers of von Willebrand factor, deficiency of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13), or hypertension. There was no sign of structural damage in hepatic or splenic sinusoids, or in any other microvessels. We conclude that hyaluronidase 2 deficiency induces chronic thrombotic microangiopathy with hemolytic anemia in mice. The link between this uncommon condition and hyaluronidase 2 remains to be explored in man. [less ▲]

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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 (2015)

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 detailMesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.
Rowart, Pascal ULg; Erpicum, Pauline; Detry, Olivier et al

in Journal of immunology research (2015), 2015

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and ... [more ▼]

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT. [less ▲]

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