References of "ERPICUM, Pauline"
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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 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 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 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 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 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 detailMesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion.
Erpicum, Pauline ULg; DETRY, Olivier ULg; WEEKERS, Laurent ULg et al

in Nephrology Dialysis Transplantation (2014), 29

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of ... [more ▼]

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning. [less ▲]

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See detailTwo novel mutations of the CLDN16 gene cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
Hanssen, Oriane ULg; CASTERMANS, Emilie ULg; BOVY, Christophe ULg et al

in Clinical Kidney Journal (2014), 7

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins ... [more ▼]

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis is an autosomal-recessive disease caused by mutations in the CLDN16 or CLDN19 genes, which encode tight junction-associated proteins, claudin-16 and -19. The resultant tubulopathy leads to urinary loss of Mg2+ and Ca2+, with subsequent nephrocalcinosis and end-stage renal disease (ESRD). An 18-year-old boy presented with chronic kidney disease and proteinuria, as well as hypomagnesaemia, hypercalciuria and nephrocalcinosis. A kidney biopsy revealed tubular atrophy, interstitial fibrosis and segmental sclerosis of some glomeruli. Two novel mutations in the CLDN16 gene were identified: c.340C>T (nonsense) and c.427+5G>A (splice site). The patient reached ESRD at 23 and benefited from kidney transplantation. [less ▲]

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See detailIntérêt de la chronothérapie dans le traitement de l'hypertension artérielle
VANDERWECKENE, Pauline ULg; ERPICUM, Pauline ULg; Krzesinski, Jean-Marie ULg

in Revue Médicale Suisse (2012), 8(351), 1604-1610

The interest of chronotherapy in the field of arterial hypertension is progressively rising, especially in treated hypertensive patients characterized by a small decrease of their blood pressure during ... [more ▼]

The interest of chronotherapy in the field of arterial hypertension is progressively rising, especially in treated hypertensive patients characterized by a small decrease of their blood pressure during the night, and therefore often presenting a high cardiovascular risk. There are more and more data showing that administration of one antihypertensive drug in the evening (and even aspirin) can improve the blood pressure control during the night and the day/night blood pressure pattern, and so can diminish the level of risk. The role of chronotherapy also emphasizes the interest of 24 h ambulatory blood pressure monitoring in the management of high risk hypertensive patients. [less ▲]

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