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See detailMesenchymal Stromal Cells in Solid Organ Transplantation.
VANDERMEULEN, Morgan ULiege; ERPICUM, Pauline ULiege; WEEKERS, Laurent ULiege et al

in Transplantation (2020), 104(5), 923-936

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These ... [more ▼]

Over the past decade, the clinical application of mesenchymal stromal cells (MSCs) has generated growing enthusiasm as an innovative cell-based approach in solid organ transplantation (SOT). These expectations arise from a significant number of both transplant- and non-transplant-related experimental studies investigating the complex anti-inflammatory, immunomodulatory and tissue-repair properties of MSCs. Promising preclinical results have prompted clinical trials using MSC-based therapy in SOT. In the present review, the general properties of MSCs are summarized, with a particular emphasis on MSC-mediated impact on the immune system and in the ischemic conditioning strategy. Next, we chronologically detail all clinical trials using MSCs in the field of SOT. Finally, we envision the challenges and perspectives of MSC-based cell therapy in SOT. [less ▲]

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See detailObserver variability in the assessment of renal (18)F-FDG uptake in kidney transplant recipients.
JADOUL, Alexandre ULiege; LOVINFOSSE, Pierre ULiege; BOUQUEGNEAU, Antoine ULiege et al

in Scientific Reports (2020), 10(1), 4617

(18)F-FDG PET/CT imaging may help non-invasively disprove the diagnosis of acute kidney allograft rejection (AR) in kidney transplant recipients (KTR). The present study aims at evaluating the ... [more ▼]

(18)F-FDG PET/CT imaging may help non-invasively disprove the diagnosis of acute kidney allograft rejection (AR) in kidney transplant recipients (KTR). The present study aims at evaluating the repeatability and reproducibility of the quantification of renal (18)F-FDG uptake in KTR. We prospectively performed (18)F-FDG PET/CT in 95 adult KTR who underwent surveillance transplant biopsy between 3 to 6 months post transplantation. Images were obtained 180 minutes after injecting 3 MBq (18)F-FDG per kg body weight. Mean standard uptake value (SUVmean) of kidney cortex was independently measured by 2 experienced observers in 4 volumes of interest (VOI) distributed in the upper (n = 2) and lower (n = 2) poles. The first observer repeated SUV assessment in the uppermost VOI, blinded to the initial results. Intra-class correlation coefficients (ICC) and Bland-Altman plots were calculated. An ICC of 0.96 with 95%CI of [0.94; 0.97] was calculated for the intra-observer measurements. The ICC for inter-observer reproducibility for each VOI was 0.87 [0.81-0.91], 0.87 [0.81-0.91], 0.85 [0.78-0.89] and 0.83 [0.76-0.88] for the upper to the lower renal poles, respectively. The repeatability and reproducibility of the quantification of kidney allograft (18)F-FDG uptake are both consistent, which makes it transferrable to the clinical routine. [less ▲]

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See detailActualités thérapeutiques dans les erreurs innées du métabolisme
Debray, François-Guillaume ULiege; WEEKERS, Laurent ULiege; Dadoumont, C. et al

in Revue Médicale de Liège (2020), 75(5-6), 420-425

Inborn errors of metabolism (IEM) represent a vast group of orphan genetic disorders associated with enzyme deficiencies, substrates accumulation and products depletion. For several decades, the ... [more ▼]

Inborn errors of metabolism (IEM) represent a vast group of orphan genetic disorders associated with enzyme deficiencies, substrates accumulation and products depletion. For several decades, the cornerstone of life-saving therapies in IEM was based on extreme manipulations of the nutritional intakes. Such outstanding dietary engineering is still relevant today, but new therapeutic avenues have emerged last years, based on better pathophysiological understanding and technological advances. In this paper, we summarize current and new therapeutic options in the field of IEM. [less ▲]

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See detail5-Year outcomes of the prospective and randomized cistcert study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients.
Pipeleers, Lissa; Abramowicz, Daniel; Broeders, Nilufer et al

in Transplant international : official journal of the European Society for Organ Transplantation (2020)

BACKGROUND: Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The Cistcert study ... [more ▼]

BACKGROUND: Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The Cistcert study compared the efficacy and safety of these two strategies. METHODS: In this multi-center, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA) and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). RESULTS: Five-year patient (89% vs 86%; p=NS) and death-censored graft survival (95% vs 96%; p=NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm respectively. (51) CrEDTA clearance was comparable in the intention-to-treat analysis, but in the on-treatment population, the EVL/MPA/steroids arm exhibited a superior (51) CrEDTA clearance at 1 and 5 years after transplantation (61.6 vs 52.4, p=0.05 and 59.1 vs 46.2mL/min/1.73 m(2) , p=0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of post-transplant diabetes (26% versus 6%, p=0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. CONCLUSIONS: Both regimens provide an excellent long-term patient and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection. [less ▲]

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See detailRepeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis
Assfalg, V.; Selig, K.; Tolksdorf, J. et al

in Transplant International (2020), 33(6), 617-631

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15 ... [more ▼]

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT. © 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT [less ▲]

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See detailApports diagnostiques et pronostiques de la biopsie et du PET-CT au 18F-FDG du greffon rénal réalisés au cours de la première année post-transplantation.
WEEKERS, Laurent ULiege

Doctoral thesis (2019)

Kidney transplant long-term outcome relies on numerous factors out of which several occur during the first year after transplantation. It is also during this phase that most of the treatment options are ... [more ▼]

Kidney transplant long-term outcome relies on numerous factors out of which several occur during the first year after transplantation. It is also during this phase that most of the treatment options are decided. With progresses of immunosuppression, a lot of the immune related injuries have become clinically silent which, nowadays, still implies that a surveillance biopsy (SB) is performed for the diagnosis of subclinical rejection (SCAR). Moreover those improvements in controlling the alloimmune response together with less stringent criteria for acceptance of both recipients and donors have led to a growing complexity of performing the diagnosis for acute transplant kidney dysfunction. Here also, obtaining a transplant biopsy remains the gold standard for evaluating the causes of acute renal dysfunction, but the diagnostic yield of this procedure has decreased due to a raising proportion of those for-cause biopsies (fcB) revealing no signs of rejection (defining what is called acute dysfunction with non rejection or ADNR). This work concentrates on the lessons learned from both the SB and the fcB during the first year post kidney transplantation under modern immunosuppression. In the first part of this analysis, we have evaluated the incidence, causes and consequences of ADNR. We have shown that this polymorphic entity is quite frequent in our practice with an incidence rate of 72%. As a group, ADNR is associated with lower estimated glomerular filtration rate (eGFR) at one year post-transplantation. Moreover a higher proportion of patients with ADNR present with fast declining eGFR from 12 to 24 months post transplantation (a surrogate marker for future graft loss). The second part of this thesis is a critical evaluation of our clinical protocol of SB driven-steroid withdrawal concentrating on safety, efficiency and usefulness of the process. The serious adverse event-rate post-SB was 2.8%, out of which 0.4% necessitating invasive procedures. Out of an initial cohort of 502 kidney transplants, 481 were analyzed. SB revealed signs of SCAR (including borderline changes) in 27% of cases. Per-protocol SW was achieved in 35% of patients, an extra 10% of SW were performed either without SB (8%) or despite a SCAR (2%). Late biopsy proven acute rejection (BPAR) rates were respectively of 6%, 8% and 22% in these 3 groups. We have also identified sub-clinical antibody-mediated rejection as an independent risk factor for late BPAR in this cohort. The SB-driven SW strategy was associated with both total and death-censored long-term outcome; the per-protocol SW group showing one of the best kidney transplants longevity. There is a need non-invasive markers of acute rejection because kidney biopsy is an invasive procedure with relatively low yield both in the settings of acute dysfunction or as part of a systematic surveillance strategy. The last part of this work was dedicated to the validation of 18F-FDG PET-CT as a non-invasive marker of acute rejection. In a first pilot study on 32 patients, it was compared to the results of a concomitant fcB. The standardized mean uptake value (SUV) was shown to correlate with the inflammation within the kidney as scored by the Banff classification. Moreover, a mean SUV above a threshold of 1.6 had a negative predictive value (NPV) of 100% for BPAR, thereby providing an attractive tool to rule out the necessity of performing a biopsy when faced with acute renal dysfunction. In a second analysis, the ability of 18F-FDG PET-CT to pick-out SCAR was tested in a cohort of 92 SB with similar encouraging results, the NPV reaching 98% in this case. In conclusion, we have shown that individualized adaptation of immunosuppression taking into account the degree of alloimmune response is feasible and safe. However, it necessitates an invasive procedure that could frequently be avoided provided we could rely on non-invasive markers of rejection. Based on our work, 18F-FDG PET-CT stands out as a potential candidate for such an “iconomarker” to guide decision-making prior to biopsy. As a future perspective of this work, we propose to confirm these findings in a prospective randomized controlled trial comparing our current protocol of SB-driven SW with an iconomarker-based strategy of SW. [less ▲]

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See detail"Acute kidney dysfunction with no rejection" is associated with poor renal outcomes at 2 years post kidney transplantation.
PAQUOT, Francois ULiege; WEEKERS, Laurent ULiege; BONVOISIN, Catherine ULiege et al

in BMC Nephrology (2019), 20(1), 249

BACKGROUND: "Acute kidney dysfunction with no rejection" (ADNR) corresponds to acute kidney injury without histological evidence of acute rejection (AR) in kidney transplant recipients (KTR). The ... [more ▼]

BACKGROUND: "Acute kidney dysfunction with no rejection" (ADNR) corresponds to acute kidney injury without histological evidence of acute rejection (AR) in kidney transplant recipients (KTR). The prognosis of ADNR is unknown. METHODS: From 2007 to 2015, we categorized KTR with for-cause kidney biopsy within the first 12 months post kidney transplantation (KTx) into ADNR (n = 93) and biopsy-proven AR (n = 22). Controls (C, n = 135) included KTR with no ADNR or AR within the first 24 months post-KTx. A piecewise linear regression with a single fixed-knot at 12 months served to establish intercepts and slopes of MDRD-eGFR variations from 12 to 24 months. The percentage of KTR with >/=30% reduction of eGFR from 12 to 24 months was calculated as a surrogate marker of future graft loss. RESULTS: The median time for for-cause biopsy was 22 [10-70] and 13 [7-43] days for ADNR and AR, respectively. At 12 months, eGFR was significantly higher in C (57.6 +/- 14.9 mL/min/1.73m(2)) vs. ADNR (43.5 +/- 15.4 mL/min/1.73m(2), p < 0.0001) and vs. AR (46.5 +/- 15.2 mL/min/1.73m(2), p < 0.0065). The proportion of KTR with >/=30% reduction in eGFR from 12 to 24 months reached 16.3% in C vs. 29.9% in ADNR (p = 0.02) and vs. 15% in AR (not significant). CONCLUSIONS: ADNR is associated with poor outcomes within 2 years post-KTx. [less ▲]

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See detailInfusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study.
ERPICUM, Pauline ULiege; WEEKERS, Laurent ULiege; DETRY, Olivier ULiege et al

in Kidney International (2019), 95

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year ... [more ▼]

Mesenchymal stromal cells (MSCs) exhibit anti-inflammatory and immune-regulatory properties, and preclinical studies suggest a potential benefit in solid organ transplantation. We report on the 1-year follow-up of an open-label phase I-II trial of a single infusion of third-party MSC post-kidney transplantation, in addition to standard immunosuppression. Ten kidney transplant recipients from deceased donors received third-party bone marrow MSCs ( approximately 2 x 10(6)/kg) on day 3 +/- 2 post-transplant and were compared to 10 concurrent controls. No adverse effects were noted at MSC injection. One participant with a history of cardiac disease had a non-ST-elevation myocardial infarction approximately 3 hours after MSC infusion. Incidences of opportunistic infections and acute rejection were similar. At day 7 post-transplant, estimated glomerular filtration rate (eGFR) in MSC-treated recipients reached 48.6 ml/min/1.73m(2), compared to 32.5 ml/min/1.73m(2)in controls and 29.3 ml/min/1.73m(2)in our overall cohort of kidney transplant recipients. No difference in eGFR was found at 1 year. MSC-treated recipients showed increased frequencies of regulatory T cells at day 30, with no significant change in B cell frequencies compared to concurrent controls. Four MSC-treated participants developed antibodies against MSC or shared kidney-MSC HLA, with only 1 with MFI >1500. A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the intervention. MSC therapy is associated with increased regulatory T cell proportion and with improved early allograft function. Long-term effects, including potential immunization against MSC, remain to be studied. [less ▲]

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See detailLa tomographie par emission de positons au 18F-FDG en pathologie renale non oncologique : indications actuelles et perspectives.
HANSSEN, Oriane ULiege; LOVINFOSSE, Pierre ULiege; WEEKERS, Laurent ULiege et al

in Nephrologie & therapeutique (2019)

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological ... [more ▼]

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological nephrology since conventional radiological approaches after injection of contrast agents are relatively contra-indicated in patients with chronic kidney disease (CKD). PET/CT after i.v. injection of (18)F-fluoro-deoxy-glucose (FDG) is not toxic and is characterized by a high sensitivity. The level of irradiation ( approximately 5mSv) is acceptable. CKD does not significantly influence tissue uptake of (18)F-FDG. The purpose of the present review aims at detailing the non-oncological indications of (18)F-FDG PET/CT in general nephrology and after kidney transplantation. Particularly, (18)F-FDG PET/CT appears useful in the diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease, as well as in the characterization of retroperitoneal fibrosis. In kidney transplant recipients, (18)F-FDG PET/CT may help in the diagnostic work-up of suspected acute rejection, thereby eventually avoiding unnecessary kidney transplant biopsy. Perspectives in (18)F-FDG PET/CT imaging are discussed, including innovative approaches of image analysis. [less ▲]

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See detailOutcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study.
Menne, Jan; Delmas, Yahsou; Fakhouri, Fadi et al

in BMC Nephrology (2019), 20(1), 125

BACKGROUND: There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational ... [more ▼]

BACKGROUND: There are limited long-term outcome data in eculizumab-treated patients with atypical hemolytic uremic syndrome (aHUS). We report final results from the largest prospective, observational, multicenter study of patients with aHUS treated with eculizumab. METHODS: Patients with aHUS who participated in any of five parent eculizumab trials and received at least one eculizumab infusion were eligible for enrollment in a long-term follow-up study. Rates of thrombotic microangiopathy (TMA) manifestations off versus on eculizumab were evaluated. Additional endpoints included change from baseline estimated glomerular filtration rate (eGFR), long-term renal outcomes, and serious targeted treatment-emergent adverse events. RESULTS: Among 93 patients (0-80 years of age), 51 (55%) remained on eculizumab and 42 (45%) discontinued; for those who discontinued, 21 (50%) reinitiated therapy. Patients who reinitiated eculizumab had similar baseline clinical characteristics to patients who remained on eculizumab, with higher likelihood of genetic/autoimmune complement abnormalities, more prior TMAs, and longer disease course versus those who did not reinitiate. Mean eGFR improved rapidly and remained stable for up to 6 years on eculizumab. In patients who discontinued, there was a trend toward decreasing renal function over time from discontinuation. Additionally, off-treatment TMA manifestation rates were higher in those aged < 18 years at diagnosis, with identified genetic/autoimmune complement abnormalities, or history of multiple TMAs prior to eculizumab initiation. The safety profile was consistent with previous studies. Three definite and one possible meningococcal infections related to eculizumab were reported and resolved with treatment. Three deaths unrelated to eculizumab were reported. CONCLUSIONS: The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events. Pediatric age at disease onset and presence of genetic or autoimmune complement abnormalities are risk factors for TMA events off treatment. Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases. Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01522170 , January 31, 2012. [less ▲]

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See detailEculizumab prevents thrombotic microangiopathy in patients with atypical haemolytic uraemic syndrome in a long-term observational study.
Menne, Jan; Delmas, Yahsou; Fakhouri, Fadi et al

in Clinical Kidney Journal (2019), 12(2), 196-205

Background: Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). Methods: In five ... [more ▼]

Background: Eculizumab, a terminal complement inhibitor, is approved for atypical haemolytic uraemic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). Methods: In five parent studies, eculizumab effectively prevented TMA and improved renal and haematologic outcomes in patients with aHUS; therefore, these patients could enrol in this long-term, prospective, observational and multicentre study. The primary endpoint was the TMA manifestation rate off and on eculizumab post-parent study. Post hoc analyses evaluated rates during labelled versus non-labelled dosing regimens, and in those with versus without identified complement abnormalities. Serious targeted treatment-emergent adverse events (TEAEs) were evaluated. Results: Of 87 patients in the current study, 39 and 76 had off- and on-treatment periods, respectively; 17 (44%) with off periods reinitiated eculizumab. TMA manifestation rate per 100 patient-years was 19.9 off and 7.3 on treatment [hazard ratio (HR), 4.7; P = 0.0008]; rates were highest off treatment and lowest during labelled regimens. TMA manifestations with hospitalizations/serious AEs occurred more frequently off versus on treatment. TMA rates were higher among patients with identified complement abnormalities (HR, 4.5; P = 0.0082). Serious targeted TEAEs occurred at similar rates off and on treatment. Conclusions: As expected, patients with aHUS have increased risk of TMA manifestations after discontinuation of eculizumab or in the setting of non-labelled eculizumab dosing. Collectively, results show that maintaining eculizumab treatment minimizes risk of TMA, particularly in patients with identified complement abnormalities. Future studies are needed to further characterize TMA and longer term outcomes on labelled or non-labelled eculizumab regimens and after discontinuation of treatment. [less ▲]

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See detailControversies in the management of the haemodialysis-related arteriovenous fistula following kidney transplantation.
Vanderweckene, Pauline ULiege; Weekers, Laurent ULiege; Lancellotti, Patrizio ULiege et al

in Clinical Kidney Journal (2018), 11(3), 406-412

Arteriovenous fistula (AVF) is regarded as the best vascular access for chronic haemodialysis (HD). Still, AVF inherently causes significant haemodynamic changes. Although the necessity for vascular ... [more ▼]

Arteriovenous fistula (AVF) is regarded as the best vascular access for chronic haemodialysis (HD). Still, AVF inherently causes significant haemodynamic changes. Although the necessity for vascular access despite its putative cardiovascular complications favours AVF creation in patients under chronic HD, one may question whether sustaining a functional AVF after successful kidney transplantation extends the haemodynamic threat. Small prospective series suggest that AVF ligation causes rapid and sustained reduction in left ventricular hypertrophy. Still, the benefits of such a cardiac remodelling in long-terms of cardiovascular morbi-mortality still need to be proven. Furthermore, the elevation of diastolic blood pressure and arterial stiffness caused by AVF ligation may blunt the expected cardio-protection. Finally, the closure of a functioning AVF may accelerate the decline of kidney graft function. As a whole, the current management of a functioning AVF in kidney transplant recipients remains controversial and does not rely on strong evidence-based data. The individual risk of graft dysfunction and a return to chronic HD also needs to be balanced. Careful pre-operative functional assessments, including cardio-pulmonary testing and estimated glomerular filtration rate slope estimation, may help better selection of who might benefit the most from AVF closure. Large-scale prospective, ideally multi-centric, trials are essentially needed. [less ▲]

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See detailProspective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation.
Wissing, Karl M.; Abramowicz, Daniel; WEEKERS, Laurent ULiege et al

in American Journal of Transplantation (2018)

Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed ... [more ▼]

Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC-based regimen after stratification for type of glucose-lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12-month follow-up, resulting in significantly lower levels compared with the TAC group (6.0 +/- 0.9% vs 7.1 +/- 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006-001765-42). [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 ULiege; ERPICUM, Pauline ULiege; DETRY, Olivier ULiege et al

Conference (2017, March 16)

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3 ... [more ▼]

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3, third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recip- ients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. Seven comparable KTx recipients were included as controls. Informed consent was obtained. No 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. Ten months after KTx, 1 MSC patient had type B aortic dissection and STEMI. Four MSC patients had at least 1 opportunistic infection, whereas 3 controls had polyoma-BK viremia. At day 14, 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 46.5 ± 18.6 and 54.2 ± 16.3 ml/min, respectively (p, 0.42). Per-cause biopsies evidenced 1 bor- derline and 1 acute rejections in MSC group, whereas no AR was biopsy-proven in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches.MSC infusion was safe in all patients except one. Incidence of opportunist infections was similar in both groups. 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 detailNon-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients. Part I. In vivo imaging methods.
HANSSEN, Oriane ULiege; Erpicum, Pauline ULiege; LOVINFOSSE, Pierre ULiege et al

in Clinical Kidney Journal (2017), 10(1), 97-105

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, 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, 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, like 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 leukocytes may be detectable by 18F-fluoro-deoxy-glucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3epsilon, IP-10 and 18S RNA levels, have been identified. None of these approaches has been adopted yet in the clinical follow-up of KTRs, but standardization of procedures may help assess reproducibility and compare diagnostic yields in large prospective multicentric trials. [less ▲]

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See detailOutcomes of patients with atypical haemolytic uraemic syndrome with native and transplanted kidneys treated with eculizumab: a pooled post hoc analysis.
Legendre, Christophe M.; Campistol, Josep M.; Feldkamp, Thorsten et al

in Transplant International (2017)

Atypical haemolytic uraemic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four ... [more ▼]

Atypical haemolytic uraemic syndrome (aHUS) often leads to end-stage renal disease (ESRD) and kidney transplantation; graft loss rates are high due to disease recurrence. A post hoc analysis of four prospective clinical trials in aHUS was performed to evaluate eculizumab, a terminal complement inhibitor, in patients with native or transplanted kidneys. The trials included 26-week treatment and extension periods. Dialysis, transplant and graft loss were evaluated. Study endpoints included complete thrombotic microangiopathy (TMA) response, TMA event-free status, haematologic and renal parameters and adverse events. Of 100 patients, 74 had native kidneys and 26 in the transplant subgroup had a collective history of 38 grafts. No patients lost grafts and only one with pre-existing ESRD received a transplant on treatment. Efficacy endpoints were achieved similarly in both subgroups. After 26 weeks, mean absolute estimated glomerular filtration rate increased from baseline to 61 and 37 ml/min/1.73 m2 in native (n = 71; P < 0.0001) and transplanted kidney (n = 25; P = 0.0092) subgroups. Two patients (one/subgroup) developed meningococcal infections; both recovered, one continued therapy. Eculizumab was well tolerated. Eculizumab improved haematologic and renal outcomes in both subgroups. In patients with histories of multiple graft losses, eculizumab protected kidney function. [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 detailAge-dependent reference intervals for estimated and measured glomerular filtration rate
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