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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 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.Les erreurs innées du métabolisme (EIM) représentent un groupe de conditions génétiques associées à une déficience enzymatique causant une accumulation du substrat en amont de la réaction et une déficience du produit en aval. Pendant des décennies, la pierre angulaire du traitement de ces affections a été basée sur des régimes drastiquement restrictifs. Ces manipulations diététiques extrêmes sont encore aujourd’hui d’actualité, mais l’arsenal thérapeutique s’est considérablement élargi ces dernières années, basé sur de meilleures connaissances physiopathologiques et sur des progrès technologiques et pharmacologiques. Dans cet article, nous résumons les différentes stratégies et nouveautés thérapeutiques dans le domaine des erreurs innées du métabolisme. [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 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 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
Pottel, Hans; DELANAYE, Pierre ULiege; WEEKERS, Laurent ULiege et al

in Clinical Kidney Journal (2017), 10(4), 545-551

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

in Nephrology Dialysis Transplantation (2017)

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

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

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

in Clinical Kidney Journal (2017)

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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