Nilufer Broeders
Université libre de Bruxelles
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Featured researches published by Nilufer Broeders.
The New England Journal of Medicine | 2012
Sylvie Euvrard; Emmanuel Morelon; Lionel Rostaing; Eric Goffin; Anabelle Brocard; I. Tromme; Nilufer Broeders; Véronique Del Marmol; Valérie Chatelet; Anne Dompmartin; Michèle Kessler; Andreas L. Serra; Günther F.L. Hofbauer; Claire Pouteil-Noble; Josep M. Campistol; Jean Kanitakis; Adeline Roux; Evelyne Decullier; Jacques Dantal
BACKGROUND Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. METHODS In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus. RESULTS Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups. CONCLUSIONS Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
Transplantation | 2000
Karl Martin Wissing; Daniel Abramowicz; Nilufer Broeders; Pierre Vereerstraeten
BACKGROUND Whereas acute rejection is the main risk factor for the occurrence of chronic rejection, mechanisms in addition to the donor-specific immune response probably contribute to late allograft failure. In this study, we investigated the possible role of hypercholesterolemia in the incidence of chronic kidney graft loss. METHODS By using the actuarial method, we retrospectively analyzed the long-term loss of cadaveric kidney grafts in patients who had a functioning graft at 1 year and had received a transplant and undergone cyclosporin A therapy in our center between 1983 and 1997. RESULTS As observed previously, patients with acute rejection during the 1st posttransplant year (n=198) had significantly higher actuarial graft loss at 10 years compared with those free of acute rejection (n=244). In patients free of acute rejection at 1 year, hypercholesterolemia (> or =250 mg/dl) had no impact on graft loss at 10 years. On the contrary, in patients with previous acute rejection, those with hypercholesterolemia (n=59) had a higher immunological (36.0% vs. 19.2%; P<0.01) and overall (50.0% vs. 25.3%; P<0.01) graft loss at 10 years compared with patients with serum cholesterol <250 mg/dl (n=139). Among patients with 1st year acute rejection, hypercholesterolemia was associated with a significant increase in graft loss in male but not in female recipients. Multivariate analysis confirmed that hypercholesterolemia was an independent risk factor for chronic graft loss in male patients (P<0.05). CONCLUSION Hypercholesterolemia is an independent risk factor for kidney graft loss from chronic rejection in male patients with previous acute rejection. Correction of hypercholesterolemia could help to reduce kidney graft loss caused by chronic rejection in this category of patients.
Transplantation | 2008
Dimitri Mikhalski; Karl Martin Wissing; Lidia Ghisdal; Nilufer Broeders; Marie Touly; Anh Dung Hoang; Patricia Loi; Freddy Mboti; Vincent Donckier; Pierre Vereerstraeten; Daniel Abramowicz
Background. The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival. Methods. We retrospectively reviewed the charts of 611 renal transplantations between 1996 and 2005. Most patients received a calcineurin inhibitor as maintenance therapy, either cyclosporine (43%) or tacrolimus (52%) and 76% of the patients received an antilymphocyte induction therapy. Study endpoints were DGF, first-year AR, and long-term graft survival. Uni- and multivariate analyses were performed to determine factors that may have influenced the study outcomes. Results. DGF was observed in 16.2% of patients. Both older donor age and longer CIT were significant risk factors for DGF. DGF rates were similar whether patients received a calcineurin inhibitor before transplantation or not. AR occurred in 16.5% of grafts during the first year. Independent predictors of AR by multivariate analysis were duration of dialysis, CIT, current panel-reactive lymphocytotoxic antibody more than 5%, and the number of human leukocyte antigen-A, B, and DR mismatches. Each hour of cold ischemia increases the risk of rejection by 4%. With respect to death-censored graft survival, three pretransplant parameters emerged as independent predictors of graft loss: younger recipient age, peak panel-reactive lymphocytotoxic antibody more than 5% and longer CIT. The detrimental effect of CIT on graft survival was entirely because of its propensity to trigger AR. When AR was added to the multivariate Cox model, CIT was no longer significant whereas first-year AR became the most important predictor of graft loss (Hazards ratio, 4.6). Conclusion. Shortening CIT will help to decrease not only DGF rates but also AR incidence and hence graft loss. Patients with prolonged CIT should receive adequate immunosuppression, possibly with antilymphocyte preparations, to prevent AR occurrence.
Transplantation | 2005
K. Martin Wissing; Nilufer Broeders; Rodrigo Moreno-Reyes; Christine Gervy; Daniel Abramowicz
Background. New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation. The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting. Methods. Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone were randomized to receive either 400 mg daily oral calcium (Ca group, n=44) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 (CaVitD group, n=46). Bone mineral density (BMD) was measured by dual energy absorptiometry at baseline and at 1 year. Results. The overall population experienced a moderate but significant −2.3±0.9% loss of lumbar spine BMD (P<0.01) but no bone loss at the femoral neck and shaft during the first posttransplant year. Bone loss tended to be slightly higher in the CaVitD group, but the difference did not reach statistical significance. Patients in the CaVitD group had significantly higher 25(OH) but not 1,25(OH)2 vitamin D levels. We observed a highly significant negative correlation between 25(OH) vitamin D and intact parathyroid hormone (iPTH) serum levels. Conclusions. Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year. Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation.
Transplant International | 2007
Lidia Ghisdal; Nora Ben Bouchta; Nilufer Broeders; Laurent Crenier; Anh Dung Hoang; Daniel Abramowicz; Karl Martin Wissing
Tacrolimus (TRL) increases the incidence of new‐onset diabetes mellitus after transplantation (NODAT). Little is known about whether conversion from TRL to cyclosporine A (CsA) improves glucose metabolism in patients with NODAT. We retrospectively analysed glucose metabolism parameters in 54 TRL‐treated renal transplant patients who developed NODAT. Thirty‐four were converted to CsA whereas 20 patients continued TRL. After conversion, fasting plasma glucose decreased from 146 ± 64 to 104 ± 20 mg/dl (P < 0.0001) and HbA1c levels decreased from 6.8 ± 0.8% to 6.0 ± 0.6% (P < 0.0001) after 1 year of follow‐up. The remission rate of NODAT reached 42% (95% confidence interval 24–59%) 1 year after conversion versus 0% in the control group (P = 0.001). Blood pressure and lipid levels were stable after conversion although the use of statins significantly increased (P < 0.01). The conversion was safe in terms of graft function and acute rejection episodes. The 1‐year patient survival and graft survival rate were 100%. In conclusion, our results suggest a significant improvement of glucose metabolism after conversion to CsA in renal transplant patients with NODAT.
Transplantation | 2011
Jean-Michel Hougardy; Nilufer Broeders; Mireille Kianda; Annick Massart; Phillippe Madhoun; Alain Le Moine; Anh Dung Hoang; Dimitri Mikhalski; Karl Martin Wissing; Daniel Abramowicz
Background. Advagraf is a slow release form of tacrolimus with once-daily formulation. The potential advantages of Advagraf are better adherence and a safer profile by avoiding toxic peak concentrations. In this study, we evaluated the required daily doses of tacrolimus and subsequent blood levels on conversion from Prograf to Advagraf among kidney transplant recipients. Methods. We retrospectively reviewed data from 55 patients for whom a switch from Prograf to Advagraf was identified. Tacrolimus daily doses and concomitant blood levels were analyzed at several time points ranging from 3 months before to 6 months after conversion. Results. We observed a significant increase in tacrolimus daily doses, starting with a dose of 0.063 mg/kg of Prograf, increasing up to 0.081 mg/kg of Advagraf at 6 months (P<0.0001). After conversion, we observed a quick and sustained decrease in trough tacrolimus levels, decreasing from 8.05 ng/mL at day 0 to 6.30 ng/mL at day 180 (P=0.0009). At 6 months, 35% of patients experienced a decrease in trough levels of more than 30%. Creatinine values remained stable over time, and no patient experienced an acute rejection episode. Conclusions. Contrary to the manufacturer instructions, we found a significant decrease in tacrolimus exposure after switching to Advagraf. Therefore, the switch from Prograf to Advagraf should be performed under close medical supervision.
Transplantation | 2008
Karl Martin Wissing; Guy Fomegné; Nilufer Broeders; Lidia Ghisdal; Anh Dung Hoang; Dimitri Mikhalski; Vincent Donckier; Pierre Vereerstraeten; Daniel Abramowicz
Background. New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. Methods. We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. Results. Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. Conclusions. Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.
Clinical Journal of The American Society of Nephrology | 2011
Nilufer Broeders; Anneleen Hombrouck; Anne Lemy; Karl Martin Wissing; Judith Racapé; Karine Gastaldello; Annick Massart; Steven Van Gucht; Laura Weichselbaum; Aurélie De Mul; Bernard Brochier; Isabelle Thomas; Daniel Abramowicz
BACKGROUND AND OBJECTIVES In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: ≥4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. RESULTS The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39). CONCLUSIONS The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.
Transplantation | 2006
Karl Martin Wissing; Philippe Unger; Lydia Ghisdal; Nilufer Broeders; Guy Berkenboom; Yvon Carpentier; Daniel Abramowicz
Background. Hypercholesterolemia is a frequent complication in renal transplant patients treated with cyclosporine A (CsA). Whether it is preferable to treat hypercholesterolemia with statins or to switch patients from CsA to tacrolimus (TRL) has not been investigated. Methods. Twelve CsA-treated kidney transplant recipients with hypercholesterolemia were successively crossed over from CsA alone to: CsA plus atorvastatin; TRL alone; and TRL plus atorvastatin. Total cholesterol (C), Low density lipoprotein (LDL)-C, high density lipoprotein (HDL)-C, LDL and HDL alpha-tocopherol content, lag-time of LDL oxidation, plasma levels of oxidized LDL and the percentage of small dense LDL were assayed at the end of each treatment period. Endothelial function was assessed by high resolution ultrasound measurement of flow-mediated brachial artery vasodilatation (FMD). Results. Atorvastatin therapy was more efficient in reducing total cholesterol and LDL-C levels than conversion from CsA to TRL. Combining TRL with atorvastatin further reduced LDL-C levels as compared to TRL alone, but was no more efficient than the CsA-statin combination. Neither atorvastatin therapy nor conversion to TRL significantly changed the proportion of dense LDL, lipoprotein alpha-tocopherol contents or the lag time of LDL oxidation. Addition of atorvastatin to CsA increased FMD from 4.0±1.8% to 6.5±4.0% (P<0.05 vs. CsA). Conversion from CsA to TRL caused a slight improvement in FMD (5.1±2.1%, P<0.05 vs. CsA). Adding atorvastatin to TRL had no detectable effect on FMD (5.5±2.3%, P=NS vs. TRL). Conclusions. Atorvastatin was more efficient in reducing total and LDL cholesterol levels of CsA-treated renal transplant patients than conversion to TRL and significantly improved endothelial dysfunction.
Nephrology Dialysis Transplantation | 2011
Lidia Ghisdal; Nilufer Broeders; Karl Martin Wissing; Joseph Mbaba Mena; Anne Lemy; Walter Wijns; Olivier Pradier; Vincent Donckier; Judith Racapé; Pierre Vereerstraeten; Daniel Abramowicz
BACKGROUND The aim of our study was to evaluate the prevalence of acquired thrombophilic factors in Stage V chronic kidney disease (CKD) patients according to dialysis modality, the rate of correction of these factors 1 month after renal transplantation and their impact on cardiovascular or thromboembolic events at 1 year. METHODS Three hundred and ten patients were prospectively screened for seven thrombophilic factors at transplantation; 215 of them were also assayed 1 month after. All the patients received prophylactic acetylsalicylic acid, started before transplantation. RESULTS The prevalence of thrombophilic factors was significantly higher in patients under dialysis (n = 289) than in patients not yet on dialysis (n = 21) (74 versus 52.4%; P = 0.03) but was similar in haemodialysis and peritoneal dialysis patients (74.2 versus 73.2%). One month after transplantation, the global prevalence of thrombophilic factors had dropped from 74.4 to 44.7% (P < 0.001). Most thrombophilic factors had disappeared after transplantation: antithrombin deficiency: 13.5 versus 0.9%; P < 0.001, protein C deficiency: 12.1 versus 1.9%; P < 0.001, protein S deficiency: 3.7 versus 1.4%; P = 0.1, lupus anticoagulant: 37.7 versus 8.4%; P < 0.001 and antiphospholipid antibodies: 29.3 versus 12.6%; P < 0.001. The prevalence of activated protein C resistance, which reflects inherited factor V (FV) Leiden, was unchanged (1.9%), while the prevalence of elevated factor VIIIc increased from 20.9 to 30.7%, P < 0.001. The incidence of cardiovascular or thromboembolic events 1 year after transplantation was similar in patients with more than or equal to one thrombophilic factor at 1 month (5.2%) versus thrombophilic-free patients (6.7%). CONCLUSION Acquired thrombophilic factors are highly prevalent among Stage V CKD patients. Most thrombophilic factors are corrected 1 month after transplantation.