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Lionel Couzi,
Bruno Moulin,
Marie-Pascale Morin,
Laetitia Albano,
Michel Godin,
Benoit Barrou,
Eric Alamartine,
Emmanuel Morelon,
Sandrine Girardot-Seguin,
Laurence Mendes,
David Misdrahi,
Elisabeth Cassuto, Pierre Merville
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ABSTRACT: BACKGROUND: There have been few prospective studies on the natural history of nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective of this study was to prospectively evaluate the rate of and risk factors for NA in a French cohort of KTRs. METHOD: A total of 312 KTRs from eight French transplantation centers were included in this prospective, noninterventional cohort study. A computer-learning software package (the Organ Transplant Information System) was made available to all patients. RESULTS: Using the four-item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively. Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple treatment regimens including a small number of doses per day and a small number of tablets per day were associated with NA at M3 and M12, respectively. Other factors predictive of NA included failure to use the Organ Transplant Information System software package at M6 and patient reports of adverse events at M12 and M24. Importantly, we observed that physicians underestimated the prevalence of adverse events when compared to patient self-reporting. CONCLUSION: Our observed rate of medication NA in France is consistent with rates reported in previous studies. We found variability in NA risk factors over time as well as an unexpected risk factor (simple treatment regimens). These findings will be useful in developing effective adherence-promoting interventions.
Transplantation 11/2012; · 4.00 Impact Factor
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Antoine Thierry,
Georges Mourad,
Matthias Büchler,
Nassim Kamar,
Florence Villemain,
Anne-Elisabeth Heng,
Yannick Le Meur,
Gabriel Choukroun,
Olivier Toupance,
Christophe Legendre,
Patrick Lepogamp,
Michele Kessler, Pierre Merville,
Bruno Moulin,
Stéphane Quéré,
Arara Terpereau,
Kamel Chaouche-Teyara,
Guy Touchard
[show abstract]
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ABSTRACT: Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance.
In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine.
The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73 m(2), controls 60 ± 22 mL/min/1.73 m(2), P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045).
A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.
Nephrology Dialysis Transplantation 05/2012; 27(9):3651-9. · 3.40 Impact Factor
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Transplantation 04/2012; 93(8):e34-5. · 4.00 Impact Factor
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Laetitia Albano,
Eric Alamartine,
Olivier Toupance,
Bruno Moulin, Pierre Merville,
Jean Philippe Rerolle,
Rachel Tetaz,
Marie-Christine Moal,
Nassim Kamar,
Christophe Legendre,
Stéphane Quéré,
Fabienne Di Giambattista,
Arara Terpereau,
Jacques Dantal
[show abstract]
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ABSTRACT: Data in kidney transplant recipients regarding elimination of calcineurin inhibitor (CNI) therapy from a de novo regimen based on low CNI exposure and an mTOR inhibitor are sparse, and restricted to CNI elimination within the first six months post-transplant.
In a 12-month, randomized, multicenter, open-label study, kidney transplant patients who had received everolimus, low-exposure cyclosporine and corticosteroids from transplantation to month 12 (with proteinuria <1 g/24 h at month 12) were randomized to convert from cyclosporine to mycophenolate sodium 720 mg/day with increased everolimus exposure (6-10 ng/mL [CNI-free group], n=15) or continue unchanged (everolimus 3-8 ng/mL [CNI group], n=15).
Median (range) baseline mGFR was 54 (21-87) mL/min and 37 (range 18-69) mL/min (p=0.053) in the CNI-free and CNI groups, respectively, compared to 56 (18-126) mL/min and 32 (12-63) mL/min at month 12 (p=0.007). The between-group difference in change in mGFR from baseline to month 12 post-conversion (the primary endpoint) was -14.4 mL/min (95% CI -29.3 to 0.6 mL/min, p=0.059 [least squares mean]). Changes in serum creatinine and estimated GFR to month 12 were significantly in favor of CNI-free patients. One CNI patient experienced biopsy-proven acute rejection. Study drug was discontinued due to adverse events in one CNI-free patient (7%) and three CNI-treated patients (20.0%).
Elimination of CNI from a de novo regimen of everolimus with low-exposure CNI at one year post-transplant maintained efficacy and led to a non-significant but clinically relevant improvement in renal function, although patients numbers were low (n=30). Findings from this small study require confirmation in a larger controlled trial.
Annals of transplantation: quarterly of the Polish Transplantation Society 03/2012; 17(1):58-67. · 2.02 Impact Factor
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Gaëlle Lefrançois,
Cécile Chauvet,
Philippe Chauveau,
Maryvonne Hourmant,
Bruno Hurault de Ligny,
Christian Jacquelinet,
Anne Kolko, Pierre Merville,
Bruno Moulin,
Georges Mourad,
Lionel Rostaing,
Brigitte Zins,
Michèle Kessler,
Marie-Noëlle Peraldi
Néphrologie & Thérapeutique 02/2012; 8(2):72-3. · 0.47 Impact Factor
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Bruno Moulin, Pierre Merville,
Karine Renaudin,
David Buob,
Sophie Ferlicot,
Michel Delahousse,
Jacques Dantal,
Laetitia Albano,
Christelle Barbet,
Georges Mourad,
Laure-Hélène Noel
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ABSTRACT: The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ≥30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ≥30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73 m² with SB and 54 (15) mL/min/1.73 m² with NSB (P = 0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73 m² at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, P < 0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed.
Journal of Transplantation 01/2012; 2012:781263.
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ABSTRACT: Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16(+)γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients.
Blood 12/2011; 119(6):1418-27. · 9.90 Impact Factor
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Transplant International 05/2011; 24(5):e40-2. · 2.92 Impact Factor
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Lionel Couzi,
Caroline Araujo,
Gwendaline Guidicelli,
Thomas Bachelet,
Karine Moreau,
Delphine Morel,
Grégoire Robert,
Hervé Wallerand,
Jean-François Moreau,
Jean-Luc Taupin, Pierre Merville
[show abstract]
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ABSTRACT: Prognosis of renal transplants with positive flow cytometric crossmatch (FCXM) remains controversial.
We analyzed the outcome of these kidney transplant recipients by human leukocyte antigen (HLA) donor-specific antibodies (HLA-DSA) using single-antigen bead (SAB) assays in major histocompatibility complex classes I and II. We compared them with controls with a negative FCXM.
Forty-five patients consecutively transplanted with a positive FCXM had significantly more acute rejection episodes than the control patients (33.3% vs. 8.9%, P=0.002). Risk of acute rejection was increased with day 0 (D0) positive T-cell FCXM (odds ratio [OR]=9.04, P=0.002), D0 positive B-cell FCXM (OR=7.43, P=0.02), and D0 HLA-DSA identified by SAB assay (OR=6.5, P=0.03). The 21 patients with D0 positive FCXM and D0 HLA-DSA had more acute rejection (62%, P=0.0001) and a lower estimated glomerular filtration rate 1-year posttransplantation (P=0.0001), when compared with controls. Mainly anti-Cw and anti-DP HLA-DSA were found in patients displaying acute rejection. The remaining FCXM-positive patients displayed short-term outcomes similar to controls. The presence of HLA-DSA detected only by the SAB assay in the context of a negative FCXM crossmatch was not associated with increased risk of acute rejection.
Identification of HLA-DSA in D0 sera by the two sensitive techniques FCXM and SAB assay indicates which patients are at highest risk of subsequent acute allograft rejection and chronic allograft dysfunction.
Transplantation 03/2011; 91(5):527-35. · 4.00 Impact Factor
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Jacques Dantal,
François Berthoux,
Marie-Christine Moal,
Lionel Rostaing,
Christophe Legendre,
Robert Genin,
Olivier Toupance,
Bruno Moulin, Pierre Merville,
Jean-Philippe Rerolle,
François Bayle,
Pierre François Westeel,
Denis Glotz,
Niloufar Kossari,
Nicole Lefrançois,
Bernard Charpentier,
Stéphane Quéré,
Fabienne Di Giambattista,
Elisabeth Cassuto
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ABSTRACT: Immediate or early use of proliferation signal inhibitor (PSI)/mammalian target of rapamycin (mTOR) inhibitor therapy can avoid high exposure to calcineurin inhibitors but concerns exist relating to the risk of delayed graft function (DGF) and impaired wound healing with the mTOR sirolimus. CALLISTO was a 12-month, prospective, multicenter, open-label study. Deceased-donor kidney transplant patients at protocol-specified risk of DGF were randomized to start everolimus on day 1 (immediate everolimus, IE; n = 65) or week 5 (delayed everolimus, DE; n = 74). Incidence of the primary endpoint (biopsy-proven acute rejection, BPAR; graft loss, death, DGF, wound healing complications related to transplant surgery or loss to follow-up) was 64.6% and 66.2% in the IE and DE groups, respectively, at month 12 (P = 0.860). The overall incidence of BPAR was 20.1%. Median estimated glomerular filtration rate was 48 ml/min/1.73 m(2) and 49 ml/min/1.73 m(2) in the IE and DE groups, respectively, at month 12. DGF and wound healing complications were similar between groups. Adverse events led to study drug discontinuation in 17 IE patients (26.2%) and 28 DE patients (37.8%) (NS). In conclusion, introduction of everolimus immediately or early posttransplant in DGF-risk patients is associated with good efficacy, renal function and safety profile. There seems no benefit in delaying initiation of everolimus.
Transplant International 11/2010; 23(11):1084-93. · 2.92 Impact Factor
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Sébastien Hantz,
Françoise Garnier-Geoffroy,
Marie-Christine Mazeron,
Isabelle Garrigue, Pierre Merville,
Catherine Mengelle,
Lionel Rostaing,
Franck Saint Marcoux,
Marie Essig,
Jean-Philippe Rerolle,
Sébastien Cotin,
Raphaëlle Germi,
Sylvie Pillet,
Yvon Lebranchu,
Pascal Turlure,
Sophie Alain
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ABSTRACT: Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540).
Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected.
Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance.
These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.
Journal of Antimicrobial Chemotherapy 10/2010; 65(12):2628-40. · 5.07 Impact Factor
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ABSTRACT: Hemodialysis and kidney transplant are two treatments for renal failure, which lead to numerous changes in the patients' way of life. We have questioned ourselves on the different ways they could deal with those changes by studying the representations and the ritualisation that surrounds the sick. From 2005 to 2007, qualitative interviews, based on the method of life stories, were conducted with 35 patients with chronic renal failure in three Aquitaine's centres. The results show three main groups of representation both in pre-transplant and in post-transplant. Specific behaviours are tied to each group of representation that are beneficial or deleterious with respect to treatment or the patient's social life. We will show that, on the one hand, the patients who see the hemodialysis treatment as a traditional rite of passage cope with the situation more easily and on the other hand, we will stress that this representation is closely linked to how the patients will later accept the kidney transplant. So, we have been able to link the representations of hemodialysis patients and transplant experience. Then these results have a practical consequence for the caregivers who can use the tools of anthropology (the interview guide, analysis grid) through a program of therapeutic education, to precociously take care of patients who are likely to come up against issues after their kidney transplant.
Néphrologie & Thérapeutique 03/2010; 6(2):111-20. · 0.47 Impact Factor
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ABSTRACT: To determine and analyze the incidence, prognosis, and therapeutic strategy of de novo urological malignancies in a series of renal transplant recipients (RTRs).
A retrospective study of 1350 recipients between January 1998 and January 2008 was carried out; we reviewed the data of 42 de novo urological malignancies in 39 recipients.
There were 21 cases of prostate cancer, 13 cases of renal cell carcinoma in 10 patients, 3 cases of renal graft tumors, and 5 cases of transitional cell carcinoma of the bladder. The overall incidence of urological neoplasms was 3.1%. The mean age of cancer diagnosis was 60 +/- 8.3 years. The mean duration of dialysis before cancer diagnosis was 35 +/- 37.5 months. About 92% of patients underwent hemodialysis (34/39) and the remaining underwent peritoneal dialysis (5/39). All the 39 recipients received cadaveric kidneys. The mean follow-up period for this study was 33 +/- 34.4 months (range 2-160 months). There appears to be a greater risk of urological neoplasm in RTRs. Prostate cancer and renal carcinoma can be treated in a similar manner than in general population with encouraging oncological results and low morbidity. However, the transitional cell carcinoma of the bladder remains particularly aggressive requiring optimal treatment despite the morbidity concerning the intravesical therapy.
We can apply the standard medical and surgical treatment in RTRs, with encouraging oncological results if a strict screening program is established and followed by the patients.
Urology 10/2009; 75(1):126-32. · 2.43 Impact Factor
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Lionel Couzi,
Yann Levaillant,
Abdellah Jamai,
Vincent Pitard,
Regis Lassalle,
Karin Martin,
Isabelle Garrigue,
Omar Hawchar,
François Siberchicot,
Nicholas Moore,
Jean-François Moreau,
Julie Dechanet-Merville, Pierre Merville
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ABSTRACT: An increase in the number of blood gammadelta T cells follows cytomegalovirus (CMV) infection in kidney transplant recipients. These cells react against CMV-infected cells and tumor epithelial cells in vitro. We hypothesized that these CMV-induced gammadelta T cells play a protective role against cancer in kidney transplant recipients. We performed a longitudinal case-control study involving 18 recipients who developed cancer between 2 and 6 yr after transplantation and 45 recipients who did not. The median percentage of gammadelta T cells among total lymphocytes in patients with malignancies was significantly lower compared with that in control patients at 6, 12, and 18 mo before the diagnosis of cancer. Patients with a gammadelta T cell percentage of more than 4% were protected from cancer. An increase of the Vdelta2(neg) gammadelta T cell subset significantly associated with lower incidence of cancer only in recipients who experienced pre- or postgraft CMV infection. Finally, a retrospective follow-up of 131 recipients for 8 yr revealed that CMV-naive recipients had an approximately 5-fold higher risk of cancer compared with CMV-exposed patients. In summary, these results suggest a protective role of CMV exposure against cancer in kidney transplant recipients.
Journal of the American Society of Nephrology 09/2009; 21(1):181-8. · 9.66 Impact Factor
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ABSTRACT: Kidney transplant recipients infected with cytomegalovirus (CMV) undergo a persistent gammadelta T cell expansion in their peripheral blood. The anti-CMV function of these cells was previously demonstrated by their ability to kill CMV-infected cells in vitro.
To gain insight into the role of gammadelta T cells within the antiviral immune network, we compared the expansion kinetics of these T cells with that of CMV pp65-specific CD8(+) alphabeta T cells in the peripheral blood of twenty-one kidney transplant recipients.
Both the percentage and the absolute number of pp65-specific CD8(+) T cells and gammadelta T cells showed a concomitant increase and persistence in most of the kidney transplant recipients with CMV infection. Both cell subsets exhibited an effector/memory phenotype (CD28(-), CD27(-), and CD45RA(+)) that predominated for the entire follow-up period.
In conclusion, CMV-specific CD8(+) alphabeta T cells and gammadelta T cells share common expansion kinetics and a common effector phenotype, suggesting that these cell types act similarly in response to CMV infection.
The Journal of Infectious Diseases 09/2009; 200(9):1415-24. · 6.41 Impact Factor
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Laetitia Albano,
François Berthoux,
Marie-Christine Moal,
Lionel Rostaing,
Christophe Legendre,
Robert Genin,
Olivier Toupance,
Bruno Moulin, Pierre Merville,
Jean-Philippe Rerolle,
François Bayle,
Pierre François Westeel,
Denis Glotz,
Niloufar Kossari,
Nicole Lefrançois,
Bernard Charpentier,
Anne-Sandrine Blanc,
Fabienne Di Giambattista,
Jacques Dantal
[show abstract]
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ABSTRACT: Concerns about delayed graft function (DGF) and wound healing complications with sirolimus has led to suggestions that everolimus introduction could be delayed after transplantation.
In a prospective, multicenter, open-label study, deceased-donor kidney transplant recipients at protocol-specified risk of DGF (defined as > or =1 dialysis session during the first week posttransplant excluding day 1) were randomized to start everolimus therapy on day 1 posttransplant (immediate everolimus [IE]), or from week 5 (delayed everolimus [DE]) with mycophenolic acid until everolimus was initiated. All patients received anti-interleukin-2 receptor antibodies, cyclosporine A, and corticosteroids. A planned 3-month analysis from this 12-month study is presented here.
One hundred and thirty-nine patients were randomized (IE 65, DE 74). The primary composite endpoint: biopsy-proven acute rejection, graft loss, death, DGF, wound healing events, or lost to follow-up at month 3, occurred in 36 IE patients (55.4%) and 47 DE patients (63.5%, P=0.387). The incidence of DGF was similar between groups (IE 24.6%, DE 24.3%; n.s.). Wound healing events of any type occurred in 40.0% and 41.9% of IE and DE patients (n.s.); events relating to initial transplant surgery occurred in 36.9% IE patients and 37.8% DE patients (n.s.), most of which were fluid collections. Study drug was discontinued due to adverse events or graft loss in 13 IE (20.0%) and 17 DE patients (23.0%).
Findings from this randomized, multicenter trial indicate that kidney function recovery, wound healing, efficacy, and tolerance are similar at 3 months posttransplant with immediate or DE in patients at protocol-specified risk of DGF.
Transplantation 08/2009; 88(1):69-76. · 4.00 Impact Factor
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ABSTRACT: To report our experience with 9 consecutive laparoscopic radical prostatectomy (LRP) on renal transplant recipients (RTR) and to compare it with other LRPs performed during the same period by the same surgeons. Retropubic radical prostatectomy has widely been described in RTR, whereas LRP has rarely been studied.
Between January 2007 and December 2008, all clinical data from patients undergoing radical prostatectomy were prospectively collected in a database. The database was searched to find information of LRP on RTR. We compared RTR and other patients for all relevant clinical data and for surgical complications.
A total of 9 LRP on RTR (5.8%) and other 164 LRP were performed. LRP on RTR were compared with other LRP. No statistically relevant difference was observed in patient characteristics, biopsy core pathologic analysis, prostate specimen pathologic analysis, and oncologic outcomes. Surgical procedure was also achieved under the same conditions in RTR than in other patients (surgical time, blood loss, transfusion rate, bladder injury). Rectal injury rate was significantly higher in RTR than in other patients (22.2% vs 1.8%, P = .022).
LRP in RTR is feasible. The procedure can be managed the same way as LRP on other patients, but special care must be taken to avoid rectal injury. In our experience, the dissection of the posterior side of the prostate was more difficult on RTR than on other patients.
Urology 08/2009; 74(3):683-7. · 2.43 Impact Factor
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Christian Noël,
Daniel Abramowicz,
Dominique Durand,
Georges Mourad,
Philippe Lang,
Michèle Kessler,
Bernard Charpentier,
Guy Touchard,
François Berthoux, Pierre Merville,
Nacera Ouali,
Jean-Paul Squifflet,
François Bayle,
Karl Martin Wissing,
Marc Hazzan
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ABSTRACT: Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival.
Journal of the American Society of Nephrology 07/2009; 20(6):1385-92. · 9.66 Impact Factor
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ABSTRACT: Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation. Over the last decade, MMF has also emerged as an alternative therapeutic regimen for autoimmune diseases, mainly for patients refractory to other therapies. The active compound of MMF, mycophenolic acid (MPA), depletes the intracellular pool of guanosine tri-phosphate through inosine monophosphate dehydrogenase blockade. The molecular mechanism involved in the elimination of T and B lymphocytes upon inhibition of inosine monophosphate dehydrogenase remains elusive. In this study, we showed that in contrast to the immunosuppressors azathioprine, cyclosporin A, and tacrolimus, MPA killed lymphocytes through the activation of a caspase-independent necrotic signal. Furthermore, the MPA-mediated necrotic signal relied on the transmission of a novel intracellular signal involving Rho-GTPase Cdc42 activity and actin polymerization. In addition to its medical interest, this study sheds light on a novel and atypical molecular mechanism leading to necrotic cell death.
The Journal of Immunology 01/2009; 181(11):7630-8. · 5.79 Impact Factor
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Transplant International 12/2008; 22(5):586-7. · 2.92 Impact Factor
