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1.
J Infect Dis ; 220(5): 761-771, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31157865

RESUMO

BACKGROUND: Rabbit antithymocyte globulin (rATG) induction is associated with profound immunosuppression, leading to a higher risk of cytomegalovirus (CMV) infection compared with anti-interleukin 2 receptor antibody (anti-IL-2RA). However, this risk, depending on the baseline CMV serological recipient/donor status, is still controversial. METHODS: The CMV DNAemia-free survival between rATG- and anti-IL-2RA-treated patients was analyzed in donor-positive/recipient-negative (D+R-) and recipient-positive (R+) patients in 1 discovery cohort of 559 kidney transplant recipients (KTRs) and 2 independent cohorts (351 and 135 kidney KTRs). The CMV-specific cell-mediated immunity (CMI) at baseline and at different time points after transplantation was assessed using an interferon γ enzyme-linked immunosorbent spot assay. RESULTS: rATG increased the risk of CMV DNAemia in R+ but not in D+R- KTRs. In R+ CMI-positive (CMI+) patients, the CMV DNAemia rate was higher in rATG-treated than in anti-IL-2RA-treated patients; no difference was observed among R+ CMI-negative (CMI-) patients. Longitudinal follow-up demonstrated a deeper depletion of preformed CMV CMI in R+ rATG-treated patients. CONCLUSIONS: D+R- KTRs have the highest risk of CMV DNAemia, but rATG adds no further risk. Among R+ KTRs, we described 3 groups, the least prone being R+CMI+ KTRs without rATG, then R+CMI+ KTRs with rATG, and finally R+CMI- KTRs. CMV serostatus, baseline CMV-specific CMI, and induction therapy may lead to personalized preventive therapy in further studies.

2.
Eur J Radiol ; 117: 209-215, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31221527

RESUMO

OBJECTIVES: To evaluate the performance of dynamic contrast-enhanced MRI measurement of glomerular filtration rate (GFR) compared with the reference standard technique of urinary clearance of 51Cr-EDTA. PATIENTS AND METHODS: All kidney transplant recipients (KTRs) with an indication for non-urgent contrast-enhanced MRI at our institution were prospectively included between 2008 and 2012. Renographies were acquired by low-dose dynamic contrast-enhanced MRI (DCE-MRI) then fitted with a two-compartment pharmacokinetic model. MR-GFR was compared with reference isotopic measurements using Bland-Altman diagrams, intraclass correlation coefficient (ICC) and concordance rates. RESULTS: Forty-two KTRs (mean age 51.5 years, 26-74) were analyzed. Mean estimated GFR was 48.5 ± 27 mL/min/1.73m2 (24-178 mL/min). The mean bias was +13.2 mL/min (6.4-20.0, +36.9%) ranging from -31.0 mL/min (-41.7%) to +101.4 mL/min (+89.2%) with a large variability (standard-deviation: 22.3 mL/min; limits of agreement: [-30.6 (-43.3--18.9); +57.0 (45.3-68.7)]). The ICC was 0.32 (0.02-0.56) and the concordance rate was 28.6% (14.9-42.2). CONCLUSIONS: The large variability of MR-GFR compared with the reference technique precludes its use in KTRs, whose anatomical peculiarities make standardization of arterial input function (AIF) difficult.


Assuntos
Radioisótopos de Cromo/farmacocinética , Ácido Edético/farmacocinética , Transplante de Rim , Imagem por Ressonância Magnética , Transplantados , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Proc Natl Acad Sci U S A ; 116(24): 11906-11915, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31118283

RESUMO

γδ T lymphocytes represent ∼1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify γδ T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their T cell receptor (TCR)Vδ1 and TCRVδ2 subsets in large datasets from complex cell mixtures. In t-distributed stochastic neighbor embedding plots from blood and tumor samples, the few γδ T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVδ1 and TCRVδ2 subsets form close yet distinct subclusters, respectively neighboring NK and CD8 T cells because of expression of shared and distinct cytotoxic maturation genes. Similar pseudotime maturation trajectories of TCRVδ1 and TCRVδ2 γδ T lymphocytes were discovered, unveiling in both subsets an unattended pool of terminally differentiated effector memory cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single-cell transcriptomes of thousands of individual γδ T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping, and deep characterization of human γδ T lymphocytes in further scRNA-seq studies of complex tissues in physiological and disease conditions.

5.
Kidney Int ; 96(1): 231-244, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31027892

RESUMO

This is a randomized trial (ATHENA study) in de novo kidney transplant patients to compare everolimus versus mycophenolic acid (MPA) with similar tacrolimus exposure in both groups, or everolimus with concomitant tacrolimus or cyclosporine (CsA), in an unselected population. In this 12-month, multicenter, open-label study, de novo kidney transplant recipients were randomized to everolimus with tacrolimus (EVR/TAC), everolimus with CsA (EVR/CsA) or MPA with tacrolimus (MPA/TAC), with similar tacrolimus exposure in both groups. Non-inferiority of the primary end point (estimated glomerular filtration rate [eGFR] at month 12), assessed in the per-protocol population of 338 patients, was not shown for EVR/TAC or EVR/CsA versus MPA/TAC. In 123 patients with TAC levels within the protocol-specified range, eGFR outcomes were comparable between groups. The mean increase in eGFR during months 1 to 12 post-transplant, analyzed post hoc, was similar with EVR/TAC or EVR/CsA versus MPA/TAC. The incidence of treatment failure (biopsy proven acute rejection, graft loss or death) was not significant for EVR/TAC but significant for EVR/CsA versus MPA/TAC. Most biopsy-proven acute rejection events in this study were graded mild (BANFF IA). There were no differences in proteinuria between groups. Cytomegalovirus and BK virus infection were significantly more frequent with MPA/TAC. Thus, everolimus with TAC or CsA showed comparable efficacy to MPA/TAC in de novo kidney transplant patients. Non-inferiority of renal function, when pre-specified, was not shown, but the mean increase in eGFR from month 1 to 12 was comparable to MPA/TAC.

6.
Kidney Int ; 95(6): 1471-1485, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30955869

RESUMO

Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.

8.
Front Immunol ; 10: 235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906289

RESUMO

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9-indicative of complement-mediated injury-is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25-73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9- ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients.

9.
J Am Soc Nephrol ; 30(4): 692-709, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850439

RESUMO

BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed. METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs. RESULTS: We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals. CONCLUSIONS: Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.

10.
Kidney Int ; 95(4): 896-904, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30819555

RESUMO

While direct measurements of glomerular filtration rate (GFR) provide the most accurate evaluation of pre-donation kidney function, guidelines do not systematically require the use of a reference method. We evaluated whether and to what extent relying upon creatinine-based estimating equations (eGFR) rather than direct measurement of GFR (mGFR) alters the selection of potential living donors. We compared the impact of 4 equations (the MDRD study equation, the CKD-EPI equation, the revised Lund-Malmö equation, and the full age spectrum [FAS] equation) on the evaluation of 2733 potential donors with GFR measured by reference methods. We also considered the impact of using either absolute or age-adapted GFR thresholds. The CKD-EPI and FAS equations had the best performances (P10 of 50.6% and 47.8%; P30 of 94.4% and 93.1%, respectively) and led to the lowest proportion of improperly evaluated candidates. Misclassification was more frequent when GFR adequacy was defined as an absolute threshold of 90 ml/min/1.73m2 as compared to an age-adapted definition (26% and 5%, respectively). Interpretation of eGFR according to an absolute threshold of 90 ml/min/1.73m2 identified 1804 candidates eligible to donate, compared to 2648 when mGFR was interpreted with age-adapted thresholds. We conclude that creatinine-based estimates cannot substitute for direct GFR measurement to evaluate candidates for kidney donation. When reference methods for direct GFR measurement are not available, our data suggest that a strategy based on age-adapted eGFR values estimated with either the CKD-EPI or FAS equation should be preferred.

11.
Kidney Int ; 94(3): 616-624, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30143068

RESUMO

Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m2. Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process.

13.
Nature ; 558(7711): 540-546, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29899452

RESUMO

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

14.
Biosens Bioelectron ; 117: 191-200, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29902635

RESUMO

Human leukocyte antigen (HLA) donor-specific antibodies are key serum biomarkers for assessing the outcome of transplanted patients. Measuring their active concentration, i.e. the fraction that really interacts with donor HLA, and their affinity could help deciphering their pathogenicity. Surface plasmon resonance (SPR) is recognized as the gold-standard for measuring binding kinetics but also active concentrations, without calibration curves. SPR-based biosensors often suffer from non-specific binding (NSB) occurring with the sensor chip surface and the immobilized targets, especially for complex media such as human serum. In this work we show that several serum treatments such as dialysis or IgG purification reduce NSB but insufficiently for SPR applications. We then demonstrate that the NSB contribution to the SPR signal can be eliminated to determine precisely and reliably the active concentration and the affinity of anti-HLA antibodies from patients' sera. This was achieved even at concentrations close to the limit of quantification of the method, in the 0.5-1 nM range. The robustness of the assay was demonstrated by using a wide range of artificially generated NSB and by varying the density of the targets captured onto the surface. The assay is of general interest and can be used with molecules generating strong NSB, as far as a non-cognate target structurally close to the target can be captured on the same flow cell, in a different binding cycle. Compared with current fluorescence-based methods that are semi-quantitative, we expect this SPR-based assay to help better understanding anti-HLA antibodies pathogenicity and improving organ recipients' management.

16.
Am J Transplant ; 18(12): 2945-2954, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29745007

RESUMO

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive 5 doses of ASP0113 (5 mg; n = 75) or placebo (n = 74) on Days 30/60/90/120/180 posttransplant, and they received prophylactic valganciclovir/ganciclovir 10-100 days posttransplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after the first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; P = .307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. ClinicalTrials.gov registration number: NCT01974206.

17.
Nephrol Dial Transplant ; 33(12): 2245-2252, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846692

RESUMO

Background: It is recommended to determine the risks of end-stage renal disease (ESRD) in living donor candidates. The aim of this study was to determine how many candidates would have been cleared for donation according to different thresholds of risks. Methods: Four pre-donation and post-donation risks of ESRD were calculated retrospectively using online tools (http://www.transplantmodels.com/) and the calculator of the University of Minnesota for 151 living kidney donors and 27 patients disqualified for living donation based on a glomerular filtration rate (GFR) <80 mL/min/1.73 m2. Results: A complete overlap of the pre-donation 15-year ESRD risk, pre-donation projected lifetime ESRD risk, post-donation 15-year ESRD risk and the Minnesota post-donation 15-year risk of ESRD or GFR <30 mL/min/1.73 m2 was observed for the living kidney donors and the disqualified candidates. We next defined different thresholds of pre- and post-donation risks of ESRD that could be used for clearing living donation. In candidates over 61 years of age, the use of a pre-donation 15-year ESRD risk of 0.25% and/or a post-donation 15-year ESRD risk of 50 per 10 000 would increase the percentage of donors by 28.6% and 26.3%, respectively. Conversely, only 22.3% of donors aged 18-35 years would have been selected by using a pre-donation projected lifetime ESRD risk <0.5%. Conclusions: The use of these ESRD risks would significantly modify donor selection by increasing the percentage of donors ≥61 years of age with GFR <80 mL/min/1.73 m2 and by decreasing the percentage of donors aged 18-35 years with a high GFR.

18.
Nephrol Dial Transplant ; 33(10): 1853-1863, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29672702

RESUMO

Background: Pathogenicity of donor-specific antibodies (DSAs) can be assessed using the single-antigen flow beads (SAFB) assays through mean fluorescence intensity (MFI) with or without serum ethylenediaminetetraacetic acid (EDTA) treatment, measurement of C1q or C3d binding and/or their intragraft detection [graft-bound donor-specific antibody (gDSA)]. We aimed to investigate which of these markers best associates with antibody-mediated rejection (ABMR) and kidney allograft loss at the time of a for-cause biopsy. Methods: This retrospective, single-centre study included 77 kidney transplant recipients who underwent a for-cause biopsy between December 2004 and July 2013. All displayed serum DSAs were identified on the same day as the biopsy. Sera were tested in parallel with the classical SAFB assay with or without serum EDTA treatment, C1q- and C3d-binding assays. gDSAs were eluted from biopsy fragments and identified with SAFB. Results: The median time between transplantation and biopsy was 25 months (range 0.5-251). The median follow-up was 36 months (range 0-140). ABMR was histologically proven in 40% of recipients. The sensitivity and specificity of C1q, C3d and gDSA assays for predicting ABMR were 68% and 61%, 52% and 70% and 64.5% and 56.5%, respectively. At the time of biopsy, only the DSA MFI after EDTA treatment and C3d positivity were associated with graft loss. In multivariate analyses, glomerular filtration rate, transplant glomerulopathy and C4d positivity were the only factors associated with graft loss. Conclusions: Our findings weaken the rationale for systematically implementing C1q, C3d or gDSA assays in this situation, because they do not independently predict ABMR and graft loss.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29579221

RESUMO

Background: Kidney transplantation (KT) is the treatment of choice for end-stage renal disease. Preemptive KT (PKT) should be considered when glomerular filtration rate is <15 mL/min/1.73 m2 but European reports on the results of PKT and the effect of pretransplant dialysis are scarce. Methods: We analysed all first kidney-only transplants performed in adults in France between 2002 and 2012. A Cox multivariable model was used to investigate the association of PKT and of pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis or retransplant, whichever occurred first. Results: We included 22 345 patients, with a mean ± SD age at KT of 50.5 ± 13.4 years; 61.9% were men and 3112 (14.0%) received a PKT. Median time of follow-up was 4.7 years. Graft failure occurred in 4952 patients up to 31 December 2013. After adjustment for recipients' age and sex, primary kidney disease, donor type (living or deceased donor, expanded criteria donor), HLA mismatches, cold ischaemia time, centre and year of transplantation, PKT was associated with a decreased hazard of graft failure when compared with pretransplant dialysis [hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.51-0.63], whatever the duration of dialysis, even in the first 6 months. The effect of PKT on the hazard of graft failure was stronger in living kidney donors (HR 0.32; 95% CI 0.19-0.55). Conclusions: In France, PKT was associated with a lower risk of graft failure than KT performed after the initiation of dialysis, whatever the duration of dialysis.

20.
Clin J Am Soc Nephrol ; 12(10): 1663-1670, 2017 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-28818847

RESUMO

BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorders arising after kidney transplantation portend an increased risk of morbidity and mortality. Retransplantation of patients who had developed post-transplant lymphoproliferative disorder remains questionable owing to the potential risks of recurrence when immunosuppression is reintroduced. Here, we investigated the feasibility of kidney retransplantation after the development of post-transplant lymphoproliferative disorder. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed the data from all patients who underwent kidney retransplantation after post-transplant lymphoproliferative disorder in all adult kidney transplantation centers in France between 1998 and 2015. RESULTS: We identified a total of 52 patients with kidney transplants who underwent 55 retransplantations after post-transplant lymphoproliferative disorder. The delay from post-transplant lymphoproliferative disorder to retransplantation was 100±44 months (28-224); 98% of patients were Epstein-Barr virus seropositive at the time of retransplantation. Induction therapy for retransplantation was used in 48 patients (i.e., 17 [31%] patients received thymoglobulin, and 31 [57%] patients received IL-2 receptor antagonists). Six patients were also treated with rituximab, and 53% of the patients received an antiviral drug. The association of calcineurin inhibitors, mycophenolate mofetil, and steroids was the most common maintenance immunosuppression regimen. Nine patients were switched from a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. One patient developed post-transplant lymphoproliferative disorder recurrence at 24 months after retransplantation, whereas post-transplant lymphoproliferative disorder did not recur in 51 patients. CONCLUSIONS: The recurrence of post-transplant lymphoproliferative disorder among patients who underwent retransplantation in France is a rare event.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/cirurgia , Adulto , Idoso , Substituição de Medicamentos , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , França , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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