RESUMO
Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl].
Assuntos
Transplante de Rim , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Doadores Vivos , Estudos RetrospectivosRESUMO
Early graft loss (EGL) is a feared outcome of kidney transplantation. Consequently, kidneys with an anticipated risk of EGL are declined for transplantation. In the most favorable scenario, with optimal use of available donor kidneys, the donor pool size is balanced by the risk of EGL, with a tradeoff dictated by the consequences of EGL. To gauge the consequence of EGL we systematically evaluated its impact in an observational study that included all 10,307 deceased-donor kidney transplantations performed in The Netherlands between 1990 and 2018. Incidence of EGL, defined as graft loss within 90 days, in primary transplantation was 8.2% (699/8,511). The main causes were graft rejection (30%), primary nonfunction (25%), and thrombosis or infarction (20%). EGL profoundly impacted short- and long-term patient survival (adjusted hazard ratio; 95% confidence interval: 8.2; 5.1-13.2 and 1.7; 1.3-2.1, respectively). Of the EGL recipients who survived 90 days after transplantation (617/699) only 440 of the 617 were relisted for re-transplantation. Of those relisted, only 298 were ultimately re-transplanted leading to an actual re-transplantation rate of 43%. Noticeably, re-transplantation was associated with a doubled incidence of EGL, but similar long-term graft survival (adjusted hazard ratio 1.1; 0.6-1.8). Thus, EGL after kidney transplantation is a medical catastrophe with high mortality rates, low relisting rates, and increased risk of recurrent EGL following re-transplantation. This implies that detrimental outcomes also involve convergence of risk factors in recipients with EGL. The 8.2% incidence of EGL minimally impacted population mortality, indicating this incidence is acceptable.
Assuntos
Transplante de Rim , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Rim , Transplante de Rim/efeitos adversos , Países Baixos/epidemiologia , Estudos Retrospectivos , Doadores de Tecidos , Resultado do TratamentoRESUMO
The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m2 at 6 months and 52.5 ± 23.0 ml/min/1.73 m2 at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.
Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Tacrolimo/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Sirolimo/uso terapêuticoRESUMO
PURPOSE: Tacrolimus has a narrow therapeutic window. Measuring trough level (C0) as surrogate for drug exposure (AUC) in renal transplant recipients has limitations. Therefore, limited sampling strategies (LSS's) have been developed. For the newer modified release, once-daily formulation (Tac QD) LSS's are based on either linear regression analysis (LRA) or population pharmacokinetics with maximum a posteriori Bayesian (MAPB) estimation. The predictive performances of both methods were compared, also to LSS's as described in literature. METHODS: LSS's (maximally three sampling time points) were developed for Tac QD from full 24-h sampling by LRA in 27 Caucasian, stable renal transplant recipients. Performance for accuracy (mean absolute prediction error < 10%) and precision (root mean squared error < 15%) was quantified also after MAPB estimation in two independent groups (early and late post-transplant, n = 12 each). RESULTS: LRA determined a single 8 hours post-dose measurement (C8) to fulfil predefined criteria for accuracy (MAPE 3.41%) and precision (RMSE 4.28%). The best LSS contained C2, C8 and C12 for the stable (MAPE 2.42%, RMSE 3.1%) and the early post-transplant group (MAPE 2.46%, RMSE 3.14%). LRA did not include C0 for any LSS, unless it was forced into the model. MAPB estimation showed similar performance. CONCLUSIONS: In renal transplant patients, sampling in the elimination phase (C8) accurately predicted Tac QD exposure, contrary to C0. The 3-point sampling C2, C8 and C12 had the best performance and is also valid early post-transplant. These LSS's were similarly predictive with MAPB estimation. Dried blood spot could facilitate late sampling in clinical practice.
Assuntos
Teorema de Bayes , Monitoramento de Medicamentos/métodos , Modelos Lineares , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Transplantados , Adulto , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.
Assuntos
Rejeição de Enxerto/diagnóstico , Antígenos HLA/imunologia , Histocompatibilidade/imunologia , Imunização/métodos , Falência Renal Crônica/imunologia , Transplante de Rim/efeitos adversos , Seleção de Pacientes , Doadores de Tecidos/provisão & distribuição , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/química , Teste de Histocompatibilidade , Humanos , Isoanticorpos/efeitos adversos , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Obtenção de Tecidos e Órgãos/métodos , Imunologia de TransplantesRESUMO
The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.
Assuntos
Autoanticorpos/imunologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Inibidor beta de Dissociação do Nucleotídeo Guanina rho/imunologia , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Isoanticorpos/imunologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Doadores Vivos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. METHODS: We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. RESULTS: Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). CONCLUSION: These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.
Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto , Terapia de Imunossupressão/métodos , Transplante de Rim , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Rim/imunologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , PrednisolonaRESUMO
BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.
Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/sangue , Adulto , Feminino , Antígenos de Histocompatibilidade Classe I , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Países Baixos , Risco , Doadores de Tecidos , Adulto JovemRESUMO
BACKGROUND: Prospective studies combining physical functioning (PF), physical activity (PA), and body composition (BC) after living donor transplantation/donation are scarce. We aimed to study differences in these parameters between kidney transplant recipients and their living donors by examining changes in these parameters in the first post-operative year in both groups. METHODS: Twenty-two kidney transplant recipients and 22 healthy kidney donors were included in this prospective longitudinal study with a follow-up until twelve months. PF was assessed by handgrip strength (HGS), and by the physical domains of health-related quality of life (HRQOL) using the Short Form-36 questionnaire [PF (SF-36 PF) and physical component summary (PCS) score]. BC was measured by the Body Composition Monitor©, and PA was measured by the SenseWear™ pro3. RESULTS: At baseline, recipients had significantly lower HGS (after adjustment for sex and body weight), SF-36 PF, PCS, and PA, as compared with their donors. In recipients HGS significantly increased in the first year after transplantation, but PA did not change in the first six months after transplantation. Furthermore, no significant increase in lean tissue mass was observed. For healthy donors no significant changes in these parameters were observed, with exception of SF-36 PF, which declined in the first three months after donation, but equaled baseline values after twelve months. CONCLUSION: Recipients showed impressive improvements in PF and the physical domains of HRQOL in the first year after transplantation, reaching levels of healthy kidney donors already three to six months after transplantation. On the contrary, living kidney donation did not show any deterioration of the investigated parameters, supporting little impact for well-screened donors, while there is high benefit for transplant recipients.
Assuntos
Falência Renal Crônica/cirurgia , Doadores Vivos/estatística & dados numéricos , Nefrectomia , Qualidade de Vida , Transplantados/estatística & dados numéricos , Adulto , Composição Corporal , Exercício Físico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Rim/psicologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Nefrectomia/psicologia , Países Baixos , Avaliação de Resultados em Cuidados de Saúde , Desempenho Físico Funcional , Período Pós-OperatórioRESUMO
Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.
Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Complemento C3d/imunologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim/efeitos adversos , Sistema de Registros , Adulto , Distribuição por Idade , Soro Antilinfocitário/imunologia , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Distribuição por Sexo , Doadores de Tecidos , Transplantados/estatística & dados numéricos , Imunologia de TransplantesRESUMO
BACKGROUND: D antigens are not taken into account in the allocation of solid organs. Female transplant recipients with D antibodies as a consequence of D-mismatched kidney transplantation may develop hemolytic disease of the fetus and newborn in future pregnancies. We examined D antibody development in transplant recipients who received D-mismatched kidney transplantation in absence of D prophylaxis and in a setting of reduced immunosuppression. STUDY DESIGN AND METHODS: From 1993 until 2015, a total of 1355 kidney patients received transplantations in our center of whom 156 received a D-mismatched graft. A retrospective analysis was conducted; frozen stored sera obtained from transplant recipients 3 months after transplantation were tested for irregular red blood cell (RBC) antibodies using a three-cell screening and an identification panel. In the case of D antibody positivity, additional testing was performed 1 month before transplantation. RESULTS: In seven of 156 (4.5%) transplant recipients we found irregular RBC antibodies after transplantation, of which five (3.2%) were determined to be D antibodies. We observed only one (0.6%) recipient without D antibodies before transplantation. CONCLUSION: Although the risk of D antibody development is considerably lower after D-mismatched kidney transplantation than D-mismatched pregnancy, anti-D prophylaxis may still be advisable for female transplant recipients of childbearing age.
Assuntos
Terapia de Imunossupressão/métodos , Transplante de Rim , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Imunoglobulina rho(D)/biossíntese , Eritroblastose Fetal/prevenção & controle , Feminino , Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Período Pós-Operatório , Gravidez , Estudos Retrospectivos , Imunoglobulina rho(D)/sangueRESUMO
Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus exposure increases after steroid tapering in many patients. The pregnane X receptor (PXR)-a mediator for CYP3A-has a steroid receptor and might regulate CYP3A5 activity depending on single nucleotide polymorphisms (SNPs) of CYP3A5 or PXR. This may contribute to differences in tacrolimus exposure after steroid tapering. Methods: In a cohort of renal transplant recipients, the influence of CYP3A5 and PXR SNPs (A7635G, C8055T and C25385T) on the dose-normalized Tacrolimus trough concentration (DnC0) and their potential interaction with each other after steroid taper were analysed by linear regression. Eligible were all 83 outpatient renal transplant patients on tacrolimus and steroids in a pharmacokinetic steady state at least 6 weeks after transplantation and whose blood was available for genetic analysis. Results: Compared with the CYP3A5*1/*3 genotype, the CYP3A5*3/*3 SNP showed a significantly stronger increase in DnC0 after steroid taper (+0.29 µg/L/mg; P = 0.002). Of the tested PXR SNPs, PXR G7635G individuals had a significantly stronger increase in DnC0 (compared with A7635A, +0.31 µg/L/mg; P = 0.02), with a weaker increase in A7635G heterozygotes (+0.17 µg/L/mg; P = 0.124). There was neither interaction nor association between CYP3A5 and PXR SNPs. Conclusions: The magnitude of the DnC0 increase due to steroid taper after renal transplantation is related to CYP3A5 SNPs. Independently, the PXR G7635G SNP is related to this increase, proving the role of PXR in tacrolimus metabolism.
Assuntos
Citocromo P-450 CYP3A/genética , Nefropatias/sangue , Transplante de Rim/métodos , Polimorfismo de Nucleotídeo Único/genética , Esteroides/uso terapêutico , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Adulto , Feminino , Genótipo , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Nefropatias/genética , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Receptor de Pregnano X/genética , Estudos Retrospectivos , TransplantadosRESUMO
Background: Delayed graft function (DGF) is a common complication after kidney transplantation in the era of accepting an equal number of brain- and circulatory-death donor kidneys in the Netherlands. To identify those cases with an increased risk of developing DGF, various multivariable algorithms have been proposed. The objective was to validate the reproducibility of four predictive algorithms by Irish et al. (A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant 2010;10:2279-2286) (USA), Jeldres et al. (Prediction of delayed graft function after renal transplantation. Can Urol Assoc J 2009;3:377-382) (Canada), Chapal et al. (A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors. Kidney Int 2014;86:1130-1139) (France) and Zaza et al. (Predictive model for delayed graft function based on easily available pre-renal transplant variables. Intern Emerg Med 2015;10:135-141) (Italy) according to a novel framework for external validation. Methods: We conducted a prospective observational study with data from the Dutch Organ Transplantation Registry (NOTR). Renal transplant recipients from all eight Dutch academic medical centers between 2002 and 2012 who received a deceased allograft were included (N = 3333). The four prediction algorithms were reconstructed from donor, recipient and transplantation data. Their predictive value for DGF was validated by c-statistics, calibration statistics and net benefit analysis. Case-mix (un)relatedness was investigated with a membership model and mean and standard deviation of the linear predictor. Results: The prevalence of DGF was 37%. Despite a significantly different case-mix, the US algorithm by Irish was best reproducible, with a c-index of 0.761 (range 0.756 - 0.762), and well-calibrated over the complete range of predicted probabilities of having DGF. The US model had a net benefit of 0.242 at a threshold probability of 0.25, compared with 0.089 net benefit for the same threshold in the original study, equivalent to correctly identifying DGF in 24 cases per 100 patients (true positive results) without an increase in the number of false-positive results. Conclusions: The US model by Irish et al. was generalizable and best transportable to Dutch recipients with a deceased donor kidney. The algorithm detects an increased risk of DGF after allocation and enables us to improve individual patient management.
Assuntos
Função Retardada do Enxerto/etiologia , Transplante de Rim/efeitos adversos , Modelos Estatísticos , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos , Adolescente , Adulto , Idoso , Função Retardada do Enxerto/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Tempo , Transplante Homólogo , Adulto JovemRESUMO
Kidney biopsy can result in bleeding complications. Prebiopsy testing using bleeding time (BT) is controversial. New whole blood haemostasis tests, such as platelet function analyser-100 (PFA-100) and multiple electrode aggregometry (MEA), might perform better. We postulated that PFA-100 would be suitable to replace BT prebiopsy. In 154 patients, transplanted kidney biopsies were performed after measurement of bleeding time, PFA-100, MEA and mean platelet volume (MPV). Bleeding outcome (haemoglobin (Hb) drop, haematuria (±bladder catheterization), ultrasound finding of a bleeding, need for (non)surgical intervention and/or transfusion) after the biopsy was correlated to each test. Male-female ratio was 2:1. 50% had a surveillance biopsy at either three or 12 months. Around 17% (had) used acetylsalicylic acid (ASA) prebiopsy. Of 17 bleeding events, one subject needed a transfusion. Most bleeding events were Hb reductions over 1 mmol/l and all resolved uneventful. BT, PFA-100, MEA and MPV did not predict a bleeding outcome; prior ASA use however could (odds ratio 3.19; 95%-CI 1.06 to 9.61). Diagnostic performance data and Bland-Altman analysis showed that BT could not be substituted by PFA-100. ASA use was the best determinant of bleeding after kidney biopsy. Routine haemostasis testing prebiopsy has no added value.
Assuntos
Hemorragia/etiologia , Testes de Função Plaquetária , Idoso , Aspirina , Biópsia/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Rim/patologia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Testes ImediatosRESUMO
An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002-2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.
Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos/normas , Fatores Etários , Idoso , Cadáver , Seleção do Doador , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals.
Assuntos
Seleção do Doador , Sobrevivência de Enxerto , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Países Baixos , Risco , Doadores de Tecidos , Transplantados , Resultado do Tratamento , Adulto JovemRESUMO
ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolonged-release tacrolimus-based immunosuppressive regimens. On Days 0-27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolonged-release tacrolimus (≥25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2 ; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2).
Assuntos
Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/imunologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplantados , Resultado do TratamentoRESUMO
BACKGROUND: The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients. We compared the pharmacokinetics (PKs) of Tac ONCE-DAILY in stable kidney transplant recipients under fasted and fed conditions. METHODS: In an open-label, single-center, cross-over PK study, 27 stable kidney white transplant recipients (17 male, 10 female) treated with Tac ONCE-DAILY under fasted conditions were enrolled. Two 10-point 24-hour blood concentration time profiles [area under the blood concentration time curve from time 0 to 24 hours (AUC0-24)] were collected under steady state conditions. The primary objective was to investigate the effect of food on the PKs and relative bioavailability of Tac ONCE-DAILY. RESULTS: Twenty-seven stable renal transplant patients provided 1 AUC0-24 under fasted and fed conditions, respectively. AUC0-24, C24, and Cmax, were lower in the fed state and Tmax was 1 hour postponed. The 90% confidence interval ratio (fed: fasted) for AUC0-24 was 0.81-0.91 and for C24 0.82-0.92 (both P < 0.001). The majority (60%) had no significant change, but the change in AUC0-24 ranged from -38% to +29%. One trough level was below the target range after fed intake. CONCLUSIONS: When Tac ONCE-DAILY is ingested with standard continental breakfast, AUC0-24 and C24 decrease overall, with C24 in the therapeutic range in almost all patients. The convenient fed intake could promote therapy adherence. Given the possible significant change in exposure, we advise monitoring of the tacrolimus trough level 1 week after fed ingestion of Tac ONCE-DAILY.
Assuntos
Desjejum/fisiologia , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Química Farmacêutica/métodos , Estudos Cross-Over , Esquema de Medicação , Feminino , Humanos , Imunossupressores/sangue , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Tacrolimo/sangueRESUMO
In kidney transplantation, donor HLA antibodies are a risk factor for graft loss. Accessibility of donor eplets for HLA antibodies is predicted by the ElliPro score. The clinical usefulness of those scores in relation to transplant outcome is unknown. In a large Dutch kidney transplant cohort, Ellipro scores of pretransplant donor antibodies that can be assigned to known eplets (donor epitope specific HLA antibodies [DESAs]) were compared between early graft failure and long surviving deceased donor transplants. We did not observe a significant Ellipro score difference between the two cohorts, nor significant differences in graft survival between transplants with DESAs having high versus low total Ellipro scores. We conclude that Ellipro scores cannot be used to identify DESAs associated with early versus late kidney graft loss in deceased donor transplants.