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BACKGROUND: Renal transplant recipients with donor-specific anti-HLA antibodies are at an increased risk of antibody-mediated rejection (AMR). Early protocolized renal biopsies may serve as a strategy to improve diagnosis in this patient population. METHODS: We evaluated 155 highly sensitized renal transplant recipients with cPRA class I + II > 90% pre-transplant from 2015 to 2022. Patients with protocol biopsies within the first two weeks post-transplant were included. RESULTS: A total of 122 patients were included in the study. Of these, 13 (10.6%) were diagnosed with very early antibody-mediated rejection (veABMR) within the first two weeks post-transplant. This corresponds to 52% (13/25 patients) of all ABMR cases reported during the follow-up of this population. The graft survival rates at one and three years were significantly lower in patients with veABMR (p < 0.001) compared to patients without rejection in the early protocol biopsy. In terms of severity, the veABMR cohort exhibited a hazard ratio (HR) of 10.33 (95% CI 3.23-33.06; p < 0.001) for graft failure. The presence of donor-specific antibodies (DSA) class II on the day of transplantation and a higher percentage of eplet mismatch (EpMM), particularly EpMM DQA1, correlated with the development of veABMR. CONCLUSION: Early protocol biopsies play a pivotal role in the early detection of veABMR in high-risk immunological patients. Patients with veABMR face significant risks of graft loss, despite early treatment of rejection.
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INTRODUCTION: The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002. MATERIALS AND METHODS: We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020. RESULTS: A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively. CONCLUSIONS: MILDN techniques are safe for donors and grafts, with low complication.
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Transplante de Rim , Laparoscopia , Feminino , Humanos , Rim , Transplante de Rim/métodos , Laparoscopia/métodos , Doadores Vivos , Pessoa de Meia-Idade , Nefrectomia/métodos , Estudos Retrospectivos , Coleta de Tecidos e ÓrgãosRESUMO
INTRODUCTION: HLA sensitization is a growing problem in children awaiting kidney transplantation. In some cases, finding an immunologically compatible donor entails contemplating the option of an ABO incompatible transplant or paired transplant. METHODS: Patient with genetic nephrotic syndrome and progressive chronic kidney disease, with a previous thrombosis of a first kidney transplant, resulting hypersensitized and remaining for a long-time on hemodialysis. Despite a desensitization strategy, family members were incompatible and deceased donation options must be ruled out due to the presentation of donor-specific antibodies (DSA). After 4 years, the possibility arises to perform a kidney paired transplant with a 62-year-old woman with an incompatible blood group. Although the current cytotoxicity- and cell-based crossmatches were negative, history of DSA were recorded. RESULTS: An intensive ABO and HLA desensitization protocol was performed in order to combat the isohemagglutinin antibodies and on the memory-HLA, based on rituximab, apheresis sessions, and immunoglobulins. Despite the donor being older in terms of pediatric transplantation, the donor-recipient weight difference, and immunological risk, the transplant was completed successfully. Maintenance of titration of up to 1/2 was confirmed after 3 weeks post-transplant (IgM and IgG). Kidney biopsy at 2 weeks and 6 months without signs of rejection. The patient is currently 12 months post-transplant and has not presented any signs of transplant rejection and has proper renal function. CONCLUSIONS: Kidney paired transplantation is an excellent solution for hypersensitized children, and ABO incompatibility can be considered to increase their options to find a good donor, without thereby obtaining worse results.
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Transplante de Rim , Doadores Vivos , Humanos , Criança , Feminino , Pessoa de Meia-Idade , Transplante de Rim/métodos , Incompatibilidade de Grupos Sanguíneos , Sistema ABO de Grupos Sanguíneos , Espanha , Rejeição de EnxertoRESUMO
We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).
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COVID-19/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Transplantados , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
OBJECTIVE: The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome. SUMMARY OF BACKGROUND DATA: Results from donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated. METHODS: We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes. RESULTS: A total of 49 (14.3%) caDBD were accepted for transplantation [median CAT of 5.0 min (IQR 2.5-15.0)]. Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF [OR 1.09 (95% CI, 1.01-1.17)], and the duration of CPR discriminated for EGF [AUC of 0.86 (95% CI, 0.74-0.98)], with a sensitivity and specificity of 100% and 75% at a cutoff of 15âminutes. When evaluated separately, caDBD >15âmin increased over 5 times the risk for EGF [HR 5.80 (95% CI, 1.82-18.56); P = 0.003], and these presented fewer days on the ICU (1.0 vs 3.0 d). CONCLUSION: CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.
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Parada Cardíaca , Transplante de Pâncreas , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Adulto , Morte Encefálica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The dialysis-based definition of Delayed Graft Function (dDGF) is not necessarily objective as it depends on the individual physician's decision. The functional definition of DGF (fDGF, the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week post-transplant), may be more sensitive to reflect recovery after the ischemia-reperfusion injury. We retrospectively analyzed both definitions in 253 deceased donor kidney transplant recipients for predicting death-censored graft failure as primary outcome, using eGFR < 25 ml/min/1.73 m2 as a surrogate end-point for graft failure. Secondary outcome was a composite outcome that included graft failure as above and also patient's death. Median follow-up was 3.22 [2.38-4.21] years. Seventy-nine patients developed dDGF (31.2%) and 127 developed fDGF (50.2%). Sixty-three patients fulfilled criteria for both definitions (24.9%). At multivariable analysis, the two definitions were significantly associated with the primary [HR (95%CI) 2.07 (1.09-3.94), P = 0.026 for fDGF and HR (95%CI) 2.41 (1.33-4.37), P = 0.004 for dDGF] and the secondary composite outcome [HR (95%CI) 1.58 (1.01-2.51), P = 0.047 for fDGF and HR (95%CI) 1.67 (1.05-2.66), P = 0.028 for dDGF]. Patients who met criteria for both definitions had the worst prognosis, with a three-year estimates (95%CI) of survival from the primary and secondary outcomes of 2.31 (2.02-2.59) and 2.20 (1.91-2.49) years for fDGF+/dDGF+, in comparison with the other groups (P < 0.01 for trend). fDGF provides supplementary information about graft outcomes on top of the dDGF definition in a modern series of kidney transplantation.
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Transplante de Rim , Função Retardada do Enxerto , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Doadores de TecidosRESUMO
The main applications of Data Envelopment Analysis (DEA) to medicine focus on evaluating the efficiency of different health structures, hospitals and departments within them. The evolution of patients after undergoing a medical procedure or their response to a given treatment are not generally studied through this programming technique. In addition to the difficulty inherent to the collection of this type of data, the use of a technique that is mainly applied to evaluate the efficiency of decision making units representing industrial and production structures to analyze the evolution of human patients may seem inappropriate. In the current paper, we illustrate how this is not actually the case and implement a decision engineering approach to model kidney transplantation patients as decision making units. As such, patients undergo three different phases, each composed by specific as well as interrelated variables, determining the potential success of the transplantation process. DEA is applied to a set of 12 input and 6 output variables - retrieved over a 10-year period - describing the evolution of 485 patients undergoing kidney transplantation from living donors. The resulting analysis allows us to classify the set of patients in terms of the efficiency of the transplantation process and identify the specific characteristics across which potential improvements could be defined on a per patient basis.
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Tomada de Decisão Clínica , Transplante de Rim/estatística & dados numéricos , Modelos Estatísticos , Fatores Etários , Diabetes Mellitus , Eficiência Organizacional , Rejeição de Enxerto/epidemiologia , Histocompatibilidade , Humanos , Hipertensão , Transplante de Rim/efeitos adversos , Doadores Vivos , Diálise Renal/estatística & dados numéricos , EspanhaRESUMO
Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.
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COVID-19/epidemiologia , Pacientes Internados , Transplante de Rim , Insuficiência Renal/cirurgia , Medição de Risco/métodos , SARS-CoV-2 , Transplantados , Comorbidade , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologiaRESUMO
INTRODUCTION: Nonantigen-specific immunoadsorption (IA) has proven to be effective in acute antibody-mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig-columns in aAMR. For chronic-active AMR (cAMR), no studies have evaluated the efficacy of nonantingen-specific IA with antihuman Ig-columns. The purpose of this study was to evaluate the role of nonantigen-specific IA with antihuman Ig-columns in the treatment of both aAMR and cAMR in kidney transplantation. MATERIAL AND METHODS: In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen-specific IA with Ig-Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen-specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary. RESULTS: The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow-up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow-up, respectively. For cAMR, mean follow-up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow-up, respectively, although 40% did not respond and required chronic hemodialysis. CONCLUSION: Nonantigen-specific IA with Ig-Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig-Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.
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Rejeição de Enxerto , Sistema Imunitário/imunologia , Imunoglobulina G/imunologia , Transplante de Rim/métodos , Adulto , Idoso , Anticorpos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Imunoglobulinas Intravenosas , Masculino , Pessoa de Meia-Idade , Plasmaferese , Regeneração , Estudos RetrospectivosRESUMO
TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = -0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R- high-risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819.
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Inibidores de Calcineurina/uso terapêutico , Everolimo/uso terapêutico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS: All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS: A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS: Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.
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Morte Encefálica , Sobrevivência de Enxerto , Transplante de Rim/métodos , Rim/fisiopatologia , Modelos Estatísticos , Preservação de Órgãos/normas , Doadores de Tecidos/provisão & distribuição , Adolescente , Adulto , Idoso , Seleção do Doador , Oxigenação por Membrana Extracorpórea , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Tempo , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/normas , Adulto JovemRESUMO
BACKGOUND: In recent years we have witnessed an increase in infections due to multidrug-resistant organisms in kidney transplant recipients (KTR). In our setting, we have observed a dramatic increase in infections caused by extended-spectrum betalactamase-producing (ESBL) Enterobacteriaceae in KTR. In 2014 we changed surgical prophylaxis from Cefazolin 2 g to Ertapenem 1 g. METHODS: We compared bacterial infections and their resistance phenotype during the first post-transplant month with an historical cohort collected during 2013 that had received Cefazolin. RESULTS: During the study period 110 patients received prophylaxis with Cefazolin and 113 with Ertapenem. In the Ertapenem cohort we observed a non-statistically significant decrease in the percentage of early bacterial infection from 57 to 47%, with urine being the most frequent source in both. The frequency of infections caused by Enterobacteriaceae spp. decreased from 64% in the Cefazolin cohort to 36% in the Ertapenem cohort (p = 0.005). In addition, percentage of ESBL-producing strains decreased from 21 to 8% of all Enterobacteriaceae isolated (p = 0.015). After adjusted in multivariate Cox regression analysis, male sex (HR 0.16, 95%CI: 0.03-0.75), cefazolin prophylaxis (HR 4.7, 95% CI: 1.1-22.6) and acute rejection (HR 14.5, 95% CI: 1.3-162) were associated to ESBL- producing Enterobacteriaceae infection. CONCLUSIONS: Perioperative antimicrobial prophylaxis with a single dose of Ertapenem in kidney transplant recipients reduced the incidence of early infections due to ESBL-producing Enterobacteriaceae without increasing the incidence of other multidrug-resistant microorganisms or C. difficile.
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Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefazolina/uso terapêutico , Infecções por Enterobacteriaceae/prevenção & controle , Ertapenem/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resistência beta-LactâmicaRESUMO
Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.
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Inibidores de Calcineurina/administração & dosagem , Everolimo/uso terapêutico , Rejeição de Enxerto/etiologia , Imunossupressores/uso terapêutico , Transplante de Rim , Corticosteroides/uso terapêutico , Adulto , Aloenxertos/fisiopatologia , Ciclosporina/uso terapêutico , Infecções por Citomegalovirus/etiologia , Everolimo/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/patologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/efeitos adversos , Análise de Intenção de Tratamento , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Infecções por Polyomavirus/etiologia , Tacrolimo/uso terapêutico , Infecções Tumorais por Vírus/etiologiaRESUMO
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.
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Aloenxertos/imunologia , Anticorpos/sangue , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transcriptoma , Adulto , Idoso , Aloenxertos/metabolismo , Aloenxertos/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Células Cultivadas , Quimiocina CCL4/genética , Quimiocina CXCL11/genética , Proteínas Inativadoras do Complemento/uso terapêutico , Proteínas do Sistema Complemento/metabolismo , Feminino , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Rim/patologia , Transplante de Rim , Células Matadoras Naturais , Macrófagos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Monócitos , Fenótipo , Troca Plasmática , Receptores de IgG/genéticaRESUMO
Background: Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed. Methods: We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference. Results: Pancreas survival was similar between all groups, but inferior for PAldK when including only those with a functioning graft at day 90 post-transplantation (P = 0.004). Pancreas acute rejection was significantly increased in PAldK (67%; 1.8 ± 1.4 episodes/graft) when compared with PAddK (25%) and SPK (32%) (P < 0.05) patients. In a multivariate Cox regression model including known risk factors for pancreas rejection, PAldK was the only predictor of acute rejection (hazard ratio 6.82, 95% confidence interval 1.51-30.70, P < 0.05). No association was found between donor-recipient HLA mismatches and graft rejection. Repeated HLA mismatches between kidney and pancreas donors (0 versus 1-6) did not correlate with pancreas graft rejection or survival in either PAK transplantation group (P > 0.05). Conclusion: Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.
Assuntos
Sobrevivência de Enxerto , Transplante de Rim/métodos , Transplante de Pâncreas/estatística & dados numéricos , Doadores de Tecidos , Adulto , Idoso , Análise de Variância , Feminino , Rejeição de Enxerto/mortalidade , Humanos , Transplante de Rim/mortalidade , Transplante de Rim/estatística & dados numéricos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Fatores de RiscoRESUMO
Living kidney donors seem highly satisfied with donation. However, previous studies measure satisfaction by a single-item or by simply questioning donors' willingness to donate again or to recommend living donation. With the aim of analyzing whether satisfaction with donation is a multidimensional construct, thus allowing a more specific characterization of dissatisfied donors, 332 living kidney donors (2005-2015) answered a renewed version of the European Living Donation and Public Health Project satisfaction survey. Exploratory factor-analyses suggested that satisfaction was composed of three-factors: violation of donors' expectancies about donation; interference of donation on daily activities, and pain and discomfort. Donors reported high levels of satisfaction. However, cluster-analysis identified a subgroup characterized by a higher discrepancy between the expected and the actually experienced during donation, higher interference on daily activities, and higher pain and discomfort. Most of them considered that hospital discharge was premature, suffered economic losses and perceived worse health outcomes of their recipients. Single questions assessing donors' willingness to donate again or to recommend living donation were unable to differentiate between clusters. In summary, donor's satisfaction seems better characterized by three dimensions than by single questions.
Assuntos
Transplante de Rim/métodos , Doadores Vivos/estatística & dados numéricos , Nefrectomia/psicologia , Satisfação Pessoal , Adulto , Idoso , Feminino , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Chronic active antibody-mediated rejection (c-aABMR) is an important cause of allograft failure and graft loss in long-term kidney transplants. METHODS: To determine the efficacy and safety of combined therapy with rituximab, plasma exchange (PE) and intravenous immunoglobulins (IVIG), a cohort of patients with transplant glomerulopathy (TG) that met criteria of active cABMR, according to BANFF'17 classification, was identified. RESULTS: We identified 62 patients with active c-aABMR and TG (cg ≥ 1). Twenty-three patients were treated with the combination therapy and, 39 patients did not receive treatment and were considered the control group. There were no significant differences in the graft survival between the two groups. The number of graft losses at 12 and 24 months and the decline of eGFR were not different and independent of the treatment. A decrease of eGFR≥13 ml/min between 6 months before and c-aABMR diagnosis, was an independent risk factor for graft loss at 24 months (OR = 5; P = 0.01). Infections that required hospitalization during the first year after c-aABMR diagnosis were significantly more frequent in treated patients (OR = 4.22; P = 0.013), with a ratio infection/patient-year of 0.65 and 0.20 respectively. CONCLUSIONS: Treatment with rituximab, PE, and IVIG in kidney transplants with c-aABMR did not improve graft survival and was associated with a significant increase in severe infectious complications. TRIAL REGISTRATION: Agencia Española de Medicametos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTR-INM-2017-01.
Assuntos
Anticorpos/fisiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Transplante de Rim/efeitos adversos , Troca Plasmática , Rituximab/uso terapêutico , Adulto , Idoso , Terapia Combinada , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Fatores Imunológicos/efeitos adversos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Troca Plasmática/efeitos adversos , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/prevenção & controle , Proteinúria , Estudos Retrospectivos , Rituximab/efeitos adversosRESUMO
There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5-year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66-76) for KDPI <80% (n = 77), 86 (81-90) for KDPI 81-90% (n = 82), and 97 (94-100) for KDPI >91% (n = 205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and death-censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.
Assuntos
Transplante de Rim/mortalidade , Rim/patologia , Doadores de Tecidos , Transplantes/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Função Retardada do Enxerto/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. CONCLUSION: Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.