RESUMO
BACKGROUND: Renal allograft survival is negatively affected by the development of de novo posttransplant donor-specific antibodies (dnDSA). We sought to determine whether treatment with intravenous immunoglobulin (IVIG) could remove or reduce the intensity of dnDSA. METHODS: A single-center study of 12 recipients with dnDSA and stable function who received IVIG 1 g/kg monthly for 6 months were compared with a contemporaneous cohort of 24 recipients with dnDSA who did not receive IVIG. RESULTS: The median time to first dnDSA was 6 months (interquartile range [IQR], 1-12), and follow-up was 83 months (IQR, 58-94) posttransplant. Resolution of dnDSA occurred in 27% of IVIG vs 46% of control recipients (P = .48). Fifty-eight percent of recipients in both cohorts demonstrated a reduction in the intensity of the dominant DSA at last follow-up (P =1.0). A reduction in the number of dnDSAs occurred in 58% vs 62% of the IVIG and control cohorts, respectively (P = .81). Post-dnDSA, acute rejection occurred in 8% of the IVIG vs 42% in the control group (P = .06). Forty-two percent of IVIG-treated vs 49% of control recipients had a deterioration in function from first dnDSA until most recent follow-up (P = .81). Actuarial graft survivals were equivalent between groups. CONCLUSIONS: IVIG treatment of dnDSA in recipients with stable graft function had no impact on DSA clearance or MFI reduction, but this outcome may also be owing to sample size. Larger studies or alternate dosing regimens may be required to determine if there is any role for the use of IVIG as a treatment for dnDSA.
Assuntos
Transplante de Rim , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Imunoglobulinas Intravenosas , Isoanticorpos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , TransplantadosRESUMO
BACKGROUND The pharmacokinetics and metabolism of tacrolimus, an immunosuppressant commonly used to prevent transplant rejection, can differ in specific subpopulations. This analysis examined treatment outcomes and safety of immediate-release tacrolimus (IR-Tac) and LCP-tacrolimus (LCPT) in stable Hispanic kidney transplant recipients. MATERIAL AND METHODS This was a post hoc analysis of clinical trial data from Hispanic adult stable kidney transplant recipients randomized to remain on IR-Tac or convert from IR-Tac to a reduced dose of LCPT (NCT00817206). Composite treatment failure was evaluated at 12 months. Estimated glomerular filtration rate and tacrolimus trough concentrations were evaluated over 12 months. RESULTS Fifty-five stable (LCPT n=26, IR-Tac n=29) kidney transplant recipients who self-identified as Hispanic or Latino were included in this analysis. Composite treatment failure occurred in 1 patient (4%) who converted to LCPT and 1 (3%) who remained on IR-Tac. The estimated glomerular filtration rate was stable over time and similar in the 2 treatment groups (P=0.08). Tacrolimus trough levels for both groups were similar over time in the 2 treatment groups (P=0.98). Treatment-emergent adverse events were similar in patients who converted to LCPT and in those who remained on IR-Tac. CONCLUSIONS Efficacy and safety were similar in Hispanic kidney transplant recipients who converted from IR-Tac to LCPT and in those remaining on IR-Tac.
Assuntos
Imunossupressores , Transplante de Rim , Tacrolimo , Adulto , Esquema de Medicação , Feminino , Rejeição de Enxerto/prevenção & controle , Hispânico ou Latino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , TransplantadosRESUMO
Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.
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In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.
Assuntos
Vírus BK , Ciprofloxacina/uso terapêutico , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Infecções por Polyomavirus/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/prevenção & controle , Estudos Prospectivos , Resultado do Tratamento , Infecções Tumorais por Vírus/prevenção & controle , Viremia/prevenção & controleRESUMO
BACKGROUND: Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. METHODS: We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. RESULTS: Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. CONCLUSION: UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.
Assuntos
Febre/tratamento farmacológico , Febre/etiologia , Metilprednisolona/uso terapêutico , Transplante de Pâncreas/efeitos adversos , Complicações Pós-Operatórias , Adulto , Gerenciamento Clínico , Feminino , Febre/patologia , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. METHODS: In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. RESULTS: At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. CONCLUSION: Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function.
Assuntos
Infecções por Citomegalovirus/prevenção & controle , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Infecções por Polyomavirus/prevenção & controle , Infecções Tumorais por Vírus/prevenção & controle , Viremia/prevenção & controle , Adulto , Vírus BK/efeitos dos fármacos , Vírus BK/isolamento & purificação , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/uso terapêutico , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Viremia/epidemiologia , Viremia/virologia , Adulto JovemRESUMO
Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction.
Assuntos
Abatacepte/farmacologia , Soro Antilinfocitário/farmacologia , Infecções por HIV/complicações , Imunossupressores/farmacologia , Transplante de Rim , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. METHODS: A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA. RESULTS: Of 708 recipients, 22% developed dnDSA, of whom 64% had persistent dnDSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dnDSA vs the persistent dnDSA group (2% vs 22%; P<.001,) and fewer graft losses with isolated dnDSA vs persistent dnDSA (0% vs 10%; P=.03). Within the persistent dnDSA group, recipients with dnDSA ≥60% of time points, had more AR (32% vs 16%, P=.10) and more graft losses (21% vs 2%; P=.003) than those with dnDSA<60%. CONCLUSIONS: Persistence of dnDSA resulted in more AR and graft failure than a single positive value. Recipients with longer duration of dnDSA persistence had an additional increased risk of AR and graft failure.
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Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Rim , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups.
Assuntos
Soro Antilinfocitário/uso terapêutico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Transplante de Rim , Adulto , Negro ou Afro-Americano , Anticorpos/imunologia , Feminino , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Falência Renal Crônica/etnologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted.
Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Viremia , Humanos , Incidência , Estudos RetrospectivosRESUMO
BACKGROUND: Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation. METHODS: A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis. RESULTS: One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2-444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis. CONCLUSION: The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.
Assuntos
Acessibilidade aos Serviços de Saúde , Transplante de Rim/métodos , Adulto , Interpretação Estatística de Dados , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/terapia , Encaminhamento e Consulta , Diálise Renal , Inquéritos e Questionários , Fatores de TempoRESUMO
Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by "indirect" viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed "breakthrough" viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.
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BACKGROUND: Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. METHODS: The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. RESULTS: Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). CONCLUSIONS: Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.
Assuntos
Anticorpos/imunologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Transplante de Rim , Doadores de Tecidos , Transplante , Adulto , Anticorpos/sangue , População Negra , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto/etnologia , Hispânico ou Latino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transplante de Pâncreas , Fatores de Risco , Fatores de Tempo , População BrancaRESUMO
The response to allografting involves adaptive and innate immune mechanisms. In the adaptive system, activated T cells differentiate to cytotoxic effectors that attack the graft and trigger B cells to differentiation to plasma cells that produce anti-HLA antibodies. The innate immune system recognizes antigens in a non-specific manner and recruits immune cells to the graft through the productions of chemotactic factors, and activation of cytokines and the complement cascade. In the kidney the tubules and the endothelium are the targets of the rejection response. Immune suppression is effective in modulating the adaptive immune system effect on graft histology.
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Tolerância Imunológica/imunologia , Transplante de Rim , Imunologia de Transplantes , Aloenxertos , Vírus BK , Inibidores de Calcineurina , Citocinas/imunologia , Cirurgia Geral , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunidade Inata , Imunossupressores/uso terapêutico , Infecções por Polyomavirus , Linfócitos T/imunologia , Infecções Tumorais por VírusAssuntos
Vírus BK/isolamento & purificação , Imunossupressores/efeitos adversos , Nefropatias/prevenção & controle , Transplante de Rim/imunologia , Programas de Rastreamento , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Viremia/diagnóstico , Feminino , Humanos , MasculinoRESUMO
Anti-Xa monitoring for low molecular weight heparin (LMWH) is currently recommended in obese, renally impaired, and pregnant patients. Substantial evidence indicates that solid organ transplant (SOT) patients are at an increased risk of renal impairment, thus representing a population at risk of LMWH accumulation. The purpose of this study was to review our experience with LMWH dosing and monitoring in a cohort of transplant recipients. This was a retrospective, single-center review of 96 SOT patients receiving enoxaparin treatment and anti-Xa monitoring. The percent of patients with supratherapeutic anti-Xas (>1 IU/mL) was determined, as was the relationship between enoxaparin dosages and anti-Xa levels and bleeding. The cohort had a mean age of 62 yr and creatinine clearance of 59 mL/min and was primarily lung transplant recipients (73%). The mean enoxaparin dose was 0.82 mg/kg, which resulted in a mean anti-Xa level of 0.98 IU/mL. Despite the reduced enoxaparin dose, 44% of patients experienced a supratherapeutic anti-Xa level. Patients with supratherapeutic anti-Xas had higher doses than those within the therapeutic range (0.89 mg/kg vs. 0.77 mg/kg; p = 0.002). No major bleeds occurred. Supratherapeutic anti-Xa levels are common in transplant patients receiving enoxaparin therapy. Empirically reduced dosing of enoxaparin and monitoring may warrant consideration in this population.
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Anticoagulantes/administração & dosagem , Monitoramento de Medicamentos , Fator Xa/análise , Heparina de Baixo Peso Molecular/administração & dosagem , Transplante de Órgãos , Adulto , Idoso , Anticoagulantes/análise , Enoxaparina/uso terapêutico , Feminino , Seguimentos , Heparina de Baixo Peso Molecular/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
The pharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations. The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400 mg/day of phenytoin for two to three days. Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects. Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity.
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BACKGROUND: This study reviewed the outcomes of a screening protocol for BK viremia to determine if early diagnosis, followed by immunosuppression minimization, would prevent progression to nephropathy and graft loss. METHODS: This review included 369 renal transplant recipients tested for BK virus at serial time points after transplantation. Management included immunosuppression minimization plus cidofovir treatment for BK nephropathy. RESULTS: Recipients received tacrolimus-based immunosuppression, with 8% prednisone-free and 6% who received desensitization. With a mean follow-up of 22 ± 10 months, 16% (n = 57) of recipients became BK viremia positive. The median (range) time to diagnosis was 3 (1-17) months. Because renal biopsy was performed selectively, 59% of recipients underwent biopsy, with 47% showing BK nephropathy. Seventy-four percent of recipients cleared the virus at a median (range) time of 9 (3-33) months, with four grafts lost to BK nephropathy. Cidofovir-treated recipients displayed a higher viral load at diagnosis but showed equivalent renal function at last evaluation. In multivariate analysis, recipient age, Asian ethnicity, deceased donor, and prednisone use were factors independently associated with BK viremia. Actuarial survival of BK-positive grafts was worse than that of BK-negative grafts (P<0.01, log-rank test). At 9 and 12 months, the mean estimated glomerular filtration rate of the BK-positive group was lower than that of the BK-negative cohort (P = 0.02). CONCLUSIONS: Despite using a screening protocol combined with immunosuppression minimization, BK-positive recipients had a greater risk of graft loss and impaired function than recipients free of infection. Future investigations should focus on practices to prevent BK viremia.
Assuntos
Vírus BK/isolamento & purificação , Imunossupressores/efeitos adversos , Nefropatias/prevenção & controle , Transplante de Rim/imunologia , Programas de Rastreamento , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Viremia/diagnóstico , Adulto , Antivirais/uso terapêutico , Vírus BK/genética , Biópsia , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapêutico , Diagnóstico Precoce , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Nefropatias/diagnóstico , Nefropatias/imunologia , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Análise Multivariada , Organofosfonatos/uso terapêutico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Texas , Fatores de Tempo , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Carga Viral , Viremia/imunologia , Viremia/virologia , Adulto JovemRESUMO
Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo. After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ-only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92-94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.
Assuntos
Antígenos HLA-DQ/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim/imunologia , Doadores de Tecidos , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Creatinina/sangue , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/imunologia , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Antígenos HLA-DR/imunologia , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Monitorização Imunológica , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/imunologia , Estudos Retrospectivos , Texas , Fatores de Tempo , Resultado do TratamentoRESUMO
Immunosuppressed solid organ transplant recipients are included in the cohort at increased risk for complications of viral infections such as the newly encountered H1N1. A retrospective review was performed to collect data on patients hospitalized during a recent H1N1 epidemic. H1N1 was suspected based on symptoms and real-time reverse-transcriptase-polymerase-chain-reaction assay confirmed the diagnosis. From August through October of 2009, 89 patients were admitted to The Methodist Hospital, Houston, Texas, with H1N1. Eighteen were solid organ transplant recipients with an age range of 34-69 yr. This group included nine kidney, five lung, one kidney-pancreas, one liver, and two heart recipients. Severe cardiac or pulmonary comorbidities existed in over half of non-transplant patients, while only eight of these non-transplant patients were otherwise healthy. Eighty-nine percent of transplant patients presented with fever or chills, 72% with cough, and 56% with gastrointestinal distress. Symptoms were similar to non-transplant patients. All transplant patients were treated with oseltamivir. Two non-transplant patients and three transplant patients died. Thirty-day survival was 97% in non-transplant and 83% in transplant patients (p=0.02). In the context of an initial epidemic of H1N1, infection was associated with increased risk of complications and mortality in solid organ transplant recipients.