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1.
Am J Transplant ; 20(6): 1619-1628, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31887236

RESUMO

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Doadores de Tecidos
2.
Clin Transplant ; 33(9): e13499, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30773688

RESUMO

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the management of transplantation in HIV-infected individuals. Transplantation has become the standard of care for patients with HIV and end-stage kidney or liver disease. Although less data exist for thoracic organ and pancreas transplantation, it is likely that transplantation is also safe and effective for these recipients as well. Despite what is typically a transient decline in CD4+ T lymphocytes, HIV remains well controlled and infection risks are similar to those of HIV-uninfected transplant recipients. The availability of effective directly active antivirals for the treatment of Hepatitis C is likely to improve outcomes in HIV and HCV co-infected individuals, a population previously noted to have decreased survival. Drug interactions remain an important consideration, and integrase inhibitor-based regimens are preferred due to the absence of interactions with calcineurin and mTOR inhibitors. Additionally, despite the use of more potent immunosuppression, rejection rates exceed those found in HIV-uninfected recipients. Ongoing research evaluating HIV-positive organ donors may provide support for utilizing these donors for HIV-positive patients in need of transplantation.


Assuntos
Infecções por HIV/terapia , HIV/isolamento & purificação , Transplante de Órgãos/métodos , Guias de Prática Clínica como Assunto/normas , Doadores de Tecidos/provisão & distribuição , Transplantados/estatística & dados numéricos , Infecções por HIV/virologia , Humanos , Sociedades Médicas
3.
Am J Nephrol ; 38(5): 397-404, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24192457

RESUMO

BACKGROUND: Modern immunosuppression and rabbit antithymocyte globulin (rATG) have facilitated the success of early steroid withdrawal (ESW) protocols. Little data exist on optimal rATG dosing in ESW protocols. METHODS: Rejection at 12 months in era 1 (four doses of rATG, 1.25 mg/kg) vs. era 2 (three doses of rATG, 1.25 mg/kg) was the primary endpoint. Secondary endpoints included patient and graft survival, renal function and infectious complications. Factors associated with rejection at 1 year were identified. RESULTS: 199 patients received rATG induction and ESW: 102 in era 1 and 97 in era 2. Compared to era 1, era 2 was not associated with worse outcomes, including rejection, renal function, infection or graft survival. Rejection at 1 year and uncensored graft survival differed between the dosing groups. Rejection rates were significantly higher in the <4 mg/kg group compared to the 4-5.9-mg/kg and the ≥6-mg/kg groups, whereas uncensored graft survival was the lowest in the ≥6-mg/kg group. Factors associated with rejection at 12 months included: rATG dose received of 4-5.9 versus <4 mg/kg (OR 0.20, 95% CI 0.036-0.85, p = 0.026); recipient age (per year, OR 0.94, 95% CI 0.89-1.0, p = 0.038); panel reactive antibody 10-79.9 versus <10% (OR 5.4, 95% CI 1.2-25, p = 0.030) and rATG dose held (OR 4.0, 95% CI 1.0-15, p = 0.049). CONCLUSIONS: A comparison of rATG dosing based on era did not result in a significant difference in rejection, renal function, infection or graft survival. However, when evaluating the study population based on actual dose received there were notable differences in both rejection rates and uncensored graft survival.


Assuntos
Soro Antilinfocitário/administração & dosagem , Transplante de Rim/métodos , Esteroides/administração & dosagem , Idoso , Animais , Esquema de Medicação , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Coelhos , Insuficiência Renal/terapia , Estudos Retrospectivos , Fatores de Tempo
4.
Clin Transplant ; 23(6): 887-96, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19681971

RESUMO

The long-term use of calcineurin inhibitors (CNI) leads to renal dysfunction in many liver transplant (LT) recipients. The purpose of this analysis is to evaluate renal function in patients converted from CNI to sirolimus (SRL). From May 2002-November 2006, 137 LT were performed in 125 patients, 72 of which were converted to SRL. Evaluation of SRL conversion was stratified by early conversion (<90 d from LT) (EC) vs. late conversion (LC). Renal function was evaluated using the six-point modification of diet in renal disease formula (estimated glomerular filtration rate [eGFR]). Forty-two patients on SRL and 40 on CNI had at least three months of follow-up and are included in the eGFR evaluation. At all time points after conversion, the EC group demonstrated a significantly higher mean eGFR than those in the LC group. A significant improvement in eGFR was seen within the EC group when comparing eGFR at time of conversion to eGFR at three, six, nine, and 12 months after conversion and last follow-up. The only improvement in the LC group was from conversion to the three-month time point. We conclude that EC to SRL results in a profound improvement in eGFR that begins at three months and is sustained beyond one yr.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Rim/fisiologia , Transplante de Fígado/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Sirolimo/uso terapêutico , Inibidores de Calcineurina , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
Clin Transplant ; 22(3): 281-91, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18482049

RESUMO

BACKGROUND: Promising data regarding the safety and efficacy of gastric bypass surgery (GBS) as an option to address obesity in the transplant population are emerging. The data lack on how GBS may alter the pharmacokinetics (PK) of modern immunosuppression. The objective of this study was to describe the alterations in the PK of modern immunosuppressants and the GBS population. METHODS: Data are presented on six subjects who participated in this trial--four were on dialysis and two were renal transplant recipients. Dialysis-dependent bypass subjects received a single dose of 6 mg of sirolimus, two 4-mg doses of tacrolimus and two 1000-mg doses of mycophenolate mofetil (MMF) over the 24-h study period. Transplant recipients continued their current regimen. Maximum plasma concentration (C(max)), time to reach the maximum plasma concentration (T(max)) and the area under the plasma concentration vs. time curve (AUC(0-12) and AUC(0-infinity) where appropriate) were calculated for tacrolimus, sirolimus, mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG). RESULTS: Significant inter-patient variability in the C(max), T(max) and AUC of tacrolimus, sirolimus MPA and MPAG was observed. A notable difference in the AUC:dose ratio for tacrolimus was seen when comparing data with published data in the non-bypass population. Similar differences in PK were seen with sirolimus, MPA and MPAG. CONCLUSIONS: When comparing the PK of sirolimus, tacrolimus, MPA and MPAG to published PK data in the non-bypass population, significant differences are observed. It is likely that transplant recipients with GBS would need higher doses of tacrolimus, sirolimus and MMF to provide similar exposure to a non-bypass patient.


Assuntos
Derivação Gástrica , Imunossupressores/farmacocinética , Falência Renal Crônica/metabolismo , Transplante de Rim , Ácido Micofenólico/farmacocinética , Sirolimo/farmacocinética , Tacrolimo/farmacocinética , Adulto , Glucuronídeos/farmacocinética , Humanos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Projetos Piloto , Diálise Renal , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem
6.
Transplantation ; 80(1): 26-33, 2005 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16003229

RESUMO

BACKGROUND: Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. METHODS: Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. RESULTS: One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). CONCLUSIONS: Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Peso Corporal/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , Aumento de Peso/efeitos dos fármacos , Índice de Massa Corporal , Esquema de Medicação , Quimioterapia Combinada , Seguimentos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/microbiologia , Teste de Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Transplante de Rim/imunologia , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Sirolimo/administração & dosagem , Sirolimo/uso terapêutico , Fatores de Tempo
7.
Am J Health Syst Pharm ; 72(10): 781-93, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25941253

RESUMO

PURPOSE: Pharmacotherapy concerns and other factors with a bearing on patient selection for kidney transplantation are discussed. SUMMARY: The process of selecting appropriate candidates for kidney transplantation involves multidisciplinary assessment to evaluate a patient's mental, social, physical, financial, and medical readiness for successful surgery and good posttransplantation outcomes. Transplantation pharmacists can play important roles in the recognition and stratification of pharmacologic and nonpharmacologic risks in prospective kidney transplant recipients and the identification of issues that require a mitigation strategy. Key pharmacotherapy-related issues and considerations during the risk assessment process include (1) anticoagulation concerns, (2) cytochrome P-450 isoenzyme-mediated drug interactions, (3) mental health-related medication use, (4) chronic pain-related medication use, (5) medication allergies, (6) use of hormonal contraception and replacement therapy, (7) prior or current use of immunosuppressants, (8) issues with drug absorption, (9) alcohol use, (10) tobacco use, (11) active use of illicit substances, and (12) use of herbal supplements. Important areas of nonpharmacologic risk include vaccine delivery, infection prophylaxis and treatment, and socially related factors such as nonadherent behavior, communication barriers, and financial, insurance, or transportation challenges that can compromise posttransplantation outcomes. CONCLUSION: Consensus opinions of practitioners in transplantation pharmacy regarding the pharmacologic and nonpharmacologic factors that should be considered in assessing candidates for kidney transplantation are presented.


Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Conduta do Tratamento Medicamentoso , Humanos , Medição de Risco
8.
AIDS Patient Care STDS ; 26(10): 568-81, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23025916

RESUMO

Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.


Assuntos
Inibidores da Fusão de HIV/farmacologia , Inibidores de Integrase de HIV/farmacologia , Inibidores da Protease de HIV/farmacologia , Soropositividade para HIV/tratamento farmacológico , Imunossupressores/farmacologia , Transplante de Rim , Transplante de Fígado , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Inibidores da Fusão de HIV/farmacocinética , Inibidores de Integrase de HIV/farmacocinética , Inibidores da Protease de HIV/farmacocinética , Soropositividade para HIV/complicações , Soropositividade para HIV/imunologia , HIV-1 , Humanos , Imunossupressores/farmacocinética , Transplante de Rim/imunologia , Transplante de Fígado/imunologia , Masculino
9.
Transplantation ; 92(6): 653-7, 2011 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-21788920

RESUMO

BACKGROUND: The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. METHODS: Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. RESULTS: Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. CONCLUSIONS: These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.


Assuntos
Terapia de Imunossupressão/economia , Imunossupressores/economia , Imunossupressores/uso terapêutico , Transplante de Órgãos/métodos , Tacrolimo/economia , Tacrolimo/uso terapêutico , Área Sob a Curva , Custos de Medicamentos , Substituição de Medicamentos , Medicamentos Genéricos , Feminino , Humanos , Terapia de Imunossupressão/métodos , Transplante de Rim/métodos , Transplante de Fígado/métodos , Masculino , Estudos Prospectivos , Risco , Resultado do Tratamento
10.
Am J Transplant ; 5(2): 356-65, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15643996

RESUMO

African-Americans (AAs) have historically been considered high-risk renal transplant recipients due to increased rejection rates and reduced long-term graft survival. As a result, AAs are often excluded from corticosteroid withdrawal (CSWD) protocols. Modern immunosuppression has reduced rejections and improved graft survival in AAs and may allow successful CSWD. Outcomes in 56 AAs were compared to 56 non-AAs. All patients were enrolled in one of four early CSWD protocols. Results are reported as AA versus non-AA. Acute rejection at 1-year was 23% and 18%; (p = NS); creatinine clearance at 1-year was 75 versus 80 mL/min (p = NS); patient and graft survival was 96% versus 98% and 91% versus 91%; (p = NS). AAs benefit from early CSWD with significantly improved blood pressure, LDL < 130 mg/dL and HDL > 45 mg/dL at 1-year, post-transplant diabetes of 8.7%, and mean weight change at 1-year of 4.8 +/- 7.2 kg. In conclusion, early CSWD in AAs is associated with acceptable rejection rates, excellent patient and graft survival, and improved cardiovascular risk, indicating that the risks and benefits of early CSWD are similar between AAs and non-AAs. Additional follow-up is needed to determine long-term renal function, graft survival, and cardiovascular risk in AAs with early CSWD.


Assuntos
Corticosteroides/farmacologia , Transplante de Rim , Negro ou Afro-Americano , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Terapia de Imunossupressão , Sobrevida , Fatores de Tempo
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