RESUMO
Interactions between azole antifungal agents and immunosuppressants that are metabolized by cytochrome P450 3A4 (chiefly calcineurin inhibitors) are well documented. Interactions between itraconazole and sirolimus are known to occur in patients after solid organ transplantation, but interactions in hematopoietic stem cell transplant (HSCT) recipients have yet to be reported in the literature. We describe an allogeneic HSCT recipient who experienced supratherapeutic trough levels of sirolimus as a result of its coadministration with itraconazole. This patient was a 20-year-old African-American man who underwent HSCT for treatment of myelodysplastic syndrome with severe aplastic anemia. After several regimen changes, the patient received oral itraconazole 200 mg every 12 hours and sirolimus at a dosage of 7 mg/day on days 76-80 and 5 mg/day on days 81 and 82. His sirolimus whole blood trough levels were 17.5 and 35.6 ng/ml on days 80 and 82, respectively (therapeutic range 5-15 ng/ml). An interaction between itraconazole and sirolimus was suspected, and sirolimus was withheld on days 83-90. On day 90, the patient's sirolimus trough level had normalized to 4.4 ng/ml. Sirolimus was resumed at 1-2 mg/day, with adjustments as needed to maintain trough levels of 10-15 ng/ml. Both the itraconazole and sirolimus were eventually were discontinued. The patient died, however, from a disseminated adenovirus infection leading to end-organ failure. Sirolimus is extremely sensitive to the inhibitory potential of azole antifungals. We propose that itraconazole also has a potent effect on sirolimus metabolism. Preemptive sirolimus dosage reduction and close monitoring of its whole blood trough levels are required whenever this combination is considered to avoid immunosuppressant toxicity in already critically ill patients.
Assuntos
Antifúngicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/efeitos adversos , Itraconazol/efeitos adversos , Sirolimo/efeitos adversos , Infecções por Adenoviridae/complicações , Adulto , Anemia Aplástica/terapia , Transplante de Medula Óssea/imunologia , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Evolução Fatal , Humanos , Imunossupressores/farmacocinética , Masculino , Síndromes Mielodisplásicas/terapia , Sirolimo/farmacocinéticaRESUMO
BACKGROUND: It has been suggested that the use of antilymphocyte induction therapy in African-American (AA) renal transplant recipients reduces the risk of acute rejection (AR) and improves graft survival. It is not clear whether the efficacy of basiliximab (BSX) is different from that of Thymoglobulin (ATG) in this regard. METHODS: We retrospectively assessed the effect of induction therapy with BSX versus ATG in 88 AA renal allograft recipients receiving transplants at our center between July 2001 and June 2003 and followed for 19+/-7 months. All patients were maintained on mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus. Study endpoints included patient and graft survival, graft function, and incidence of AR and cytomegalovirus infection. Regression models were used to evaluate the independent effect of each induction agent on these endpoints. RESULTS: Thirty-six patients received ATG, and 52 received BSX. The groups were comparable with regard to donor race and age, and recipient sex, body mass index, human leukocyte antigen (HLA) matching, and hepatitis C virus serostatus. The ATG group was younger, more likely to receive retransplant, had longer duration of end-stage renal disease and higher panel reactive antibody, and was less likely to receive live-donor organs. However, after adjusting for all these variables, graft outcomes, as well as renal function, were comparable between the two induction groups. We found that the degree of HLA mismatch, delayed graft function, and AR were the only significant predictors of graft loss. CONCLUSION: The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.
Assuntos
Anticorpos Monoclonais/imunologia , Soro Antilinfocitário/imunologia , Negro ou Afro-Americano , Sobrevivência de Enxerto/imunologia , Imunoterapia , Transplante de Rim/imunologia , Proteínas Recombinantes de Fusão/imunologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab , Creatina/sangue , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Transplante , Transplante Homólogo/imunologiaRESUMO
BACKGROUND: There is a paucity of data regarding the use of steroid-avoidance immunosuppression (SAI) in African American (AA) renal allograft recipients, traditionally considered a high-risk subgroup of patients with higher reported rates of acute rejection and graft loss. METHODS: We compared the outcomes of 27 AA renal allograft recipients receiving SAI (SA group; mean follow-up period, 12 +/- 3 mo) with those of 20 patients receiving a steroid taper (ST group; 24 +/- 11 mo). In both groups, thymoglobulin was used for induction, and mycophenolate mofetil and tacrolimus were used for maintenance. Four doses of methylprednisolone were given on days 0 to 3. In the SA group no further steroids were given, whereas in the ST group a prednisone taper was continued thereafter. RESULTS: ST patients were more likely to have current panel reactive antibody titers greater than 10%, undergo retransplantation, and receive more doses of thymoglobulin. There were no significant differences between the SA and ST groups with regard to patient survival (96% vs 95%), graft survival (96% vs 90%), acute rejection (11% vs 14%), cytomegalovirus infection (7% vs 10%), posttransplant diabetes mellitus (11% vs 24%), or mean serum creatinine concentration at 6 months (1.6 vs 1.5 mg/dL), respectively, with a trend toward less percent weight gain in SA patients at 6 months (5% vs 11%, P = .06). CONCLUSIONS: SAI can produce excellent short-term results in AA kidney transplant patients when compared with a conventional ST protocol. Our results will need to be verified in larger numbers of patients with longer follow-up evaluation.
Assuntos
Corticosteroides/administração & dosagem , Negro ou Afro-Americano , Transplante de Rim , Doença Aguda , Corticosteroides/uso terapêutico , Adulto , Biópsia , Estudos de Casos e Controles , Esquema de Medicação , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Incidência , Rim/patologia , Transplante de Rim/mortalidade , Leucopenia/epidemiologia , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
A ventricular assist device (VAD) is an implantable mechanical device that is used to partially or completely replace the circulatory function of a failing heart. VADs may serve as a bridge to heart transplantation or as permanent circulatory assistance, also referred to as destination therapy. There is a paucity of information regarding the nutrition complications in VAD patients, and as such, little is presently known of the optimal means of nutrition assessment and management of these complex and often critically ill patients. In this review, a general overview of the VAD, comparisons of nutrition assessment measures, and strategies to meet the nutrition needs of these patients are provided using evidence-based information wherever possible. Because there is a lack of nutrition studies and assessment guidelines specifically for VAD patients, many of the guidelines for care of these patients are currently based on the information available for the care of patients with heart failure. Although the optimal measure to assess nutrition status remains poorly studied, a systematic, thorough nutrition assessment of patients with heart failure and heart transplant candidates prior to VAD placement appears to be important to identify those at nutrition risk and, with appropriate nutrition therapy, decrease their risk for morbidity and mortality. VAD patients with inadequate oral intake may require nutrition support to meet their nutrition needs; however, feeding the hemodynamically compromised patient provides additional challenges.
Assuntos
Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar , Avaliação Nutricional , Apoio Nutricional , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Hemodinâmica , Humanos , Desnutrição/diagnóstico , Desnutrição/prevenção & controleRESUMO
BACKGROUND: The impact of newer immunosuppressive and antimicrobial prophylactic agents on the pattern of infectious complications following kidney transplantation has not been well studied. METHODS: This is an observational study in 127 adult recipients transplanted from 2001 to 2004. Patients received thymoglobulin (ATG) (50%) or basiliximab (50%) for induction and were maintained on mycophenolate mofetil, either tacrolimus (73%) or sirolimus (SRL) (27%), and prednisone (79%). Antimicrobial prophylaxis included perioperative cefazolin, trimethoprim/sulfamethaxazole for six months, valganciclovir for three months and nystatin for two months. Regression models were used to examine the association of various factors with infections. RESULTS: We observed 127 infections in 65 patients, consisting of urinary tract infection (UTI) (47%), viral infections (17%), pneumonia (8%) and surgical wound infections (7%). UTI was the most common infection in all post-transplant periods. Enterococcus spp. (33%) and Escherichia coli (21%) were the most prevalent uropathogens. Of six patients with cytomegalovirus infection, none had tissue-invasive disease. There were no cases of pneumocystis pneumonia or BK nephropathy. Six patients developed fungal infections. Two deaths due to disseminated Rhizopus and Candida albicans accounted for a 1.5% infection-related mortality. Retransplantation and ureteral stents were independently associated with UTI (OR=4.5 and 2.9, p=0.06 and 0.03, respectively), as were ATG and SRL with bacterial infections (OR=3.3 and 2.5, p=0.009 and 0.047, respectively). CONCLUSION: This study suggests that the use of newer immunosuppressive agents in recent years is associated with some changes in the epidemiology of post-transplant infections. Enterococci have become the predominant uropathogen. Invasive fungal infections, although rare, are often fatal.
Assuntos
Infecções/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/imunologia , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Doadores de Tecidos/estatística & dados numéricos , Infecções Urinárias/epidemiologiaRESUMO
The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.
Assuntos
Teste de Histocompatibilidade/métodos , Transplante de Rim/imunologia , Adulto , População Negra , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Falha de Tratamento , Resultado do Tratamento , Estados UnidosRESUMO
There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African-American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 +/- 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R-) received 900 mg (n = 12); moderate risk (D+/R+, D-/R+) received 450 mg (n = 60); and low risk (D-/R-) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R- serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Ganciclovir/uso terapêutico , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Adulto , Negro ou Afro-Americano , Idoso , Anticorpos Monoclonais/uso terapêutico , Antígenos Virais/sangue , Soro Antilinfocitário/uso terapêutico , Antivirais/administração & dosagem , Basiliximab , Citomegalovirus/imunologia , Infecções por Citomegalovirus/diagnóstico , Feminino , Seguimentos , Ganciclovir/administração & dosagem , Humanos , IMP Desidrogenase/antagonistas & inibidores , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Fosfoproteínas/sangue , Prednisona/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Medição de Risco , Testes Sorológicos , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Valganciclovir , Proteínas da Matriz Viral/sangueRESUMO
Sirolimus (SRL) is a macrolide immunosuppressant that has gained widespread use in organ transplantation. Its full spectrum of side-effects is yet to be defined. We describe herein three cases of SRL-induced angioedema (AE) in African-American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow-up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side-effect, especially in AA patients, is warranted.
Assuntos
Angioedema/induzido quimicamente , Imunossupressores/efeitos adversos , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Sirolimo/efeitos adversos , Negro ou Afro-Americano , Quimioterapia Combinada , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Cuidados Pós-Operatórios , Retratamento , Transplante HomólogoRESUMO
West Nile virus (WNV) has emerged as an important cause of several outbreaks of febrile illness and encephalitis in North America over the past few years. The most common manifestation in symptomatic patients is a transient febrile illness. Neuroinvasive disease, that can be fatal, occurs most often in elderly and immunocompromised hosts. The role of this virus as a cause of meninoencephalitis in organ transplant recipients is becoming better recognized. We describe herein the clinical course of two renal allograft recipients who developed WNV encephalitis. One patient developed status epilepticus and eventually died, while the other had a full recovery. In both cases, the diagnosis was confirmed by detection of WNV-specific IgM in CSF or serum, with a delayed antibody response in one patient. This viral infection should be considered in all renal transplant recipients who present with a febrile illness associated with neurological symptoms.