RESUMEN
BACKGROUND: There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. METHODS: This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. RESULTS: A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. CONCLUSION: This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Corazón , Terapia de Inmunosupresión , Inmunosupresores , Humanos , Masculino , Femenino , Estudios Retrospectivos , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Persona de Mediana Edad , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Pronóstico , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Adulto , Complicaciones Posoperatorias , Tasa de Supervivencia , Trasplante de Hígado/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Corazón-Pulmón/mortalidad , Factores de Riesgo , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Manejo de la EnfermedadRESUMEN
Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m2. BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m2 in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m2 or BMI 25 to <30 kg/m2. In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m2 experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m2 or BMI 25 to <30 kg/m2. These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients.
Asunto(s)
Abatacept , Índice de Masa Corporal , Rechazo de Injerto , Supervivencia de Injerto , Inmunosupresores , Trasplante de Riñón , Obesidad , Humanos , Abatacept/uso terapéutico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Trasplante de Riñón/efectos adversos , Obesidad/complicaciones , Inmunosupresores/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Incidencia , Supervivencia de Injerto/efectos de los fármacos , Factores de Riesgo , Estudios de Seguimiento , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Tasa de Filtración Glomerular , Pronóstico , Adulto , Pruebas de Función Renal , Complicaciones PosoperatoriasAsunto(s)
COVID-19 , Trasplante de Órganos , Anticuerpos Neutralizantes , Humanos , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.
Asunto(s)
COVID-19 , Trasplante de Órganos , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios Retrospectivos , Trasplante de Órganos/efectos adversos , Receptores de TrasplantesRESUMEN
Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Lactamas , Leucina , Nitrilos , Prolina , Ritonavir , Receptores de Trasplantes , Adulto , Inhibidores de la Calcineurina/uso terapéutico , Ciclosporina/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Lactamas/uso terapéutico , Leucina/uso terapéutico , Nitrilos/uso terapéutico , Trasplante de Órganos , Prolina/uso terapéutico , Estudios Retrospectivos , Ritonavir/uso terapéutico , Sirolimus/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
The recommended initial weight-based dose of extended-release (XR) tacrolimus (Envarsus XR) in kidney transplant recipients (KTR) is 0.14 mg/kg/day. However, no data exist regarding dosing recommendations for obese patients specifically. The aim of this study was to evaluate weight-based dosing requirements in a cohort of obese KTR who were initiated on de novo tacrolimus XR post-transplantation. The primary outcome was weight-based dosing requirements (mg/kg/day) on post-operative day (POD) 7 and 14. Of the 254 KTR, 81 (31%) were obese. The median therapeutic dose on POD7 was 0.1 versus 0.12 vs. 0.14 mg/kg/day in the BMI > 30 kg/m2 , BMI 25-30 kg/m2 , and BMI < 25 kg/m2 , respectively, (p = .0001). This result was similar on POD14; median therapeutic dose was 0.09 versus 0.11 versus 0.15 mg/kg/day in the BMI > 30 kg/m2 , BMI 25-30 kg/m2 , and BMI < 25 kg/m2 , respectively, (p < .001). Therapeutic dose on POD7 and POD14 based on ideal body was similar in all cohorts (p = .238, p = .923, respectively). This finding was supported by a strong linear relationship between ideal body weight (IBW) and therapeutic dose (r = .929). In both obese and non-obese KTR, IBW had a stronger correlation with the therapeutic dose for tacrolimus XR.
Asunto(s)
Trasplante de Riñón , Tacrolimus , Humanos , Inmunosupresores/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Tacrolimus/uso terapéutico , Receptores de TrasplantesRESUMEN
BACKGROUND: The purpose of this study was to evaluate outcomes of bleeding and thrombosis resulting from the use of direct oral anticoagulants (DOACs) in a large cohort of solid organ transplant (SOT) recipients. METHODS: This was a single center, retrospective cohort study of adult kidney, heart, lung, and liver transplant recipients transplanted between August 2009 and May 2018. Patients were stratified into two groups: those who received apixaban (apixaban group) or those patients receiving either rivaroxaban or dabigatran (non-apixaban group). The primary endpoint was the cumulative incidence of bleeding while receiving DOAC therapy. The secondary endpoints were incidence of major bleeding and thrombosis at any time while receiving DOAC therapy. RESULTS: A total of 106 patients were included; 70 patients received apixaban and 36 patients received non-apixaban anticoagulation. Cumulative incidence of any bleeding was lower in the apixaban group compared to the non-apixaban group at both 90 days (4.9% vs. 16.1%) and 180 days (11.4% vs. 24.9%, P = .034). Cumulative incidence of major bleeding (P = .686) and thrombosis (P = .515) were similar between groups. DOAC dosing congruent with the package insert(s) was associated with a lower risk of thrombosis. CONCLUSION: Apixaban-based anticoagulation was associated with a lower cumulative incidence of any bleeding compared to non-apixaban DOACs.
Asunto(s)
Fibrilación Atrial , Trasplante de Órganos , Accidente Cerebrovascular , Administración Oral , Adulto , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/inducido químicamente , Humanos , Pirazoles , Piridonas , Estudios RetrospectivosRESUMEN
Solid organ transplantation is a life-saving procedure for patients in the end stage of heart, lung, kidney, and liver failure. For patients with more than one failing organ, simultaneous organ transplantation has emerged as a viable treatment option. Immunosuppression strategies and outcomes for simultaneous organ transplant recipients have been reported, but often involve limited populations. Transplanting dual organs poses challenges in terms of balancing immunosuppression with immunologic risk and allograft damage from surgical complications. Furthermore, transplanting certain organs can impose considerations on the management of immunosuppression. For example, liver allografts may confer immunologic privilege and lower rates of rejection of other allografts. This review article evaluates immunosuppression strategies for simultaneous kidney-pancreas, liver-kidney, heart-kidney, heart-liver, heart-lung, lung-liver, and lung-kidney transplants. To date, no comprehensive review exists to address immunosuppressive strategies in simultaneous organ transplant populations. Our review summarizes the available literature and provides evidence-based recommendations regarding immunosuppression strategies in simultaneous organ transplant recipients.
Asunto(s)
Terapia de Inmunosupresión , Inmunosupresores/farmacocinética , Trasplante de Órganos , Corazón , Humanos , Inmunosupresores/sangre , Riñón , Hígado , Pulmón , PáncreasAsunto(s)
COVID-19/epidemiología , Rechazo de Injerto/tratamiento farmacológico , Trasplante de Órganos , SARS-CoV-2 , Tacrolimus/farmacocinética , Receptores de Trasplantes , Adulto , Comorbilidad , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/metabolismo , Humanos , Inmunosupresores/farmacocinética , Masculino , Persona de Mediana Edad , PandemiasRESUMEN
BACKGROUND: Dapone and atovaquone are therapeutic options for PJP prophylaxis in renal transplant recipients. The objective of this study was to evaluate the incidence of anemia in renal transplant recipients receiving these agents. METHODS: This is an IRB-approved, retrospective analysis of adult renal transplant recipients who received either dapsone or atovaquone. The primary endpoint was the change in hemoglobin within 90 days of drug initiation. Other endpoints of interest included incidence and management of anemia at multiple time points post-transplant. Categorical variables were compared with Pearson's chi-squared or Fischer's exact test and continuous data were compared utilizing Wilcoxon rank-sum test. Statistical analyses were performed using Stata 14.2. RESULTS: A total of 478 patients were screened for inclusion; 50 patients were evaluated in both the dapsone and atovaquone groups. In the dapsone and atovaquone groups, the median age was 52 and 50.5 years, 44% and 42% were Caucasian, and median time to treatment initiation was 27 and 39 days post-transplant, respectively. All patients receiving dapsone had normal G6PD function. There was no difference in baseline hemoglobin between groups (9.7 g/dL vs 9.8 g/dL, P = .83). The median nadir hemoglobin values were 8.6 g/dL and 9.6 g/dL in the dapsone and atovaquone groups, respectively (P = .047). The median decrease in hemoglobin from baseline to nadir was 1.3 g/dL in dapsone patients and 0.2 g/dL in atovaquone patients (P = .001). Dapsone was discontinued in 46% of patients, whereas atovaquone was discontinued in 18% (P = .001). CONCLUSION: Among renal transplant recipients with normal G6PD activity, dapsone is associated with greater hemoglobin reductions and rates of drug discontinuation as compared to atovaquone.
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Anemia , Trasplante de Riñón , Humanos , Pneumocystis carinii , Neumonía por Pneumocystis , Estudios Retrospectivos , Combinación Trimetoprim y SulfametoxazolRESUMEN
Direct oral anticoagulants (DOACs) have become an attractive option for the treatment of venous thromboembolism (VTE) in cancer patients. However, their use is currently not recommended as first-line treatment by national guidelines due to limited data in this patient population. The objective of this study was to evaluate the practice and safety patterns of DOACs when used for VTE treatment in the oncology population. This study was a retrospective chart review of adult cancer patients treated at Hackensack University Medical Center from January 2013 to October 2015 who received dabigatran, rivaroxaban, or apixaban for VTE treatment. Of 126 patients screened, 39 patients were included. Thirty-five patients received rivaroxaban and four patients received apixaban. Ten of 39 patients (26%) were not receiving a DOAC dosage consistent with the package insert. No patients experienced clinically significant bleeding, while four patients experienced a minor bleed. Four of 14 thrombocytopenic patients (29%) did not have their DOAC dose held for thrombocytopenia. All patients had their DOACs appropriately held for procedures. Increased education on dosing DOACs according to the package insert is warranted for oncology prescribers. Despite the increased risk for bleeding in cancer patients, no clinically significant bleeding events were identified in our patient cohort. This data suggests that the use of DOACs may be safe to use for VTE treatment in cancer patients and may provide foundation for larger, randomized controlled trials to determine whether DOACs should be used for VTE treatment in cancer patients.