RESUMEN
This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.
Asunto(s)
COVID-19 , Trasplante de Riñón , Prueba de COVID-19 , Humanos , Internet , Trasplante de Riñón/efectos adversos , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
The aim of the study is to provide a comprehensive overview of identical twin kidney transplantation in the modern era. We provide epidemiologic trends in the US twin population from 1959 to 2000, current methods to identify zygosity, outcomes for identical twin transplants, and a comprehensive management strategy for identical twin kidney transplantation. By 2019, we project that 433 010 dizygotic and monozygotic twins will be alive and at risk for developing ESRF. Monozygosity between a donor-recipient pair can be confirmed by concordance in sex, blood type, and HLA antigen match with precision testing using 13/17 Short Tandem Repeat sequencing to a likelihood of nearly 100%. Among identical twin transplants from 2001 to 2017, excellent patient and kidney graft survival rates were noted. Approximately 50% of kidney transplant recipients of identical twins transplant did not receive maintenance immunosuppression, and no differences in graft survival were noted among patients with and without immunosuppression at 6 and 12 months (P = .8 and .7). Patients with glomerulonephritis as the cause of ESRF had lower graft survival (P = .06) suggesting that recurrent glomerulonephritis as a likely cause of graft loss among these recipients.
Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Donadores Vivos , Gemelos MonocigóticosRESUMEN
We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.
Asunto(s)
Biomarcadores/análisis , Etnicidad/genética , Rechazo de Injerto/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Leucocitos Mononucleares/metabolismo , Transcriptoma , Adolescente , Adulto , Anciano , Biopsia , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Rechazo de Injerto/sangre , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long-term follow-up. Our retrospective single-center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow-up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty-four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty-seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.
Asunto(s)
Inmunosupresores/administración & dosificación , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Tuberculosis/complicaciones , Tuberculosis/mortalidad , Abatacept/administración & dosificación , Adulto , Azatioprina/administración & dosificación , Inhibidores de la Calcineurina/administración & dosificación , Infecciones por Citomegalovirus/complicaciones , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Estudios Retrospectivos , Riesgo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
As the number of kidney transplants continues to rise, so does the number and complexities of surgical-related complications, which may be associated with increased morbidity and potentially graft loss. Ureteral stenosis, the most prevalent urological complication, may require diverse techniques for surgical correction depending on several recipient and graft abnormalities. Here we report the surgical and clinical outcomes of a 62-year-old man with a posttransplant pyeloureterostomy stricture successfully treated with ureterocalicostomy after a lower pole nephrectomy. Although the resection of renal parenchyma may prevent a stenosis recurrence, surgeons can be reluctant to use this strategy due to the possible negative impact on renal function. We highlight some key steps of the surgical technique to prevent unnecessary allograft lesion and present short-term outcomes, suggesting that this rarely described procedure is a safe and effective alternative treatment for kidney transplant recipients with pyeloureterostomy stenosis.
Asunto(s)
Trasplante de Riñón/efectos adversos , Nefrectomía/métodos , Complicaciones Posoperatorias/prevención & control , Enfermedades Ureterales/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Pronóstico , Enfermedades Ureterales/etiología , Enfermedades Ureterales/patologíaRESUMEN
Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.
Asunto(s)
Antirretrovirales/farmacología , Rechazo de Injerto/mortalidad , Infecciones por VIH/complicaciones , Trasplante de Riñón/métodos , Complicaciones Posoperatorias/mortalidad , Inhibidores de Proteasas/farmacología , Receptores de Trasplantes , Adulto , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
This study describes patient social networks within a new hemodialysis clinic and models the association between social network participation and kidney transplantation. Survey and observational data collected between August 2012 and February 2015 were used to observe the formation of a social network of 46 hemodialysis patients in a newly opened clinic. Thirty-two (70%) patients formed a social network, discussing health (59%) and transplantation (44%) with other patients. While transplant-eligible women participated in the network less often than men (56% vs. 90%, p = 0.02), women who participated discussed their health more often than men (90% vs. 45.5%, p = 0.02). Patients in the social network completed a median of two steps toward transplantation compared with a median of 0 for socially isolated patients (p = 0.003). Patients also completed more steps if network members were closely connected (ß = 2.23, 95% confidence interval [CI] 0.16-4.29, p = 0.03) and if network members themselves completed more steps (ß = 2.84, 95% CI 0.11-5.57, p = 0.04). The hemodialysis clinic patient social network had a net positive effect on completion of transplant steps, and patients who interacted with each other completed a similar number of steps.
Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón , Diálisis Renal , Red Social , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores Sexuales , Apoyo Social , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Ligando de CD40 , Trasplante de Riñón , Animales , Rechazo de Injerto , Supervivencia de Injerto , PrimatesAsunto(s)
Trasplante de Riñón , Teratología , Femenino , Humanos , Inmunosupresores , Ácido Micofenólico , Embarazo , Resultado del Embarazo , Sistema de RegistrosRESUMEN
Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 106 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen.
Asunto(s)
Células Dendríticas/inmunología , Supervivencia de Injerto/inmunología , Isoantígenos/inmunología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Linfocitos T/inmunología , Donantes de Tejidos , Animales , Leucocitos Mononucleares , Macaca mulatta , Masculino , Tolerancia al Trasplante , Trasplante HomólogoRESUMEN
In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.
Asunto(s)
Anemia de Células Falciformes , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Adulto , Cadáver , Femenino , Humanos , Persona de Mediana Edad , Nefrectomía , PronósticoRESUMEN
Recommendations from the 2014 Consensus Conference on Best Practices in Living Kidney Donation reflect increasing attention to overcoming barriers to donation as a means of expanding access to living donor kidney transplantation. "High priority" initiatives include empowering transplant candidates and their loved ones in their search for a living kidney donor. Transplant programs are assuming an unprecedented role as facilitators of patients' solicitation for donors, and nonprofits are promoting living kidney donation (LKD) in the community. New strategies to promote LKD incorporate "nonargumentative" forms of influence (i.e. approaches to shaping behavior that do not attempt to persuade through reason) such as appeals to emotion, messenger effects and social norms. These approaches have raised ethical concerns in other settings but have received little attention in the transplantation literature despite their increasing relevance. Previous work on using nonargumentative influence to shape patient behavior has highlighted implications for (1) the relationship between influencer and influenced and (2) patient autonomy. We argue that using nonargumentative influence to promote LKD is a promising strategy that can be compatible with ethical standards. We also outline potential concerns and solutions to be implemented in practice.
Asunto(s)
Trasplante de Riñón/ética , Donadores Vivos , Educación del Paciente como Asunto , Guías de Práctica Clínica como Asunto/normas , Recolección de Tejidos y Órganos/ética , Consenso , Humanos , NefrectomíaRESUMEN
This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus-reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V-family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J-gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity.
Asunto(s)
Virus BK/inmunología , Rechazo de Injerto/inmunología , Enfermedades Renales/inmunología , Trasplante de Riñón , Infecciones por Polyomavirus/inmunología , Linfocitos T/inmunología , Infecciones Tumorales por Virus/inmunología , Adulto , Anciano , Especificidad de Anticuerpos , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Enfermedades Renales/genética , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/virología , Receptores de Antígenos de Linfocitos T/genética , Infecciones Tumorales por Virus/virología , Adulto JovenRESUMEN
Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior to kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting of a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney and kidney-pancreas recipients with a negative pretransplant FCXM from September 2007 to August 2012 without desensitization therapy were analyzed with a median follow-up of 4.2 years. All patients underwent cell-based FCXM and SAB analysis on current and historic sera prior to transplantation. One hundred and sixty-two patients (24.5%) had DSA detected prior to transplant. One-year acute rejection rates were similar in DSA-positive versus DSA-negative patients (15.4% vs. 11.4%, respectively; p = 0.18) and were higher in those with DSA mean fluorescence intensity (MFI) greater than or equal to 3000 in multivariable analysis (p = 0.046). The estimated glomerular filtration rate (eGFR) at 3 and 4 years was lower in the DSA(+) versus the DSA(-) group (p = 0.050 at 3 years) without an impact on 5-year death-censored graft survival (89.0% vs. 90.6%, respectively; p = 0.53). Timing (current or historic) of DSA detection did not alter these findings. In conclusion, pretransplant DSA in the setting of a negative FCXM confers minimal immunologic risk in the intermediate term, does not necessitate desensitization therapy and should not represent a barrier to renal transplant.
Asunto(s)
Citometría de Flujo/métodos , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad/métodos , Isoanticuerpos/inmunología , Trasplante de Riñón , Donantes de Tejidos , Desensibilización Inmunológica , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Antígenos HLA/inmunología , Humanos , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Receptores de TrasplantesAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Inmunosupresores/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Ciclosporina/uso terapéutico , Rechazo de Injerto/inducido químicamente , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/patología , Humanos , Trasplante de Riñón , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Nivolumab , Prednisona/uso terapéuticoRESUMEN
Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high-strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes.
Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Humanos , Pruebas de Función Renal , Pronóstico , Tasa de Supervivencia , Privación de TratamientoRESUMEN
Renal ischemia-reperfusion injury (IRI) is a common cause of renal dysfunction and renal failure. Histone/protein deacetylases (HDACs) regulate gene accessibility and higher order protein structures and may alter cellular responses to a variety of stresses. We investigated whether use of pan- and class-specific HDAC inhibitors (HDACi) could improve IRI tolerance in the kidney. Using a model of unilateral renal IRI, we investigated early renal function after IRI, and calculated fibrosis after IRI using an automated scoring system. We found that pan-HDAC inhibition using trichostatin (TSA) yielded significant renal functional benefit at 24-96 hours (p < 0.001). Treated mice developed significantly less fibrosis at 30 days (p < 0.0004). Class I HDAC inhibition with MS-275 yielded similar effects. Protection from fibrosis formation was also noted in a cold ischemia transplant model (p < 0.008) with a trend toward improved cold ischemic survival in TSA-treated mice. These effects were not accompanied by induction of typical ischemic tolerance pathways or by priming of heat shock protein expression. In fact, heat shock protein 70 deletion or overexpression did not alter renal ischemia tolerance. Micro-RNA 21, known to be enhanced in vitro in renal tubular cells that survive stress, was enhanced by treatment with HDACi, pointing to possible mechanism.
Asunto(s)
Fibrosis/prevención & control , Histonas/metabolismo , Isquemia/prevención & control , Riñón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Femenino , Inhibidores de Histona Desacetilasas/farmacología , Ratones , Ratones Endogámicos C57BLRESUMEN
Solid organ transplantation has increased in frequency in the United States, having evolved from an area of experimentation into accepted therapy for end-organ failure. As organ transplantation has become more common, the average age of transplant recipients has increased, thus increasing the potential for multiple comorbidities including coronary artery disease (CAD). CAD has been shown to be a major cause of morbidity and mortality in kidney, lung and liver transplant recipients. Identification of CAD in solid organ transplant candidates allows for stratification of short- and long-term risk, ensuring proper use of valuable allograft resources while guiding further patient management. Assessment of asymptomatic transplant candidates for CAD is difficult. Many patients undergo stress echocardiography or nuclear imaging, which have demonstrated inconsistent rates of sensitivity and specificity for the detection of CAD in these patient populations. Cardiac computed tomography is a potential tool for detecting CAD in these populations, but has questionable utility at this time. Coronary angiography has an important role in detecting CAD in high-risk transplant candidates, affecting their long-term management and risk.