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BACKGROUND AND OBJECTIVES: The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. RESULTS: Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p < 0.001), 3-year (6.0 vs. 4.3%, p < 0.001) and 5-year follow-up (7.7 vs. 6.4%, p = 0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p = 0.0005), 3-year (7.6 vs. 5.5%, p < 0.001) and 5-year follow-up (11.5 vs. 8.8%, p < 0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p = 0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p = 0.53) or 5-year follow-up (7.2 vs. 8.1%, p = 0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p = 0.98) and at 3 years (5.5 vs. 5.4%, p = 0.45), respectively. CONCLUSION: Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.
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Suero Antilinfocítico , Basiliximab , Rechazo de Injerto , Supervivencia de Injerto , Inmunosupresores , Trasplante de Riñón , Humanos , Basiliximab/uso terapéutico , Basiliximab/administración & dosificación , Masculino , Estudios Retrospectivos , Suero Antilinfocítico/uso terapéutico , Suero Antilinfocítico/administración & dosificación , Femenino , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Inmunosupresores/administración & dosificación , Adulto , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Bases de Datos Factuales , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Resultado del Tratamiento , Esteroides/administración & dosificación , Esteroides/uso terapéutico , Aloinjertos , Factores de TiempoRESUMEN
Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
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Carcinoma de Células Escamosas , Trasplante de Riñón , Neoplasias Cutáneas , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Trasplante de Riñón/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
CLINICAL FEATURES: A middle-aged man with history of kidney transplantation was diagnosed with multiple myeloma (MM); he was treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for induction therapy. However, a repeat bone marrow biopsy after treatment revealed 10% clonal plasma cell involvement. Given residual disease, his treatment regimen was changed to daratumumab, bortezomib, and dexamethasone in an attempt to achieve minimal residual disease. THERAPEUTIC CHALLENGE: Daratumumab was recently approved for treatment of relapsed or refractory MM; there are no data regarding the safety and effectiveness in solid organ transplant patients. SOLUTION: Our patient was treated with a daratumumab-based regimen for MM. His renal function was monitored closely along with donor-specific antibody to assess for risk of graft rejection. His renal function remained stable with minimal proteinuria and negative donor-specific antibody during the treatment course.
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Trasplante de Riñón , Mieloma Múltiple , Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
BACKGROUND: BK virus infection can lead to graft dysfunction and loss in kidney transplant recipients. Risk factors for BKV and BKVN have been inadequately studied in children. Here, we evaluate the incidence and risk factors of allograft loss due to BKVN in the pediatric population of the UNOS data set. METHODS: We conducted a retrospective cohort analysis of the UNOS database and identified all pediatric recipients of kidney transplantation between 2000 and 2018. We compared donor and recipient characteristics, including cause of ESRD, among patients who lost their graft due to BKVN or other causes, and those with functioning allograft. Kaplan-Meier curve and Cox regression analysis were performed to evaluate the risk factors. RESULTS: A total of 66 patients (0.47%) suffered graft failure from BKVN. Older age, male gender, HLA mismatch, and rejection at 1 year were significantly associated with BKVN graft failure, compared to recipients with functioning allograft. In comparison with graft loss due to other causes, male gender, higher HLA mismatch, rejection in 1st year and tacrolimus use at discharge were significantly associated with BKVN graft loss. Recipients who received mycophenolate at time of discharge were at reduced risk for BKVN graft failure. Compared to graft failure from other causes, BKVN graft failure had shorter death censored graft survival [P = .001]. ESRD due to urologic causes and Alport syndrome had higher rate of BKVN graft failure. CONCLUSION: Incidence of graft loss from BKVN in the pediatric population was 10.2 per 10 000 patient-years in this study. BKVN is associated with early allograft failure in the pediatric population, compared to other causes of graft loss. Male gender, HLA mismatch, rejection in 1st year, and urological cause of ESRD are risk factors for graft failure from BKVN in children.
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Rechazo de Injerto/epidemiología , Rechazo de Injerto/virología , Trasplante de Riñón , Infecciones por Polyomavirus/complicaciones , Infecciones Tumorales por Virus/complicaciones , Adolescente , Virus BK/patogenicidad , Niño , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Viremia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Doble Ciego , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/complicaciones , Receptores de Trasplantes , Infecciones Tumorales por VirusRESUMEN
The impact of cytomegalovirus (CMV) serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, recipients with first deceased donor kidney transplant (≥18 years, 2010-2015) were stratified into 4 groups in the main cohort: CMV-seronegative donor (D-)/CMV-seronegative recipient (R-), CMV-seropositive donor (D+)/R-, D+/CMV-seropositive recipient (R+), and D-/R+. In a paired kidney cohort, we identified 2899 pairs of D- kidney transplant with discordance of recipient serostatus (D-/R- vs D-/R+) and 4567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R- vs D+/R+). In the main cohort, D+/R- was associated with a higher risk of graft failure (hazard ratio [HR] = 1.17, P = .01), all-cause mortality (HR = 1.18, P < .001), and infection-related mortality (HR = 1.38, P = .03) compared with D-/R-. In the paired kidney analysis, D+/R- was an independent risk factor for all-cause mortality (HR = 1.21, P = .003) and infection-related mortality (HR = 1.47, P = .04) compared with D+/R+. No difference in graft loss between D+/R- and D+/R+. CMV mismatch is still an independent risk factor for graft loss and patient mortality. The negative impact of D+/R- serostatus on mortality persists after fully matching for donor factors.
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Infecciones por Citomegalovirus/virología , Citomegalovirus/inmunología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Fallo Renal Crónico/cirugía , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias , Adulto , Antivirales/uso terapéutico , Estudios de Cohortes , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/transmisión , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Humanos , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
In the past 20 years, there has been an increase in use of steroid-withdrawal regimens in kidney transplantation. However, steroid withdrawal may be associated with an increased risk of recurrent IgA nephropathy (IgAN). Using United Network of (Organ Sharing/Organ Procurement and Transplantation Network) UNOS/OPTN data, we analyzed adult patients with end-stage renal disease (ESRD) due to IgAN who received their first kidney transplant between 2000 and 2014. For the primary outcome, we used a competing risk analysis to compare the cumulative incidence of graft loss due to IgAN recurrence between early steroid-withdrawal (ESW) and steroid continuation groups. The secondary outcomes were patient survival and death-censored graft survival (DCGS). A total of 9690 recipients were included (2831 in ESW group and 6859 in steroid continuation group). In total, 1238 recipients experienced graft loss, of which 191 (15.43%) were due to IgAN recurrence. In multivariable analysis, steroid use was associated with a decreased risk of recurrence (subdistribution hazard ratio 0.666, 95% CI 0.482-0.921; P = 0.014). Patient survival and DCGS were not different between the two groups. In the USA, ESW in transplant for ESRD due to IgAN is associated with a higher risk of graft loss due to disease recurrence. Future prospective studies are warranted to further address which patients with IgAN would benefit from steroid continuation.
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Corticoesteroides/administración & dosificación , Glomerulonefritis por IGA/tratamiento farmacológico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Privación de Tratamiento , Adulto , Análisis de Varianza , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/mortalidad , Glomerulonefritis por IGA/fisiopatología , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/etiología , Fallo Renal Crónico/fisiopatología , Trasplante de Riñón/métodos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
INTRODUCTION: BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV. METHODS: Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines. RESULTS: Thirteen of 15 centers (86.7%) returned the survey. Only two center reported using monitoring parameters that were in line with consensus guidelines for BKPyV screening, while the majority of centers reported less intensive methods and shorter duration. One center reported performing renal biopsies in all patients with plasma viral loads >10 000 copies/mL, while all other centers only perform for-cause biopsies. For presumptive nephropathy, 11 centers recommend a biopsy for confirmation. For management of documented BKPyV-associated nephropathy, 12 centers propose further immunosuppression reduction. Nine centers report CNI dose reduction as their primary treatment. More than half of centers surveyed reported use of leflunomide, cidofovir or intravenous immunoglobulin. CONCLUSIONS: There was a large variance in BKPyV screening and management strategies among centers. Due to these results, all participating centers agreed to implement uniform screening and aim to optimize management protocols.
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Antivirales/uso terapéutico , Virus BK/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Infecciones Tumorales por Virus/diagnóstico , Aloinjertos/inmunología , Aloinjertos/patología , Aloinjertos/virología , Antivirales/normas , Biopsia , Protocolos Clínicos/normas , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Encuestas de Atención de la Salud/estadística & datos numéricos , Personal de Salud/estadística & datos numéricos , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Riñón/inmunología , Riñón/patología , Riñón/virología , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/patología , Infecciones por Polyomavirus/virología , Guías de Práctica Clínica como Asunto , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/virologíaRESUMEN
BACKGROUND: The contribution of multiple retained nonfunctional arteriovenous grafts (AVGs) to the burden of chronic inflammation in chronic hemodialysis patients has not been well studied. Here, we sought to evaluate the association between plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and albumin and the number of retained nonfunctional AVGs. METHODS: This cross-sectional study enrolled 91 prevalent patients undergoing in-center hemodialysis without evidence of infection or inflammation. A baseline blood sample was obtained at study enrollment. A general linear model (GLM) was used to compare levels of biomarkers of systemic inflammation across groups defined by the number of retained, nonfunctional AVGs. RESULTS: A total of 43 patients had one or more retained thrombosed AVG and had significantly greater plasma log-CRP levels compared with patients without a previous AVG (P= 0.036), regardless of the current AV access type. Using a GLM, we found that for every additional retained thrombosed AVG, plasma log-CRP, log-IL-6 and TNF-alpha concentrations increased significantly by 0.30 mg/L (P= 0.011), 0.18 pg/mL (P= 0.046) and 0.72 pg/mL (P= 0.046), respectively, following adjustment. CONCLUSIONS: Hence, the severity of inflammation increases with the number of retained nonfunctional AVG's, suggesting that AVG accumulation may contribute to the cardiovascular morbidity and mortality associated with chronic inflammation in asymptomatic end-stage renal disease (ESRD) patients. Further study is indicated to determine whether patients with one or more thrombosed, retained AVG may benefit from periodic screening with CRP monitoring to identify those patients who may benefit from AVG resection.
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Derivación Arteriovenosa Quirúrgica , Biomarcadores/análisis , Inflamación/diagnóstico , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos , Trombosis/diagnóstico , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Inflamación/sangre , Inflamación/etiología , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Albúmina Sérica/análisis , Trombosis/sangre , Trombosis/etiología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients. METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and ≥15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type. RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04). CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor.
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Negro o Afroamericano , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etnología , Metaloproteinasa 9 de la Matriz/sangre , Vitamina D/análogos & derivados , Adulto , Anciano , Biomarcadores/sangre , Calcio/sangre , Estudios Transversales , Femenino , Humanos , Inflamación/epidemiología , Interleucina-10/sangre , Fallo Renal Crónico/terapia , Modelos Lineales , Masculino , Persona de Mediana Edad , Fósforo/sangre , Diálisis Renal , Factores de Riesgo , Estados Unidos , Enfermedades Vasculares/epidemiología , Vitamina D/sangreRESUMEN
INTRODUCTION: Kidney dysfunction is not uncommon in patients with advanced heart failure. Simultaneous kidney and heart transplants (SKHTs) have gained acceptance as a treatment for patients with end-stage heart failure and severe kidney dysfunction. United States saw a rise of 650% in SKHT from 2000 to 2019. Despite increasing number of SKHT, the selection criteria remain poorly defined and vary across transplant centers. METHODS: We evaluated patient and cardiac allograft survival for SKHT and heart transplant alone (HTA) using the United Network for Organ Sharing (UNOS) database. We then performed a subgroup analysis in recipients with post-transplant acute kidney injury requiring renal replacement therapy (RRT) and compared outcomes between SKHT and HTA recipients. RESULTS: Although patient survival was comparable between SKHT and HTA groups (12.4 vs. 11.3 years), patients dependent on dialysis pretransplant derived greater survival advantage from SKHT as compared with HTA (12.4 vs. 9.9 years). Cardiac graft survival was better in SKHT (12.5 vs. 11.2 years). Among patients who developed acute kidney injury requiring RRT postoperatively, SKHT recipients had a significantly better survival (11.9 vs. 2.7 years). CONCLUSION: Our data support consideration of SKHT in dialysis-dependent heart transplant candidates and suggest that patients who are at increased risk of requiring RRT after heart transplant may benefit from SKHT.
RESUMEN
Arteriovenous graft in the thigh is used not infrequently for hemodialysis. Outcomes with this lower extremity dialysis access are generally comparable to upper extremity access and superior to long-term catheter use. However, it could have significant implications in a patient getting a kidney transplant. Here we describe a case of thigh arteriovenous graft causing kidney allograft dysfunction in a new transplant recipient, and this resolved with graft ligation.
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Derivación Arteriovenosa Quirúrgica/efectos adversos , Funcionamiento Retardado del Injerto/etiología , Glomerulonefritis por IGA/cirugía , Trasplante de Riñón/efectos adversos , Diálisis Renal , Muslo/irrigación sanguínea , Funcionamiento Retardado del Injerto/diagnóstico por imagen , Funcionamiento Retardado del Injerto/fisiopatología , Funcionamiento Retardado del Injerto/cirugía , Femenino , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/fisiopatología , Humanos , Ligadura , Persona de Mediana Edad , Recuperación de la Función , Resultado del Tratamiento , Presión VenosaRESUMEN
Serum phosphorus levels in the general population have been reported to be associated with cardiovascular morbidity and mortality and increased carotid intima-media thickness. The authors examined gender heterogeneity in the association of phosphorus with all-cause mortality and incident coronary artery disease using data from the Atherosclerosis Risk in Communities Study (1987-2001). Baseline phosphorus levels were higher in women and were associated differently among men and women with traditional atherosclerosis risk factors such as age, low density lipoprotein cholesterol, diabetes mellitus, and hypertension. In a multivariable-adjusted model, men in the highest quintile of serum phosphorus level (>3.8 mg/dL) had an increased mortality rate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88), while women did not (hazard ratio = 1.18, 95% confidence interval: 0.89, 1.57). The multivariable likelihood ratio test of effect modification by gender was significant at alpha = 0.1 (P = 0.085) for all-cause mortality. Although the associations of phosphorus with coronary artery disease also appeared to differ substantially by gender, the multivariable test for effect modification suggested that the difference was consistent with random variation (P = 0.195). These results suggest the need for further investigation into gender differences in the contribution of mineral metabolism to cardiovascular disease in the general population.
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Enfermedad Coronaria/sangre , Enfermedad Coronaria/mortalidad , Fósforo/sangre , Factores de Edad , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , LDL-Colesterol/sangre , Intervalos de Confianza , Enfermedad Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , Análisis Multivariante , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85-4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21-4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77-18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58-34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28-2.30, p < 0.01 and SHR 3.44, 95%CI 1.25-9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14-33.15, p = 0.04; HR 17.97, 95%CI 1.81-178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized.
RESUMEN
We are presenting a case of a middle-aged woman with history of remote kidney transplantation who had multiple admissions for septic shock-like picture, recurrent fever, and hypotension. Her shock manifestation would resolve after stress dose steroid administration and less than 24 hours of vasopressor administration. Initially, extensive workup was performed without revealing etiology. Eventually, a bone marrow biopsy was carried out leading to the diagnosis of hemophagocytic lymphohistiocytosis, most likely related to recent cytomegalovirus infection.
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BACKGROUND: Chronic kidney disease (CKD) is a predictor of morbidity and mortality in patients undergoing percutaneous coronary interventions (PCIs), and African American (AA) patients have been reported to have worse outcomes after PCI. METHODS: We assessed whether CKD affects the rate of death and major adverse cardiovascular events (MACE = myocardial infarction, revascularization, and death) differently in AA and white (CC) patients 1 year after PCI. Accordingly, we reviewed the database of all patients referred for PCI in the Emory Healthcare System between January 2001 and December 2004. RESULTS: We identified 800 CC and 116 AA patients with CKD among 4,372 patients referred for PCI. Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) <60 mL/(min 1.73 m(2)) calculated by means of the Cockcroft-Gault equation. The AA patients with CKD were younger and had a larger number of comorbidities than the CC subjects. However, neither mortality nor MACE differed between races (14.7% vs 13.1%, P = .65 and 31.9% vs 31.3%, P = .89, respectively). In multivariable models, eGFR and emergency PCI were the best predictors of any adverse event, whereas prior PCI or coronary artery bypass surgery was a predictor of MACE alone. A test for interaction failed to show a significant effect of race and CKD on outcome. CONCLUSIONS: In a tertiary referral center, AA and CC patients with CKD had a similar mortality rate and MACE at 1 year after PCI. Race was not a determinant of outcome, whereas CKD was.
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Angioplastia Coronaria con Balón , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/etnología , Negro o Afroamericano , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Población BlancaRESUMEN
BACKGROUND AND OBJECTIVES: Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. RESULTS: A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P<0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P=0.18) (P value for interaction <0.01). When taking cold ischemic time into account, HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P=0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P=0.49) (P value for interaction <0.01). Recipients with one or two HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P<0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P=0.02) in living donor kidney transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. CONCLUSIONS: HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants.
Asunto(s)
Antígenos HLA-DQ/inmunología , Prueba de Histocompatibilidad , Trasplante de Riñón , Enfermedad Aguda , Adulto , Isquemia Fría , Femenino , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Antígenos HLA-DR/inmunología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BK polyomavirus (BKPyV) reactivation in kidney transplant recipients can lead to allograft damage and loss. The elements of the adaptive immune system that are permissive of reactivation and responsible for viral control remain incompletely described. We performed a prospective study evaluating BKPyV-specific T-cell response, humoral response and overall T-cell phenotype beginning pre-transplant through one year post-transplant in 28 patients at two centers. We performed an exploratory analysis of risk factors for the development of viremia and viruria as well as compared the immune response to BKPyV in these groups and those who remained BK negative. 6 patients developed viruria and 3 developed viremia. BKPyV-specific CD8+ T-cells increased post-transplant in viremic and viruric but not BK negative patients. BKPyV-specific CD4+ T-cells increased in viremic, but not viruric or BK negative patients. Anti-BKPyV IgG antibodies increased in viruric and viremic patients but remained unchanged in BK negative patients. Viremic patients had a greater proportion of CD8+ effector cells pre-transplant and at 12 months post-transplant. Viremic patients had fewer CD4+ effector memory cells at 3 months post-transplant. Exploratory analysis demonstrated lower CD4 and higher total CD8 proportions, higher anti-BKPyV antibody titers and the cause of renal failure were associated BKPyV reactivation. In conclusion, low CD4, high CD8 and increased effector CD8 cells were found pre-transplant in patients who became viremic, a phenotype associated with immune senescence. This pre-transplant T-cell senescence phenotype could potentially be used to identify patients at increased risk of BKPyV reactivation.