RESUMEN
Homozygosity for apolipoprotein-L1 (APOL1) risk variants has emerged as an important predictor of renal disease in individuals of African descent over the past several years. Additionally, these risk variants may be important predictors of renal allograft failure when present in a living or deceased donor. Currently, there is no universal recommendation for screening of potential donors. We present a case of end-stage renal disease with focal segmental glomerulosclerosis in a living donor 7 years following donor nephrectomy. Genetic assessment revealed homozygosity for the G1 high-risk APOL1 variant.
Asunto(s)
Apolipoproteína L1/genética , Variación Genética , Fallo Renal Crónico/etiología , Trasplante de Riñón/efectos adversos , Donadores Vivos , Adulto , Negro o Afroamericano , Biomarcadores , Femenino , Genotipo , Tasa de Filtración Glomerular , Homocigoto , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Pruebas de Función Renal , Pronóstico , Factores de Riesgo , Recolección de Tejidos y ÓrganosRESUMEN
Traditionally, chronic calcineurin inhibitor (CNI) nephrotoxicity has been considered to be one of the main nonimmune mechanisms causing chronic renal allograft dysfunction. CNI minimization and withdrawal strategies have yielded inconsistent results. Few studies address the feasibility of CNI elimination in a prednisone-free regimen. We report a prospective, randomized trial in 200 patients evaluating the impact on renal function and incidence of acute rejection after conversion from tacrolimus (Tac) to sirolimus (SRL). Patients with recent (<3 months) acute rejection episodes or with >0.5 g/day of proteinuria were excluded. All were induced with alemtuzumab, underwent rapid steroid elimination and were maintained on mycophenolate mofetil and Tac. At 12 months posttransplant, patients were randomized 2:1 to SRL (n = 123) or maintained on Tac (n = 64). Mean follow-up was 41.1 ± 15.8 months in the SRL group and 40.7 ± 14.4 months in the Tac group. Biopsy-proven acute rejection at 24 months postrandomization was similar between the groups. Patient survival, graft survival and estimated GFR were also not statistically different. Our study demonstrates that in a prednisone-free immunosuppressive regimen, conversion from Tac to SRL at 12 months posttransplantation is not associated with increased rates of acute rejection and graft loss. However, despite CNI elimination, renal allograft function is equally maintained in both groups.
Asunto(s)
Inhibidores de la Calcineurina , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Tacrolimus/uso terapéutico , Adulto , Aloinjertos , Antiinflamatorios/administración & dosificación , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prednisona/administración & dosificación , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
Reactivation of latent CMV in transplant recipients remains a significant infectious complication of transplantation. Investigation of the cellular and molecular mechanisms by which reactivation occurs has been hampered by the lack of appropriate animal models. Here, we show that transplantation of kidneys latently infected with murine cytomegalovirus (MCMV) into NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /Szj mice results in reactivation of latent virus in the kidney, resulting in a disseminated primary infection of the recipient. This model will be useful in elucidating mechanisms of MCMV reactivation, including the roles of injury and of spontaneous reactivation, and in testing new therapies for treatment and prevention of CMV reactivation and disease.
Asunto(s)
Infecciones por Citomegalovirus/transmisión , Modelos Animales de Enfermedad , Trasplante de Riñón/efectos adversos , Muromegalovirus/fisiología , Activación Viral , Latencia del Virus , Animales , Infecciones por Citomegalovirus/virología , ADN Viral/genética , Subunidad gamma Común de Receptores de Interleucina/fisiología , Riñón/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Reacción en Cadena de la Polimerasa , Trasplante HomólogoRESUMEN
Generally chronic steroid therapy is standard care for African American (AA) kidney recipients because of their higher incidence of rejections and lower long-term graft survival. This prospective study evaluated the long-term safety and efficacy of early steroid withdrawal (ESW) in AA recipients. A total of 206 recipients were studied; 103 AA and 103 non-AA recipients monitored by serial surveillance biopsies from 1 to 60 months posttransplantation to evaluate subclinical acute rejections (SCAR) and chronic allograft injury (CAI). Biopsy-proven clinical acute rejections (BPAR) and SCAR were treated. Primary end point was BPAR and secondary end points were 5-year SCAR, CAI and survival. Incidences of BPAR was 16% versus 14% (p = 1.0), prevalence of CAI due to hypertension was 48% versus 30% (p = 0.05) and interstitial fibrosis/tubular atrophy was 47% versus 32% (p = 0.05) and the mean serum creatinine levels were 2.1 versus 1.8 mg/dL (p = 0.05) at 5-years in AA versus non-AA recipients. The incidence of SCAR was 23% versus 11% at 1 month (p = 0.04), 12% versus 3% at 3 years (p = 0.04) and 10% versus 1% at 5 years (p = 0.04) in AA and non-AA recipients, respectively. Five-year patient survivals were 81% and 88% (p = 0.09) and graft survivals were 71% and 73%(p = 0.19) in AA and non-AA groups, respectively. After early steroid withdrawal AA kidney recipients have significantly lower renal function and higher SCAR and CAI but 5-year graft survival are comparable to non-AA recipients.
Asunto(s)
Negro o Afroamericano , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Terapia de Inmunosupresión , Trasplante de Riñón , Esteroides/administración & dosificación , Adulto , Biopsia , Femenino , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Incidencia , Donadores Vivos , Masculino , Estudios Prospectivos , Proteinuria/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Intestinal transplantation is used in patients with short-bowel syndrome after repeated resections for Crohn's disease. We report the apparent clinical recurrence of Crohn's disease in a transplanted intestine. METHODS AND FINDINGS: The patient, a 33-year-old Hispanic woman, underwent small-bowel transplantation in December, 1994. Immunosuppression with tacrolimus, methylprednisolone, bone-marrow infusions, and OKT3 was given. In July, 1995, the patient had recurrent abdominal symptoms. The histological diagnosis of Crohn's disease was established by the independent interpretations of four experienced gastrointestinal histopathologists. INTERPRETATION: The prompt appearance of this autoimmune disorder (within 6 months of transplantation), despite massive immunosuppression may provide important insights into the nature of Crohn's disease and of the recurrence of autoimmune disease during immunosuppression.
Asunto(s)
Enfermedad de Crohn/patología , Enfermedad de Crohn/cirugía , Intestino Delgado/patología , Intestino Delgado/trasplante , Adulto , Colon/patología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Yeyunostomía , Recurrencia , Síndrome del Intestino Corto/etiología , Síndrome del Intestino Corto/cirugíaRESUMEN
This paper reports a case of migrating intravascular bullet embolus that initially produced no symptoms but resulted in an above-knee amputation 14 months after its entry into a peripheral artery. The missile entered through a penetrating gunshot wound to the abdominal aorta and later became lodged in the left popliteal artery. However, the bullet fragment migrated further into the posterior tibial artery with consequent vascular insufficiency requiring a supracondylar amputation of the left lower extremity 14 months later. Emphasis is placed on the need for a high index of suspicion for bullet embolism, aggressive search for any bullets unaccounted for, and early surgical removal of all confirmed arterial emboli.