RESUMEN
BACKGROUND: Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating the genome and proteome. They are detectable in the blood of patients with acute kidney injury. We tested whether lncRNAs are present in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection. METHODS: A global lncRNA expression analysis was performed with RNA from urine of patients with acute T cell-mediated renal allograft rejection and control transplant patients. Deregulated lncRNAs were confirmed in kidney biopsies and urine in a validation cohort of 62 patients with acute rejection, 10 of them after successful antirejection therapy, and 31 control transplant patients. RESULTS: A global screen revealed several lncRNAs to be deregulated in urine of patients with acute rejection. Three intergenic lncRNAs, LNC-MYH13-3:1, RP11-395P13.3-001, and RP11-354P17.15-001, were most strongly altered. These were validated in the whole cohort of patients. RP11-395P13.3-001 and RP11-354P17.15-001 were upregulated in patients with acute rejection compared with controls. Only levels of RP11-354P17.15-001 normalized in patients with acute rejection after successful antirejection therapy. RP11-354P17.15-001 was associated with higher decline in glomerular filtration rate 1 year after transplantation. In vitro, in tubular epithelial cells, all lncRNAs were enriched by interleukin-6 treatment, but only RP11-395P13.3-001 and RP11-354P17.15-001 increased in cell culture supernatant, indicating that these lncRNAs might be secreted under inflammatory conditions. CONCLUSIONS: lncRNAs are strongly altered in urine of patients with acute rejection. Urinary RP11-354P17.15-001 may serve as a novel biomarker of acute kidney rejection, identifying patients with acute rejection and predicting loss of kidney function.
Asunto(s)
Lesión Renal Aguda/cirugía , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/orina , ARN Largo no Codificante/orina , Enfermedad Aguda , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Adolescente , Adulto , Anciano , Biomarcadores/orina , Células Cultivadas , Estudios de Cohortes , Diagnóstico Precoz , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Regulación de la Expresión Génica , Tasa de Filtración Glomerular , Rechazo de Injerto/genética , Rechazo de Injerto/patología , Humanos , Interleucina-6/farmacología , Riñón/metabolismo , Riñón/patología , Riñón/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Pronóstico , ARN Largo no Codificante/metabolismoRESUMEN
OBJECTIVE: To assess the potential benefit of virtual dialogues with experts as a method for educating family members and caregivers of patients with an acquired brain injury (ABI). METHODS: Knowledge of ABI was assessed by questionnaire for eight participants prior to and after interacting with a virtual dialogue method, called Virtual Conversations®. Participants also completed a survey regarding their perceived value of the experience. RESULTS: Significant improvement on the Knowledge Questionnaire was apparent from before to after participation in the virtual dialogue by the Wilcoxon Signed-Rank Test (Z = -1.9734; p < 0.05). Five of eight participants showed large improvement on this test. All reported enjoying and learning from the experience. CONCLUSION: The virtual dialogue method increases knowledge of brain injury for most family caregivers. It is an effective and efficient way for family and friends of patients with ABI to learn about ABI in a short period of time at their own pace. Further evaluation of this method is indicated.