ABSTRACT
BACKGROUND: Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management. METHODS: Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient's plasma (quantity; copies/mL). RESULTS: In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase). CONCLUSIONS: dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.
Subject(s)
Cell-Free Nucleic Acids , Graft Rejection , Kidney Transplantation , Pancreas Transplantation , Biomarkers , Cell-Free Nucleic Acids/genetics , Graft Rejection/diagnosis , Graft Rejection/genetics , Humans , Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Pilot Projects , Postoperative Complications , Tissue DonorsABSTRACT
Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía.
Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.
