Role of Contrast-Enhanced Ultrasound in the Follow-up of Kidney Transplant Patients.

BACKGROUND: Contrast-enhanced ultrasound combines the advantages of native ultrasound and other contrast-enhanced imaging modalities. In selected cases it can be preferable to computerized tomographic scan among kidney transplant recipients. METHODS: We performed a retrospective study involving patients of Semmelweis University Department of Transplantation and Surgery who underwent contrast-enhanced ultrasound examination from 2011 to 2015. During this period, 251 examinations were performed, including 45 on kidney transplant patients. A Toshiba Aplio XU ultrasound device was used, and 1-1.5 mL contrast agent (Sonovue) was administered intravenously for each patient. The indications of these evaluations can be divided into 3 groups: characterization of circumscribed kidney lesions, control after radiofrequency ablation therapy, and examination of graft perfusion. RESULTS: Fully 93% of the examinations were conclusive. In the 1st group of the 37 cases where tumor-suspect lesions were investigated, 13 examinations suggested the presence of a space-occupying lesion. Of those 13 cases, 2 patients had a negative biopsy, nephrectomy was performed in 11 cases, and histologic evaluation verified a tumor in 8 samples. In the 2nd group, the ablation control examination detected a residual tumor in none of the 6 cases. Finally, in 1 of the 2 grafts where the circulation was investigated, blood flow was satisfactory, and in the other it was low. CONCLUSIONS: The contrast-enhanced ultrasound examination was conclusive in most cases. The applied contrast material is not nephrotoxic, and the method uses nonionizing radiation. These features make contrast-enhanced ultrasound highly suitable for the examination of kidney transplant patients.

AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase.

N-{[5-(methanesulfonyl)pyridin-2-yl]methyl}-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (AZD9668) is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. In vitro and in vivo experiments were done to evaluate the binding kinetics, potency, and selectivity of AZD9668, its effects in whole-blood and cell-based assays, and its efficacy in models of lung inflammation and damage. In contrast to earlier NE inhibitors, the interaction between AZD9668 and NE was rapidly reversible. AZD9668 was also highly selective for NE over other neutrophil-derived serine proteases. In cell-based assays, AZD9668 inhibited plasma NE activity in zymosan-stimulated whole blood. In isolated human polymorphonuclear cells, AZD9668 inhibited NE activity on the surface of stimulated cells and in the supernatant of primed, stimulated cells. AZD9668 showed good crossover potency to NE from other species. Oral administration of AZD9668 to mice or rats prevented human NE-induced lung injury, measured by lung hemorrhage, and an increase in matrix protein degradation products in bronchoalveolar lavage (BAL) fluid. In an acute smoke model, AZD9668 reduced the inflammatory response to cigarette smoke as indicated by a reduction in BAL neutrophils and interleukin-1ß. Finally, AZD9668 prevented airspace enlargement and small airway wall remodeling in guinea pigs in response to chronic tobacco smoke exposure whether dosed therapeutically or prophylactically. In summary, AZD9668 has the potential to reduce lung inflammation and the associated structural and functional changes in human diseases.