Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. Dcbld2 2/2 mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). 18 F-NaF PET/CT can detect the aortic valve calcification process in humans. However, its feasibility in preclinical models of CAVD remains to be determined. Here, we sought to validate 18 F-NaF PET/CT for tracking murine aortic valve calcification and leveraged it to examine the development of calcification with aging and its interdependence with BAV and AS in Dcbld2 2/2 mice. Methods: Dcbld2 2/2 mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, 18 F-NaF PET/CT (n 5 34, or autoradiography (n 5 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (n 5 12). The aortic valve signal was quantified as SUV max on PET/CT and as percentage injected dose per square centimeter on autoradiography. The valve tissue sections were analyzed by microscopy to identify tricuspid and bicuspid aortic valves. Results:The aortic valve 18 F-NaF signal on PET/CT was significantly higher at 18-24 mo (P , 0.0001) and 10-16 mo (P , 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher 18 F-NaF signal than tricuspid aortic valves (P , 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher 18 F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson r 5 0.79, P , 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (P , 0.05). Transaortic valve flow velocity was significantly higher in animals with BAV at all ages. Finally, there was a significant correlation between transaortic valve flow velocity and aortic valve calcification by both PET/CT (r 5 0.55, P , 0.001) and autoradiography (r 5 0.45, P , 0.01). Conclusion: 18 F-NaF PET/CT links valvular calcification to BAV and aging in Dcbld2 2/2 mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, 18 F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.
Introduction: Renovascular hypertension is among the significant causes of severe hypertension in pediatrics. Primary therapeutic approaches, including drug therapy or angioplasty, are not always feasible, and their effectiveness is variable. Meanwhile, several conditions leading to renal function impairment, including severe renal artery stenosis, may represent the respective kidney as an apparently non-functioning organ in various imaging modalities. We aim to demonstrate that the only organ in the body of a child with non-treated renovascular hypertension and severe renal artery stenosis is the ipsilateral non-functioning kidney. This kidney is alive and protected from hypertension by renal artery stenosis. Renal autotransplantation (RAT) can be superior to nephrectomy in such cases to protect from severe hypertension. This phenomenon can be confirmed by controlled hypertension and hypertrophy of transplanted kidney accompanied by shrinkage of contralateral compensatory hypertrophy. Case Presentation: We introduce a 14-year-old child with a history of diagnosed hypertension from seven years ago, presenting with resistance to four-drug therapy. Renal scintigraphy and intravenous pyelography found no activity pertaining to the relative kidney, and angiography exhibited severe stenosis of the renal artery with preserved blood circulation. Renal autotransplantation successfully restored the function of the respective kidney based on pre-and post-surgery intravenous pyelography and decreased the blood pressure to normal limits. Conclusions: Our experience shows we cannot mark a kidney as a "non-functioning" organ only on the basis of the preliminary findings from conventional imaging modalities, including intravenous pyelography, scintigraphy, and duplex ultrasound. Moreover, in cases that angioplasty is failed or is not feasible, renal auto-transplantation may be a safe alternative with promising outcomes in patients with renovascular hypertension, being able to restore the function of the kidney.
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