Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Circ Cardiovasc Interv. 2010 Aug;3(4):376-83. doi: 10.1161/CIRCINTERVENTIONS.110.951277. Epub 2010 Jun 29.
Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA.
RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis.
Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.
经皮腔内肾血管成形术（PTRA）是解决肾动脉狭窄（RAS）的最常见治疗方法。然而，只有 30%的病例肾功能恢复。这些不良结果的原因尚不清楚。我们假设保留 RAS 远端的肾微循环将改善 PTRA 的反应。
在 28 头猪中诱导 RAS。在 14 头猪中，经肾内注射血管内皮生长因子（VEGF）-165 0.05μg/kg（RAS+VEGF）。6 周后，所有猪均在体内使用超快 CT 评估单肾功能。观察了一半的 RAS 和 RAS+VEGF 猪。另一半接受 PTRA 和重复 VEGF，并在 4 周后重复 CT 研究。然后将猪安乐死，取出狭窄的肾脏，使用 3D 微 CT 重建肾微血管（MV）结构，并定量肾纤维化。RAS 和 RAS+VEGF 中的 RAS 程度和高血压相似。RAS 中肾功能和 MV 密度降低，但 RAS+VEGF 中改善。PTRA 很大程度上解决了 RAS，但 RAS+VEGF+PTRA 比 RAS+PTRA 改善高血压和肾功能更大，伴随着 MV 密度增加 34%和纤维化减少。
狭窄肾脏中 MV 结构和功能的保留改善了 PTRA 的反应，表明肾 MV 完整性在确定 PTRA 的反应中起作用。这项研究表明，肾 MV 的损伤和早期丢失是 RAS 中肾损伤进展的一个重要决定因素，并引发了经常不可逆转的损伤。
