2nd Department of Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 128 00, Prague 2, Czech Republic.
Institute of Physiology, First Faculty of Medicine, Charles University in Prague, Albertov 5, 128 00, Prague 2, Czech Republic.
J Transl Med. 2017 Oct 25;15(1):215. doi: 10.1186/s12967-017-1319-0.
Renal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin-angiotensin-aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury.
An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings.
Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups.
In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.
肾脏去神经支配（RDN）是心脏病学中一种很有前途的治疗方法。目前最受关注的适应症是难治性高血压。其他潜在的适应症包括心房颤动、2 型糖尿病和慢性肾功能不全等。先前的试验结果存在矛盾，但仍在探索 RDN 的真正益处。由于肾交感神经驱动过度激活，肾功能不全和难治性高血压患者被提议成为这种治疗的良好目标。然而，只有有限数量的研究显示这些患者受益。我们假设，在我们的慢性肾脏病（CKD）缺血模型中，由于肾素-血管紧张素-醛固酮系统（RAAS）活性增加，肾脏去神经支配可能具有保护作用，可减缓或阻断肾脏损伤的进展。
采用选择性肾动脉栓塞（残余肾猪模型）建立缺血诱导的慢性肾功能不全实验生物模型。评估了 27 个生物模型。在 19 个生物模型中进行了肾脏去神经支配（去神经组），其余作为对照组（n=8）。通过生化参数和组织学发现比较和评估两组之间的肾脏损伤和修复过程。
在 27 头猪中成功获得并维持了有功能的残余肾生物模型。两组在基线时的生化参数无显著差异。组织学评估证明去神经组中所有生物模型的 RDN 手术均成功。在 7 周的时间内，两组的血清尿素、肌酐和醛固酮浓度均显著升高。两组之间尿素和肌酐水平的差异无统计学意义。然而，与对照组相比，去神经组的醛固酮水平显著降低。肾动脉的组织学评估表明，与仅接受 RAE 的动物相比，RDN 更倾向于对动脉壁造成更多损伤。此外，肾脏的形态损伤，即损伤表面（或疤痕）与肾脏总表面的比例，两组之间也没有显著差异。
在这项研究中，我们未能通过实验室或组织学评估显示 RDN 单独对缺血性肾实质损伤有显著的保护作用。然而，醛固酮水平的变化表明肾脏去神经支配对 RAAS 系统有一定的影响。我们假设 RAAS 和交感神经系统的联合阻断可能会对急性缺血提供更多的保护作用。这需要在未来的研究中进一步探讨。
