Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Department of Pathophysiology, Medicine, Charles University, Prague, Czech Republic.
Clin Exp Hypertens. 2021 Aug 18;43(6):522-535. doi: 10.1080/10641963.2021.1907398. Epub 2021 Mar 30.
The coincidence of congestive heart failure (CHF) and chronic kidney disease (CKD) results in poor survival rate. The aim of the study was to examine if renal denervation (RDN) would improve the survival rate in CHF induced by creation of aorto-caval fistula (ACF). Fawn-hooded hypertensive rats (FHH), a genetic model of spontaneous hypertension associated with CKD development, were used. Fawn-hooded low-pressure rats (FHL), without CKD, served as controls. RDN was performed 4 weeks after creation of ACF and the follow-up period was 10 weeks. We found that intact (non-denervated) ACF FHH exhibited survival rate of 58.8% (20 out of 34 rats), significantly lower than in intact ACF FHL (81.3%, 26/32 rats). In intact ACF FHL albuminuria remained stable throughout the study, whereas in ACF FHH it increased significantly, up to a level 40-fold higher than the basal values. ACF FHL did not show increases in renal glomerular and tubulointerstitial injury as compared with FHL, while ACF FHH exhibited marked increases in kidney injury as compared with FHH. RDN did not improve the survival rate in either ACF FHL or ACF FHH and did not alter the course of albuminuria in ACF FHL. RDN attenuated the albuminuria, but did not reduce the kidney injury in ACF FHH. Our present results support the notion that even modest CKD increases CHF-related mortality. RDN did not attenuate CHF-dependent mortality in ACF FHH, it delayed the progressive rise in albuminuria, but it did not reduce the degree of kidney injury.
充血性心力衰竭 (CHF) 和慢性肾脏病 (CKD) 的同时发生导致生存率降低。本研究旨在探讨肾去神经支配 (RDN) 是否会改善因创建腔静脉瘘 (ACF) 而导致的 CHF 的生存率。使用了自发性高血压相关 CKD 发展的遗传模型——小鹿犬高血压大鼠 (FHH)。没有 CKD 的小鹿犬正常血压大鼠 (FHL) 作为对照。在创建 ACF 后 4 周进行 RDN,随访期为 10 周。我们发现,完整 (未去神经支配) 的 ACF FHH 的生存率为 58.8%(34 只大鼠中有 20 只),明显低于完整的 ACF FHL(81.3%,32 只大鼠中有 26 只)。在完整的 ACF FHL 中,白蛋白尿在整个研究过程中保持稳定,而在 ACF FHH 中则显著增加,达到基础值的 40 倍以上。与 FHL 相比,ACF FHH 的肾小球和肾小管间质损伤没有增加,而 ACF FHH 的肾脏损伤明显增加。RDN 既没有改善 ACF FHL 或 ACF FHH 的生存率,也没有改变 ACF FHL 中白蛋白尿的病程。RDN 减轻了白蛋白尿,但没有减轻 ACF FHH 的肾脏损伤。我们目前的结果支持这样一种观点,即即使是轻度的 CKD 也会增加 CHF 相关的死亡率。RDN 并没有减轻 ACF FHH 中 CHF 相关的死亡率,它延迟了白蛋白尿的逐渐升高,但没有降低肾脏损伤的程度。