Georgiadis Georgios, Zisis Ioannis-Erineos, Docea Anca Oana, Tsarouhas Konstantinos, Fragkiadoulaki Irene, Mavridis Charalampos, Karavitakis Markos, Stratakis Stavros, Stylianou Kostas, Tsitsimpikou Christina, Calina Daniela, Sofikitis Nikolaos, Tsatsakis Aristidis, Mamoulakis Charalampos
Department of Urology, University General Hospital of Heraklion, University of Crete, Medical School, Heraklion, Crete, Greece.
Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion, Crete 71003, Greece.
J Clin Med. 2020 Apr 29;9(5):1284. doi: 10.3390/jcm9051284.
Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.
急性肾损伤（AKI）与发病率增加、住院时间延长及死亡率上升相关，在高危患者中尤为如此。磷酸二酯酶5抑制剂（PDE5Is）目前作为人类勃起功能障碍的一线治疗药物，已通过多种肾脏保护机制显示出肾脏保护的有益潜力。这项工作的目的是全面概述关于PDE5Is在各种形式的急性肾损伤中的肾脏保护特性的现有文献。按照系统评价和Meta分析的首选报告项目（PRISMA）声明，对1946年至2019年11月的Medline进行了系统检索，以检测所有相关的动物和人体研究。总共纳入83项研究进行定性综合分析。西地那非是研究最广泛的化合物（42项研究），其次是他达拉非（20项研究）、淫羊藿苷（10项研究）、伐地那非（7项研究）、扎普司特（4项研究）和乌地那非（2项研究）。尽管数据有限，尤其是在人类方面，目前仅有两项临床相关研究结果不明确或为阴性，但动物研究结果很有前景。在绝大多数研究中，PDE5Is的肾脏保护作用是明显的，与急性肾损伤的类型和所应用的药物无关。PDE5Is似乎通过多种机制改善急性肾损伤的肾功能/组织病理学改变，主要是通过影响局部血流动力学、细胞表达以及线粒体对氧化应激和炎症的反应。
