Amore A, Camilla R, Rollino C, Avenatti E, Campolo F, Peruzzi L, Conti G, Coppo R
S.C. Nefrologia Dialisi Trapianto, Policlinico Universitario Regina Margherita, Torino, Italy.
G Ital Nefrol. 2008 Nov-Dec;25 Suppl 44:53-63.
With its aging population, the Western world is experiencing a significant increase in the prevalence of chronic kidney disease, which has actually been defined as ''pandemic''. The high mortality and comorbidity, especially in terms of cardiovascular disease, have led to a significant increase in hospitalizations and rising public health expenditure, setting a trend that will become unsustainable in the next decades, even in the most developed countries. These epidemiological data have underlined the need for prevention campaigns and urged researchers and clinicians to develop new and more specific treatments able to slow down the progression of chronic kidney disease towards dialysis. To obtain such results, a deeper understanding of the pathogenetic mechanisms of nephropathy progression is mandatory. Once sclerosis is established and the initial pathogenetic noxa, whether or not involving the glomeruli, has been extinguished, the sclerotic progression of different nephropathies follows a standard pathway, irrespective of the initial cause. The achievement of an effective therapy for this condition, in native kidneys as well as transplanted organs, is the third-millennium challenge for nephrologists. In this review we will first describe the main risk factors and pathogenetic mechanisms involved in nephropathy progression and then discuss the results obtained with drugs that basic research has identified as potentially useful in experimental animal models as well as rigorous clinical trials.
随着人口老龄化,西方世界慢性肾脏病的患病率显著上升,实际上已被定义为“大流行”。高死亡率和合并症,尤其是心血管疾病方面的合并症,导致住院率大幅上升和公共卫生支出增加,这一趋势在未来几十年将变得不可持续,即使在最发达国家也是如此。这些流行病学数据凸显了开展预防运动的必要性,并促使研究人员和临床医生开发新的、更具针对性的治疗方法,以减缓慢性肾脏病向透析发展的进程。为了取得这样的成果,深入了解肾病进展的发病机制是必不可少的。一旦硬化形成,且初始致病因素(无论是否涉及肾小球)已消除,不同肾病的硬化进展遵循标准途径,与初始病因无关。在天然肾脏以及移植器官中实现针对这种情况的有效治疗,是肾脏病学家在第三个千年面临的挑战。在这篇综述中,我们将首先描述肾病进展中涉及的主要危险因素和发病机制,然后讨论基础研究确定在实验动物模型以及严格的临床试验中可能有用的药物所取得的结果。