Perico Norberto, Cortinovis Monica, Remuzzi Giuseppe
G Ital Nefrol. 2016 Sep-Oct;33(5).
Recent advances in the understanding of the molecular mechanisms underlying autosomal dominant polycystic kidney disease (ADPKD) set the stage for the development of various treatments aimed to arrest or delay disease progression. In particular, clinical trials showed that the use of somatostatin analogues in patients with ADPKD is able to slow down the increase in total kidney volume and the progressive decline in renal function over the long-term. Treatment with these agents is generally well tolerated and it also enables to control cyst growth in the liver in patients with this extra-renal manifestation of the disease. By contrast, mammalian target of rapamycin (mTOR) inhibitors, although promising in different experimental models of kidney and liver disease, in most clinical studies they were not effective in slowing cystic kidney growth and/or improving the progressive renal function decline in patients with ADPKD. Therapy with mTOR inhibitors is also limited by the elevated incidence of adverse events, which frequently requires drug withdrawal or dose reduction, eventually nullifying the potential renoprotective effect.
对常染色体显性多囊肾病(ADPKD)潜在分子机制认识的最新进展为开发旨在阻止或延缓疾病进展的各种治疗方法奠定了基础。特别是,临床试验表明,在ADPKD患者中使用生长抑素类似物能够长期减缓总肾体积的增加以及肾功能的渐进性下降。这些药物的治疗通常耐受性良好,并且还能够控制患有这种疾病肾外表现的患者肝脏中的囊肿生长。相比之下,雷帕霉素靶蛋白(mTOR)抑制剂虽然在不同的肾脏和肝脏疾病实验模型中很有前景,但在大多数临床研究中,它们在减缓ADPKD患者的多囊肾生长和/或改善进行性肾功能下降方面并不有效。mTOR抑制剂治疗还受到不良事件发生率升高的限制,这经常需要停药或减药,最终抵消了潜在的肾脏保护作用。