Baker IDI Heart and Diabetes Institute, St Kilda Rd Central, PO Box 6492, Melbourne, VIC 8008, Australia.
Expert Opin Emerg Drugs. 2013 Mar;18(1):55-70. doi: 10.1517/14728214.2013.762356. Epub 2013 Jan 21.
The need for new approaches to manage the increasing numbers of patients with diabetes and their burden of complications is urgent. Of these, chronic kidney disease imposes some of the highest costs, both in dollars and in terms of human suffering. In individuals with diabetes, the presence and severity of kidney disease adversely affects their well-being, contributes to disease morbidity and increases their risk of a premature death.
To collect information for the strategies previously or currently under investigation for managing kidney disease in patients with diabetes, a literature search was performed through the search engines PubMed and ClinicalTrials.gov.
Despite advancing knowledge on the pathogenesis of diabetic kidney disease, and promising effects in experimental models, at present there are no new drugs that come close to providing the solutions we desire for our patients. Even when used in combination with standard care, renal complications are at best only modestly reduced, at the considerable expense of additional pill burden and exposure to serious off-target effects. Some of the most exciting advances over the last decade, including thiazolidinediones, direct renin inhibitors, endothelin antagonists and most recently bardoxolone methyl have all fallen at this last hurdle. Better targeted ('smarter') drugs appear to be the best hope for renoprotective therapy.
对于糖尿病患者及其并发症负担不断增加的情况，急需寻求新的方法来进行管理。在这些并发症中，慢性肾病带来的经济和人力负担最大。在糖尿病患者中，肾脏疾病的发生和严重程度会对其健康状况产生不利影响，导致疾病发病率上升，并增加其过早死亡的风险。
为了收集糖尿病患者肾病管理中以前或正在研究的策略的信息，通过 PubMed 和 ClinicalTrials.gov 搜索引擎进行了文献检索。
尽管对糖尿病肾病发病机制的认识有所提高，实验模型中也有可喜的效果，但目前尚无接近我们为患者所期望的解决方案的新药。即使与标准护理联合使用，肾脏并发症也只能得到适度的改善，而额外的药物负担和出现严重的脱靶效应的风险却大大增加。过去十年中最令人兴奋的一些进展，包括噻唑烷二酮类、直接肾素抑制剂、内皮素拮抗剂，以及最近的 bardoxolone 甲基，都在这最后一道门槛上失败了。更好的靶向（“更智能”）药物似乎是肾脏保护治疗的最佳希望。
