Department of Diabetes, Monash University Central, Clinical School, Melbourne, VIC 3004, Australia.
Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, VIC 3004, Australia.
Int J Mol Sci. 2020 Mar 23;21(6):2218. doi: 10.3390/ijms21062218.
The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.
糖尿病肾病 (DKD) 进展的主要临床关联因素是血糖控制和全身高血压。最近的研究继续强调血管活性激素途径,包括醛固酮和内皮素,这表明血管收缩途径在促进糖尿病中的肾脏损害中起关键作用。葡萄糖本身在 DKD 中的作用仍然难以确定,但似乎涉及包括活性氧 (ROS) 和二羰基化合物(如甲基乙二醛)在内的关键中间产物,这些中间产物激活细胞内途径,促进肾脏纤维化和炎症。最近的研究已经确定了血液动力学和代谢途径之间的一种新的分子相互作用,这可能为 DKD 的新治疗方法提供依据。这将基于 RAAS 阻断的积极结果以及最近更新的新型降糖药物(如 SGLT2 抑制剂和 GLP1 受体激动剂)进一步改善 DKD 的前景。