Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Diabetes. 2021 Jan;70(1):39-50. doi: 10.2337/dbi19-0038.
In diabetes, increasing albuminuria and decreasing glomerular filtration rate are hallmarks of chronic kidney disease in diabetes and increase the risk of atherosclerotic cardiovascular events and mortality as well as the risk for end-stage kidney disease. For two decades, standard of care has been controlling risk factors, such as glucose, blood pressure, lipids, and lifestyle factors, and specifically use of agents blocking the renin-angiotensin system. This has improved outcome, but a large unmet need has been obvious. After many failed attempts to advance the therapeutic options, the past few years have provided several new promising treatment options such as sodium-glucose cotransporter 2 inhibitors, endothelin receptor antagonists, glucagon-like peptide 1 agonists, and nonsteroidal mineralocorticoid receptor antagonists. The benefits and side effects of these agents demonstrate the link between kidney and heart; some have beneficial effects on both, whereas for other potentially renoprotective agents, development of heart failure has been a limiting factor. They work on different pathways such as hemodynamic, metabolic, inflammatory, and fibrotic targets. We propose that treatment may be personalized if biomarkers or physiological investigations assessing activity in these pathways are applied. This could potentially pave the way for precision medicine, where treatment is optimized for maximal benefit and minimal adverse outcomes. At least it may help prioritizing agents for an individual subject.
在糖尿病中，白蛋白尿增加和肾小球滤过率降低是糖尿病慢性肾脏病的标志，增加了动脉粥样硬化性心血管事件和死亡的风险以及终末期肾病的风险。二十年来，标准的治疗方法一直是控制风险因素，如血糖、血压、血脂和生活方式因素，并特别使用抑制肾素-血管紧张素系统的药物。这改善了预后，但明显存在未满足的巨大需求。在多次尝试推进治疗选择失败后，过去几年提供了几种新的有前途的治疗选择，如钠-葡萄糖共转运蛋白 2 抑制剂、内皮素受体拮抗剂、胰高血糖素样肽 1 激动剂和非甾体类盐皮质激素受体拮抗剂。这些药物的益处和副作用表明了肾脏和心脏之间的联系；有些对两者都有有益的影响，而对于其他潜在的肾脏保护剂，心力衰竭的发展一直是一个限制因素。它们作用于不同的途径，如血流动力学、代谢、炎症和纤维化靶点。我们提出，如果应用评估这些途径活性的生物标志物或生理研究来进行治疗，那么治疗可能是个性化的。这可能为精准医学铺平道路，在这种医学中，治疗被优化以实现最大的益处和最小的不良后果。至少，它可能有助于为个别患者确定治疗药物的优先级。
