Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Diabetes Centre, Khoo Teck Puat Hospital, Singapore, Singapore.
Curr Opin Nephrol Hypertens. 2024 Jan 1;33(1):13-25. doi: 10.1097/MNH.0000000000000935. Epub 2023 Oct 25.
The purpose of this review is to summarize the latest evidence on the prevention and progression of diabetic kidney disease (DKD), as well as novel pharmacological interventions from preclinical and early clinical studies with promising findings in the reduction of this condition's burden.
We will cover the latest evidence on the reduction of proteinuria and kidney function decline in DKD achieved through established renin-angiotensin-aldosterone system (RAAS) system blockade and the more recent addition of SGLT2i, nonsteroidal mineralocorticoid receptor antagonists (MRAs) and GLP1-RA, that combined will most likely integrate the mainstay for current DKD treatment. We also highlight evidence from new mechanisms of action in DKD, including other haemodynamic anti-inflammatory and antifibrotic interventions, oxidative stress modulators and cell identity and epigenetic targets.
Renal specific outcome trials have become more popular and are increasing the available armamentarium to diminish the progression of renal decline in patients at greater risk of end-stage kidney disease (ESKD) such as diabetic individuals. A combined pharmaceutical approach based on available rigorous studies should include RAAS blockade, SGLT2 inhibitors, nonsteroidal MRA and expectedly GLP1-RA on a personalized based-intervention. New specific trials designed to address renal outcomes will be needed for innovative therapies to conclude on their potential benefits in DKD.
本综述旨在总结糖尿病肾病（DKD）预防和进展的最新证据，以及来自临床前和早期临床试验的新型药理学干预措施，这些措施在减轻该疾病负担方面具有有前景的发现。
我们将涵盖通过既定的肾素-血管紧张素-醛固酮系统（RAAS）系统阻断以及最近添加的 SGLT2i、非甾体类盐皮质激素受体拮抗剂（MRAs）和 GLP1-RA 来减少 DKD 蛋白尿和肾功能下降的最新证据，这些联合治疗很可能成为当前 DKD 治疗的主要方法。我们还强调了 DKD 新作用机制的证据，包括其他血流动力学抗炎和抗纤维化干预、氧化应激调节剂以及细胞特性和表观遗传靶点。
肾脏特异性结局试验变得越来越流行，并且正在增加可用的手段来减少处于终末期肾病（ESKD）风险更高的患者（如糖尿病患者）的肾脏衰退进展。基于现有严格研究的联合药物治疗方法应包括 RAAS 阻断、SGLT2 抑制剂、非甾体 MRA 和预计 GLP1-RA，基于个性化干预。需要新的专门试验来解决肾脏结局，以确定创新疗法在 DKD 中的潜在益处。
