D'Marco Luis, Puchades María Jesús, Gandía Lorena, Forquet Claudia, Giménez-Civera Elena, Panizo Nayara, Reque Javier, Juan-García Isabel, Bermúdez Valmore, Gorriz José Luis
Nephrology Department, Hospital Clínico Universitario, Instituto de Investigación Sanitaria (INCLIVA), Valencia, Spain.
Centro de Estudios Universitarios Cardenal Herrera University, Valencia, Spain.
touchREV Endocrinol. 2021 Nov;17(2):84-87. doi: 10.17925/EE.2021.17.2.84. Epub 2021 Nov 10.
Type 2 diabetes mellitus (T2DM) affects an estimated 463 million people worldwide, equivalent to 1 in 11 adults. Moreover, the rapid growth of this disease has resulted in a high incidence of diabetic kidney disease (DKD), which, together with hypertension, is the main cause of chronic kidney disease (CKD). Hyperglycaemia, low-grade inflammation, altered lipid metabolism and hyperactivation of the renin-angiotensin-aldosterone system (RAAS) seem to be interrelated mechanisms contributing to both T2DM and microvascular complications. The introduction of drugs such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists has improved the ability to slow the progression of DKD, and has also demonstrated benefits in cardiovascular disease. Beyond the effects of these novel antidiabetic drugs, a body of evidence suggests that the overactivation of the mineralocorticoid receptor also contributes to CKD progression. Moreover, new and ongoing trials have demonstrated that the selective nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone improves the risk of CKD progression and cardiovascular events in patients with CKD and T2DM and optimized RAAS blockade. We review the rationale for the development and use of MRA drugs to slow CKD progression in patients with DKD, as well as other pleiotropic effects, and highlight the warnings associated with these agents.
全球约有4.63亿人患有2型糖尿病(T2DM),相当于每11名成年人中就有1人患病。此外,这种疾病的快速增长导致糖尿病肾病(DKD)的高发病率,糖尿病肾病与高血压一起,是慢性肾脏病(CKD)的主要病因。高血糖、低度炎症、脂质代谢改变以及肾素-血管紧张素-醛固酮系统(RAAS)的过度激活似乎是导致T2DM和微血管并发症的相互关联机制。钠-葡萄糖协同转运蛋白2抑制剂和胰高血糖素样肽1受体激动剂等药物的引入,提高了减缓DKD进展的能力,并且在心血管疾病方面也显示出益处。除了这些新型抗糖尿病药物的作用外,大量证据表明盐皮质激素受体的过度激活也会促进CKD的进展。此外,新的和正在进行的试验表明,选择性非甾体盐皮质激素受体拮抗剂(MRA)非奈利酮可降低CKD和T2DM患者以及优化RAAS阻断治疗患者的CKD进展风险和心血管事件风险。我们回顾了开发和使用MRA药物以减缓DKD患者CKD进展的基本原理以及其他多效性作用,并强调了与这些药物相关的警示。