González-Albarrán Olga, Morales Cristóbal, Pérez-Maraver Manuel, Aparicio-Sánchez José Juan, Simó Rafael
Endocrinology and Nutrition Department, Gregorio Marañón Hospital, Madrid, Spain.
Endocrinology and Nutrition Department, Virgen Macarena Hospital, Seville, Spain.
Diabetes Ther. 2022 Jul;13(Suppl 1):35-49. doi: 10.1007/s13300-022-01276-2. Epub 2022 Jun 15.
The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly benefit cardiac function through multifaceted interorgan cross talk, which can break the cardiorenal vicious circle linked to T2D. In this article, we briefly review the different mechanisms of action that may explain the renal beneficial effects of SGLT2i and disclose the results of the key renal outcome trials and the subsequent update of related clinical guidelines.
2型糖尿病（T2D）的管理包括降低血糖水平以及减少心血管和微血管并发症。糖尿病肾病（DKD）被定义为存在蛋白尿、肾小球滤过功能受损或两者兼有，是糖尿病一种隐匿性的微血管并发症，会带来巨大的个人和临床负担。肾功能的逐渐减退和蛋白尿增加会导致心血管事件增多。因此，DKD患者需要全面控制相关的心血管危险因素。糖尿病合并肾功能损害的患者，由于存在禁忌证、不良反应或药代动力学改变，抗糖尿病药物的选择较少。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）通过阻断近端小管中钠和葡萄糖的摄取并促进糖尿，从而降低血糖浓度，这些药物目前在T2D的管理中发挥着重要作用。多项心血管结局试验的结果表明，SGLT2i除了能降低心血管事件和死亡率外，还与肾脏结局的改善有关，这代表了该人群护理方面的一项重大进展。专门的肾脏结局试验证实了SGLT2i在不同肾小球滤过率和蛋白尿水平的肾脏保护作用，即使在非糖尿病慢性肾脏病患者中也是如此。值得注意的是，肾功能的这种改善可能通过多方面的器官间相互作用间接有益于心脏功能，从而打破与T2D相关的心肾恶性循环。在本文中，我们简要回顾了可能解释SGLT2i肾脏有益作用的不同作用机制，并披露了关键肾脏结局试验的结果以及相关临床指南的后续更新情况。
