Benvenuto Manuela, Panzarella Gaetano, Shehaj Ermal, Valenti Chiara, Caldarola Pasquale, Colivicchi Furio, Gabrielli Domenico, Iacoviello Massimo
U.O.C Cardiologia-UTIC-Emodinamica, P.O. Giuseppe Mazzini, Teramo.
AOR Villa Sofia-Cervello, P.O. Cervello, Palermo.
G Ital Cardiol (Rome). 2023 Mar;24(3):188-195. doi: 10.1714/3980.39621.
The kidney plays an important role in maintaining glucose homeostasis which is used as a metabolic substrate, generated through the mechanism of gluconeogenesis and reabsorbed in the glomerular filtrate through the action of sodium-glucose cotransporters 1 and 2 (SGLT1/2) located in the proximal tubule. Recent studies have shown that inhibition of renal glucose reabsorption, achieved through the administration of sodium-glucose cotransporter inhibitors, significantly reduces renal adverse events and exacerbations of heart failure, not only in diabetic patients, with and without confirmed cardiovascular damage, but also in patients with advanced chronic renal failure and in patients with heart failure with reduced ejection fraction regardless of the presence of diabetes. The extent of the benefit was relevant in the various clinical conditions studied, and led to a significant reduction in the major adverse cardiovascular outcomes recorded in each study. In all controlled studies, the efficacy of sodium-glucose cotransporter inhibitors was strongly associated with the reduction in progression of renal damage, as evidenced by the significant reduction in overall mortality obtained in the two studies that enrolled populations of diabetic and non-diabetic patients with advanced chronic renal failure. Both studies were stopped early at the interim analysis due to the evident superiority of the therapy in the treated arm.The purpose of this review is to examine the role of SGLT2/1 both in physiological conditions that in the course of cardio-nephropathy associated or not with type 2 diabetes mellitus and the effect of SGLT2/1 inhibition on clinical outcomes in different cardiovascular risk population enrolled in different randomized controlled clinical trials.
肾脏在维持葡萄糖稳态中发挥着重要作用，葡萄糖作为一种代谢底物，通过糖异生机制产生，并通过位于近端小管的钠-葡萄糖协同转运蛋白1和2（SGLT1/2）的作用在肾小球滤液中被重吸收。最近的研究表明，通过给予钠-葡萄糖协同转运蛋白抑制剂来抑制肾脏对葡萄糖的重吸收，不仅在患有和未患有确诊心血管损伤的糖尿病患者中，而且在晚期慢性肾衰竭患者和射血分数降低的心力衰竭患者中（无论是否患有糖尿病），都能显著减少肾脏不良事件和心力衰竭的恶化。在所研究的各种临床情况下，获益程度都很显著，并导致每项研究中记录的主要不良心血管结局显著降低。在所有对照研究中，钠-葡萄糖协同转运蛋白抑制剂的疗效与肾脏损伤进展的减少密切相关，这在两项纳入晚期慢性肾衰竭糖尿病和非糖尿病患者群体的研究中获得的总体死亡率显著降低中得到了证明。由于治疗组的治疗具有明显优势，这两项研究在中期分析时均提前终止。本综述的目的是研究SGLT2/1在与2型糖尿病相关或不相关的心脏-肾病过程中的生理条件下的作用，以及SGLT2/1抑制对不同随机对照临床试验中纳入的不同心血管风险人群临床结局的影响。
