PDF(Pubmed)
Abstract：
BACKGROUND: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.
METHODS: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).
RESULTS: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.
CONCLUSIONS: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.
METHODS: Sixteen healthy merino ewes were surgically instrumented to enable measurement of mean arterial pressure, cardiac output, renal blood flow, renal cortical and medullary perfusion, and oxygenation. After a 5-day recovery period, sepsis was induced via slow and continuous intravenous infusion of live Escherichia coli. Twenty-three hours later, sheep were randomized to receive an intravenous bolus of 0.2 mg/kg empagliflozin (n = 8) or a fluid-matched vehicle (n = 8).
RESULTS: Empagliflozin treatment did not significantly reduce renal medullary hypoperfusion or hypoxia, improve kidney function, or induce histological changes. Renal cortical oxygenation during the intervention period was 47.6 ± 5.9 mmHg in the empagliflozin group compared with 40.6 ± 8.2 mmHg in the placebo group (P = 0.16). Renal medullary oxygenation was 28.0 ± 18.5 mmHg in the empagliflozin compared with 25.7 ± 16.3 mmHg (P = 0.82). Empagliflozin treatment did not result in significant between-group differences in renal blood flow, kidney function, or renal histopathological changes.
CONCLUSIONS: In a large mammalian model of septic AKI, a single dose of empagliflozin did not improve renal microcirculatory perfusion, oxygenation, kidney function, or histopathology.
摘要：
背景：接受钠-葡萄糖转运蛋白-2抑制剂（SGLT2i）治疗的2型糖尿病患者的急性肾损伤（AKI）发生率较低。脓毒症是危重患者中大多数AKI的原因。这项研究调查了SGLT2i在革兰氏阴性脓毒性AKI的绵羊模型中是否具有肾脏保护作用。
方法：对16只健康的美利诺母羊进行外科手术，以测量平均动脉压，心输出量,肾血流量,肾皮质和髓质灌注，和氧合。经过5天的恢复期，脓毒症是通过缓慢和连续静脉输注活大肠杆菌诱导的。二十三小时后,绵羊随机接受静脉推注0.2mg/kg依帕列净(n=8)或液体匹配载体(n=8).
结果：Empagliflozin治疗并没有显著减少肾髓质灌注不足或缺氧，改善肾功能，或诱导组织学变化。干预期间，依帕列净组的肾皮质氧合为47.6±5.9mmHg，而安慰剂组为40.6±8.2mmHg（P=0.16）。empagliflozin的肾脏髓质氧合为28.0±18.5mmHg，而25.7±16.3mmHg（P=0.82）。Empagliflozin治疗并没有导致肾血流量的显著组间差异，肾功能,或肾组织病理学改变。
结论：在脓毒症AKI的大型哺乳动物模型中，单剂量的依帕列净并不能改善肾脏微循环灌注，氧合，肾功能,或组织病理学。
方法：对16只健康的美利诺母羊进行外科手术，以测量平均动脉压，心输出量,肾血流量,肾皮质和髓质灌注，和氧合。经过5天的恢复期，脓毒症是通过缓慢和连续静脉输注活大肠杆菌诱导的。二十三小时后,绵羊随机接受静脉推注0.2mg/kg依帕列净(n=8)或液体匹配载体(n=8).
结果：Empagliflozin治疗并没有显著减少肾髓质灌注不足或缺氧，改善肾功能，或诱导组织学变化。干预期间，依帕列净组的肾皮质氧合为47.6±5.9mmHg，而安慰剂组为40.6±8.2mmHg（P=0.16）。empagliflozin的肾脏髓质氧合为28.0±18.5mmHg，而25.7±16.3mmHg（P=0.82）。Empagliflozin治疗并没有导致肾血流量的显著组间差异，肾功能,或肾组织病理学改变。
结论：在脓毒症AKI的大型哺乳动物模型中，单剂量的依帕列净并不能改善肾脏微循环灌注，氧合，肾功能,或组织病理学。
