达格列净减缓高血压合并慢性肾脏病患者从衰弱前期向衰弱的进展。
完整摘要 · 中文译文
背景：慢性肾脏病（CKD）与高血压共享共同的病理生理通路，导致血管损伤、内皮功能障碍和体能下降，尤其是在处于衰弱前期的老年人中。为评估合并CKD的高血压老年患者中肾损伤、体能表现与衰弱进展之间的关系，并评估达格列净是否与减缓衰弱进展相关，我们设计了DAPA-FORTRESS研究（达格列净与高血压和慢性肾脏病中的衰弱进展）。方法：我们入组了135例年龄>65岁、处于衰弱前期的合并CKD的高血压患者，并随访1年。经过粗化精确匹配后，我们的平衡队列有105例患者（52例接受达格列净）。使用相关性和回归模型分析白蛋白尿、估算肾小球滤过率（eGFR）与体能表现之间的关联。使用多变量逻辑回归评估达格列净对衰弱进展的影响。结果：观察到步速与白蛋白尿之间呈显著负相关（r2 = 0.48，P < 0.0001），步速与eGFR之间呈显著正线性相关（r2 = 0.18；P < 0.0001）。eGFR <60 mL/min/1.73 m2的患者体能表现显著差于eGFR较高的患者（P = 0.0003）。在调整分析中，接受达格列净与1年时进展为衰弱的几率较低独立相关（OR = 0.130；CI 0.045-0.381；P < 0.001）。结论：在合并CKD的老年高血压患者中，肾损伤程度越大与 与较差的身体表现相关，而使用达格列净可降低衰弱进展的风险。这些发现表明，钠-葡萄糖协同转运蛋白2抑制剂在这一高危人群中可能对减轻功能衰退具有保护作用。资助：美国国立卫生研究院（NIH）：国家心肺血液研究所（R01-HL146691）、国家糖尿病、消化和肾脏疾病研究所（R01-DK123259）；美国心脏协会（AHA-24IPA1268813、AHA-22-915561、AHA-24-1195524）。
完整摘要 · 英文原文
BACKGROUNDChronic kidney disease (CKD) and hypertension share common pathophysiological pathways contributing to vascular damage, endothelial dysfunction, and physical decline, particularly in older adults with prefrailty. To evaluate the relationship among renal injury, physical performance, and frailty progression in hypertensive older adults with CKD and assess whether dapagliflozin associates with reduced frailty progression, we designed the study DAPA-FORTRESS (DAPAgliflozin and Frailty prOgression in hypeRTension and chRonic kidnEy diSeaSe).METHODSWe enrolled 135 prefrail hypertensive patients with CKD aged >65 years and followed them for 1 year. After coarsened exact matching, our balanced cohort had 105 patients (52 dapagliflozin). Associations between albuminuria, estimated glomerular filtration rate (eGFR), and physical performance were analyzed using correlation and regression models. Effect of dapagliflozin on frailty progression was evaluated using multivariable logistic regression.RESULTSA significant inverse association between gait speed and albuminuria (r2 = 0.48, P < 0.0001) and significant positive linear association between gait speed and eGFR (r2 = 0.18; P < 0.0001) were observed. Patients with eGFR <60 mL/min/1.73 m2 exhibited significantly worse physical performance than those with higher eGFR (P = 0.0003). In adjusted analyses, receiving dapagliflozin was independently associated with lower odds of progressing to frailty at 1 year (OR = 0.130; CI 0.045-0.381; P < 0.001).CONCLUSIONIn older hypertensive patients with CKD, greater renal injury is associated with worse physical performance, while dapagliflozin use reduces the risk of frailty progression. These findings indicate a potential protective role of sodium-glucose cotransporter 2 inhibition in mitigating functional decline in this high-risk population.FUNDINGNIH: National Heart, Lung, and Blood Institute (R01-HL146691), National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK123259); American Heart Association (AHA- 24IPA1268813, AHA-22-915561, AHA-24-1195524).