Providence Medical Research Center, Sacred Heart Medical Center, Spokane, WA 99204, USA.
Am J Ther. 2010 Nov-Dec;17(6):553-8. doi: 10.1097/MJT.0b013e3181b96c27.
Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-β₁ excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-β₁.
糖基化终产物（AGEs）是促炎介质，参与糖尿病肾病（DKD）的发病机制。在这项研究中，评估了血管紧张素受体阻断剂对 DKD 患者尿 AGEs 的剂量依赖性影响。将 2 型糖尿病伴蛋白尿≥500mg/d 的患者（n=11）与无 DKD 的糖尿病对照者（n=10）和正常对照者（n=11）进行比较。经过 2 周的洗脱期后，DKD 参与者接受坎地沙坦剂量逐渐增加，从 8、16、32、64mg/d，每 3 周递增一次，共 12 周。其他降压药物进行调整以维持血压稳定。在基线和每个给药期后，进行血压测量和 24 小时尿液采集。尿羧甲基赖氨酸，AGE 生物标志物，在 12 周的剂量递增方案中逐渐减少（r=0.38，P=0.01）。肌酐清除率略有增加，但坎地沙坦给药对白蛋白尿无影响。DKD 参与者的尿转化生长因子-β₁排泄量低于对照者，在研究期间未发生变化。减少肾脏对 AGEs 的暴露可能是血管紧张素受体阻断剂在 DKD 中的保护机制。AGEs 也可能通过与转化生长因子-β₁无关的机制影响糖尿病肾脏。
