Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy
Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy
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DOI：
10.1159/000075627
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Wuerth, JP
中科院分区：
文献类型：
--
作者：
Bolton, WK;Cattran, DC;Wuerth, JP
背景/目标：在实验模型中，匹马定抑制晚期糖基化终产物的形成并减缓糖尿病并发症的进展。本研究旨在确定匹马定是否能改善1型（胰岛素依赖型）糖尿病肾病。研究方法：这是一项在690例1型糖尿病、肾病和视网膜病变患者中进行的随机、双盲、安慰剂对照研究。患者接受安慰剂、匹马定150 mg或匹马定300 mg每日两次给药，持续2 - 4年。主要终点是血清肌酐加倍的时间;次要终点包括蛋白尿、肾功能和视网膜病变的评估。结果：26%（61/236）的安慰剂治疗患者和20%（91/454）的匹马定治疗患者的血清肌酐加倍（p = 0.099）。与安慰剂组的9.80 ml/min/1.73 m2相比，匹马定治疗组的肾小球滤过率下降更慢，36个月时较基线下降6.26 ml/min/1.73 m2（p = 0.05），匹马定减少了24小时总尿蛋白尿。（第36个月时，低剂量组较基线的平均降幅为732 mg/24 h，高剂量组为329 mg/24 h，而安慰剂组为35 mg/24 h; p ≤ 0.001。）与接受安慰剂治疗的患者（16%; 28/179）相比，接受吡马定治疗的基线和终点评价患者（31/324; 10%）较少发生视网膜病变（糖尿病视网膜病变早期治疗研究）评分三级或以上进展（p = 0.030）。三名接受高剂量匹马定治疗的患者发生肾小球肾炎，但没有一名接受低剂量治疗的患者发生肾小球肾炎。结论：虽然这项研究没有证明匹马定对1型糖尿病引起的显性肾病进展具有统计学显著的有益作用，但值得注意的是，它提供了第一个临床证据，证明了抑制晚期糖基化终产物形成可导致临床上重要的1型糖尿病严重并发症减轻。版权所有（C）2004 S. Karger AG，巴塞尔。
Background/Aims: Pimagedine inhibits the formation of advanced glycation end products and slows the progression of diabetic complications in experimental models. This study was undertaken to determine if pimagedine ameliorates nephropathy in type 1 ( insulin-dependent) diabetes mellitus. Methods: This was a randomized, double-masked, placebo-controlled study performed in 690 patients with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg for 2 - 4 years. The primary end point was the time to doubling of serum creatinine; the secondary end points included evaluations of proteinuria, kidney function, and retinopathy. Results: Serum creatinine doubled in 26% (61/236) of the placebo-treated patients and in 20% (91/454) of those who received pimagedine ( p = 0.099). The estimated glomerular filtration rate decreased more slowly in the pimagedine-treated patients with a 36-month decrease from baseline of 6.26 ml/min/ 1.73 m(2) as compared with 9.80 ml/ min/1.73 m(2) in the placebo-treated patients ( p = 0.05), and pimagedine reduced the 24-hour total urinary proteinuria. ( The mean reduction from baseline at month 36 was 732 mg/24 h at the low dose and 329 mg/24 h at the high dose as compared with 35 mg/24 h in the placebo group; p less than or equal to 0.001.) Fewer pimagedine-treated patients with baseline and end point evaluations (31/324; 10%) as compared with those receiving placebo (16%; 28/179) experienced a three-step or greater progression of the retinopathy ( Early Treatment of Diabetic Retinopathy Study) score ( p = 0.030). Three patients receiving high-dose pimagedine but none receiving low-dose treatment developed glomerulonephritis. Conclusions: While this study did not demonstrate a statistically significant beneficial effect of pimagedine on the progression of overt nephropathy resulting from type 1 diabetes, it is noteworthy in providing the first clinical proof of the concept that inhibiting advanced glycation end product formation can result in a clinically important attenuation of the serious complications of type 1 diabetes mellitus. Copyright (C) 2004 S. Karger AG, Basel.