Pyridorin in Type 2 Diabetic Nephropathy
Pyridorin in Type 2 Diabetic Nephropathy
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DOI：
10.1681/asn.2011030272
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发表时间：
2012-01-01
影响因子：
13.6
通讯作者：
Lewis, Julia B.
中科院分区：
文献类型：
--
作者：
Lewis, Edmund J.;Greene, Tom;Lewis, Julia B.
Pyridoxamine dihydrochloride （Pyridorin, NephroGenex）抑制晚期糖基化终产物的形成，清除活性氧和有毒羰基，但这些作用是否转化为肾保护作用尚不清楚。在这项双盲、随机、安慰剂对照试验中，我们随机分配了317例蛋白尿型2型糖尿病肾病患者，每天两次服用安慰剂；吡哆啉，150毫克，每日两次；或吡哆啉，300毫克，每日两次，持续52周。基线时，平均年龄+/- SD为63.9 +/- 9.5岁，平均糖尿病病程为17.6 +/- 8.5年；平均血清肌酐水平为2.2 +/- 0.6 mg/dl，平均蛋白/肌酐比值为2973 +/- 1932 mg/g。关于主要终点，与安慰剂相比，Pyridorin组的血清肌酐从基线到52周的统计学显著变化并不明显。然而，协方差分析表明，治疗效果的大小因基线肾功能而异。在基线血清肌酐浓度最低的患者中，吡哆啉治疗与52周时较低的血清肌酐浓度平均变化相关（安慰剂组、吡哆啉150 mg组和吡哆啉300 mg组分别为0.28、0.07和0.14 mg/dl；吡哆啉剂量与安慰剂相比P=0.05）；没有证据表明在中上两层有显著的处理效果。总之，该试验未能检测到吡哆啉对1年后血清肌酐进展的影响，尽管它表明肾功能损害较小的患者可能受益。
Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls, but whether these actions translate into renoprotective effects is unknown. In this double-blind, randomized, placebo-controlled trial, we randomly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo; Pyridorin, 150 mg twice daily; or Pyridorin, 300 mg twice daily, for 52 weeks. At baseline, the mean age +/- SD was 63.9 +/- 9.5 years, and the mean duration of diabetes was 17.6 +/- 8.5 years; the mean serum creatinine level was 2.2 +/- 0.6 mg/dl, and the mean protein-to-creatinine ratio was 2973 +/- 1932 mg/g. Regarding the primary end point, a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo. However, analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function. Among patients in the lowest tertile of baseline serum creatinine concentration, treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks (0.28, 0.07, and 0.14 mg/dl for placebo, Pyridorin 150 mg, and Pyridorin 300 mg, respectively; P=0.05 for either Pyridorin dose versus placebo); there was no evidence of a significant treatment effect in the middle or upper tertiles. In conclusion, this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year, although it suggests that patients with less renal impairment might benefit.