Pirfenidone for Diabetic Nephropathy
Pirfenidone for Diabetic Nephropathy
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DOI：
10.1681/asn.2010101049
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发表时间：
2011-06-01
影响因子：
13.6
通讯作者：
Kopp, Jeffrey B.
中科院分区：
文献类型：
--
作者：
Sharma, Kumar;Ix, Joachim H.;Kopp, Jeffrey B.
吡非尼酮是一种口服抗纤维化药物，在动物模型中有益于糖尿病肾病，但它是否对人类糖尿病肾病有效尚不清楚。我们对77名糖尿病肾病患者进行了一项随机、双盲、安慰剂对照研究，这些患者的蛋白尿升高，估计GFR（eGFR）降低（20至75 ml/min/1.73 m2）。预先规定的主要结局是治疗1年后eGFR的变化。我们将26例受试者随机分配至安慰剂组，26例接受1200 mg/d吡非尼酮组，25例接受2400 mg/d吡非尼酮组。在完成研究的52例受试者中，吡非尼酮1200 mg/d组的平均eGFR增加（+3.3 +/- 8.5 ml/min/1.73 m2），而安慰剂组的平均eGFR降低（-2.2 +/- 4.8 ml/min/1.73 m2;与吡非尼酮1200 mg/d组相比，P = 0.026）。吡非尼酮2400 mg/d组的脱落率较高（11/25），eGFR的变化与安慰剂组无显著差异（-1.9 +/- 6.7 ml/min/1.73 m2）。在77例受试者中，安慰剂组4例、吡非尼酮2400 mg/d组1例和吡非尼酮1200 mg/d组在研究期间开始血液透析（P = 0.25）。炎症和纤维化的血浆生物标志物的基线水平与基线eGFR显著相关，但不能预测对治疗的反应。总之，这些结果表明吡非尼酮是治疗显性糖尿病肾病患者的一种有前途的药物。
Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m(2)). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (+3.3 +/- 8.5 ml/min per 1.73 m(2)) whereas the mean eGFR decreased in the placebo group (-2.2 +/- 4.8 ml/min per 1.73 m(2); P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 +/- 6.7 ml/min per 1.73 m(2)). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.