Division of Nephrology, University of Utah Health Sciences Center, 1900 East 30 North, Salt Lake City, UT 84132, USA.
J Am Soc Nephrol. 2011 Apr;22(4):763-72. doi: 10.1681/ASN.2010080869. Epub 2011 Mar 3.
Although endothelin-receptor antagonists reduce albuminuria in diabetic nephropathy, fluid retention limits their use. Here, we examined the effect of atrasentan, a selective endothelin A receptor (ET(A)R) antagonist, on albuminuria in a randomized, double-blind, placebo-controlled trial of subjects with diabetic nephropathy already receiving stable doses of renin-angiotensin system (RAS) inhibitors. We randomly assigned 89 subjects with eGFR >20 ml/min per 1.73 m(2) and a urinary albumin-to-creatinine ratio (UACR) of 100 to 3000 mg/g to placebo or atrasentan (0.25, 0.75, or 1.75 mg daily) for 8 weeks. Compared with placebo, atrasentan significantly reduced UACR only in the 0.75- and 1.75-mg groups (P=0.001 and P=0.011, respectively). Compared with the 11% reduction in the geometric mean of the UACR from baseline to final observation in the placebo group during the study, the geometric mean of UACR decreased by 21, 42, and 35% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups (P=0.291, P=0.023, and P=0.073, respectively). In the placebo group, 17% of subjects achieved ≥40% reduction in UACR from baseline compared with 30, 50, and 38% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups, respectively (P=0.029 for 0.75 mg versus placebo). Peripheral edema occurred in 9% of subjects receiving placebo and in 14, 18, and 46% of those receiving 0.25, 0.5, and 1.75 mg atrasentan, respectively (P=0.007 for 1.75 mg versus placebo). In summary, atrasentan, at the doses tested, is generally safe and effective in reducing residual albuminuria and may ultimately improve renal outcomes in patients with type 2 diabetic nephropathy.
虽然内皮素受体拮抗剂可降低糖尿病肾病患者的蛋白尿，但液体潴留限制了其应用。在此，我们在已经接受肾素-血管紧张素系统（RAS）抑制剂稳定剂量治疗的糖尿病肾病患者中，进行了一项随机、双盲、安慰剂对照试验，以评估选择性内皮素 A 受体（ET(A)R）拮抗剂阿曲生坦对蛋白尿的影响。我们将 89 名 eGFR>20 ml/min/1.73 m² 且尿白蛋白/肌酐比值（UACR）为 100 至 3000 mg/g 的患者随机分为安慰剂组或阿曲生坦组（每日 0.25、0.75 或 1.75 mg），治疗 8 周。与安慰剂相比，阿曲生坦仅在 0.75 和 1.75 mg 组显著降低 UACR（P=0.001 和 P=0.011）。与研究期间安慰剂组 UACR 从基线到最终观察的几何均数降低 11%相比，阿曲生坦 0.25、0.75 和 1.75 mg 组 UACR 的几何均数分别降低了 21%、42%和 35%（P=0.291、P=0.023 和 P=0.073）。安慰剂组中有 17%的患者 UACR 从基线降低≥40%，而阿曲生坦 0.25、0.75 和 1.75 mg 组分别有 30%、50%和 38%的患者 UACR 降低≥40%（P=0.029，与 0.75 mg 安慰剂相比）。接受安慰剂的患者中有 9%发生外周水肿，而接受 0.25、0.5 和 1.75 mg 阿曲生坦的患者分别有 14%、18%和 46%发生外周水肿（P=0.007，与 1.75 mg 安慰剂相比）。总之，在研究剂量下，阿曲生坦通常安全有效，可降低残余蛋白尿，最终可能改善 2 型糖尿病肾病患者的肾脏结局。
