Methodist Hospital, Houston, TX, USA.
Clin Transplant. 2011 Jul-Aug;25(4):523-33. doi: 10.1111/j.1399-0012.2010.01295.x. Epub 2010 Jun 22.
Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models.
This randomized 15-center, double-blind, 59-patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated.
No drug-specific toxicities or increased adverse event rates were noted. Two YSPSL-treated patients died of causes determined as unrelated to study drug. YSPSL did not reduce the incidence of dialysis within the first week post-transplant (41% in treated vs. 20% in placebo patients). Renal function endpoints scored at post-operative days 1 & 2 were also not impacted by YSPSL. However, at day 5, the fraction of patients with serum creatinine above 6 mg/dL was lower in the YSPSL vs. placebo group (26% vs. 55%, p = 0.043). Large variations in the dialysis-delayed graft function (DGF) rates were observed between centers, independently of treatment assignment, indicating subjectivity of this endpoint.
In this first Ph2a study in kidney transplantation, YSPSL was safe but did not impact the dialysis-DGF rate. Further studies with more objective efficacy endpoints are required to define the impact of YSPSL on early renal allograft function.
重组 P 选择素糖蛋白配体 IgG 融合蛋白 rPSGL-Ig（YSPSL）是人 P 选择素配体和 IgG1-Fc 的融合蛋白，可阻断白细胞黏附，防止动物模型中的缺血再灌注损伤（IRI）。
这是一项随机的 15 中心、双盲、59 例 2a 期研究，评估了 YSPSL 在接受已故供体肾移植受者中的安全性及其改善早期移植物功能的潜在疗效。评估了两种剂量和两种给药方式。
未观察到药物特异性毒性或不良反应发生率增加。两名 YSPSL 治疗患者因与研究药物无关的原因死亡。YSPSL 并未降低移植后第一周内透析的发生率（治疗组为 41%，安慰剂组为 20%）。YSPSL 也未影响术后第 1 天和第 2 天的肾功能终点。然而，在第 5 天，血清肌酐高于 6mg/dL 的患者比例在 YSPSL 组低于安慰剂组（26% vs. 55%，p=0.043）。各中心之间的透析延迟移植物功能障碍（DGF）发生率存在较大差异，与治疗分配无关，表明该终点存在主观性。
在这项肾移植的首次 2a 期研究中，YSPSL 是安全的，但并未影响透析-DGF 发生率。需要进一步的研究，采用更客观的疗效终点，以确定 YSPSL 对早期肾移植物功能的影响。
