Supplementary Material for: Endostatin Is an Independent Risk Factor of Graft Loss after Kidney Transplant

<b><i>Background:</i></b> Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. <b><i>Methods:</i></b> We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. <b><i>Results:</i></b> Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71–0.86, <i>p</i> &lt; 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss (<i>p</i> &lt; 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19–31.72; <i>p</i> = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. <b><i>Conclusion:</i></b> Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.

背景：内皮抑素（Endostatin）是 XVIII型胶原蛋白（collagen XVIII）的20 kDa C端片段，其已知功能为抑制毛细血管内皮细胞增殖。既往研究提示，循环内皮抑素可独立预测新发慢性肾脏病的发生风险。然而，内皮抑素对肾移植受者（kidney transplant recipients, KTRs）移植物丢失的影响尚不清楚。
方法：本研究纳入574名维持性肾移植受者，开展前瞻性观察队列研究。中位随访时长为48个月，随访期间记录受试者的肾移植物丢失与全因死亡结局。于基线时采集血清、尿液样本及临床资料，采用酶联免疫吸附试验（ELISA）检测血清内皮抑素浓度。
结果：574名受试者中，共37例发生移植物丢失，62例死亡。针对移植物丢失结局，受试者工作特征曲线（receiver operating characteristics, ROC）分析显示，内皮抑素的最佳截断值为147.3 pmol/L，曲线下面积为0.79（95%CI 0.71~0.86，p < 0.001）。Kaplan-Meier曲线分析显示，血清内皮抑素浓度升高与移植物丢失风险呈正相关（p < 0.001）。多变量Cox回归分析显示，在校正移植物丢失相关危险因素后，基线内皮抑素浓度仍与移植物丢失显著相关（校正后风险比（hazard ratio, HR）8.34；95%CI 2.19~31.72；p = 0.002）。经典移植物丢失危险因素（如基线估算肾小球滤过率（estimated glomerular filtration rate）、尿蛋白排泄量）的校正后HR值相对更低（分别为1.91与5.44）。与移植物丢失结局不同，基线内皮抑素浓度与全因死亡无显著关联。
结论：肾移植受者基线时的血清内皮抑素水平升高，与移植物丢失风险独立相关。