Department of Nephrology and Renal Transplantation, National and Kapodistrian University of Athens, School of Medicine, Laiko Hospital, Athens, Greece.
Eur Rev Med Pharmacol Sci. 2021 Jul;25(14):4762-4772. doi: 10.26355/eurrev_202107_26388.
Various biomarkers have been studied in the early post-kidney transplantation (post-KTx) period in order to identify potential therapeutic targets for improving long-term graft survival. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a biomarker that has recently gained interest in cardiovascular disease but its role still remains to be defined post-KTx.
We prospectively evaluated the levels of PCSK9, interleukin (IL)-6, WBC and C-reactive protein in seventy-three hemodialysis patients undergoing KTx, at 3 time-points; pre-transplantation (day 0) and at 1 and 6-months post-KTx. All data were also analyzed according to donor-type (living or deceased) and compared with hemodialysis patients on transplant waiting list.
At Day 0 there was no difference in WBC, CRP, IL-6 and PCSK9 levels between patients scheduled for transplantation and those who remained on hemodialysis. In transplanted patients WBC, CRP and IL-6 levels were significantly reduced early post-KTx [logIL-6 Day 0: 0.68 (0.33, 0.85) vs. 1-month: 0.57 (0.37, 0.75) vs. 6-months: 0.50 (0.32, 0.69) pg/ml, p=0.01], while PCSK9 levels were significantly increased (Day 0: 199.8±63.0 vs. 1-month: 276.2±79.4 vs. 6-months: 245.9±62.5 ng/ml, p<0.001). In contrast, no change of WBC, CRP, IL-6 and PCSK9 levels was observed in hemodialysis patients on follow-up (p=NS for all). Between living-donor and deceased-donor recipients, analysis showed reduced CRP and increased PCSK9 levels in both groups (p<0.05 for all), while IL-6 levels were reduced in living-donor and increased in deceased-donor recipients 1-month post-KTx. PCSK9 levels were not correlated with renal function, delayed graft function, rejection episodes or inflammatory biomarkers.
PCSK9 levels were increased post-KTx independently from renal function and inflammatory biomarkers, in both living and deceased-donor recipients.
为了确定改善长期移植物存活率的潜在治疗靶点,已经在肾移植(post-KTx)后早期研究了各种生物标志物。前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9(PCSK9)是一种在心血管疾病中引起关注的生物标志物,但它在 post-KTx 后的作用仍有待确定。
我们前瞻性地评估了 73 名接受肾移植的血液透析患者在 3 个时间点(移植前(第 0 天)和移植后 1 个月和 6 个月)的 PCSK9、白细胞介素(IL)-6、白细胞和 C 反应蛋白的水平。所有数据还根据供体类型(活体或已故)进行了分析,并与移植等候名单上的血液透析患者进行了比较。
在第 0 天,计划接受移植的患者与仍在接受血液透析的患者之间,白细胞、CRP、IL-6 和 PCSK9 水平没有差异。在接受移植的患者中,白细胞、CRP 和 IL-6 水平在 post-KTx 早期显著降低[logIL-6 第 0 天:0.68(0.33,0.85)vs. 1 个月:0.57(0.37,0.75)vs. 6 个月:0.50(0.32,0.69)pg/ml,p=0.01],而 PCSK9 水平显著升高(第 0 天:199.8±63.0 vs. 1 个月:276.2±79.4 vs. 6 个月:245.9±62.5 ng/ml,p<0.001)。相比之下,在随访的血液透析患者中,白细胞、CRP、IL-6 和 PCSK9 水平没有变化(所有 p=NS)。在活体供体和已故供体受者之间,分析显示两组 CRP 降低,PCSK9 水平升高(所有 p<0.05),而 IL-6 水平在活体供体受者中降低,在已故供体受者中升高 post-KTx 后 1 个月。PCSK9 水平与肾功能、延迟移植物功能、排斥反应或炎症生物标志物无关。
在活体和已故供体受者中,PCSK9 水平在 post-KTx 后升高,与肾功能和炎症生物标志物无关。