1 ITUN, Department of Nephrology and Immunology, INSERM UMR S-1064, Nantes, France. 2 SPHERE (Biostatistics, Pharmacoepidemiology and Human Sciences Research) Laboratory-EA 4275, LabEx Transplantex, Nantes University, Nantes, France. 3 Department of Pathology, CHU de Nantes, Nantes, France. 4 Address correspondence to: Fadi Fakhouri, M.D., Ph.D., INSERM U643, ITUN, Université de Nantes and Nephrology Department CHU de Nantes, Nantes, France.
Transplantation. 2013 Oct 27;96(8):739-44. doi: 10.1097/TP.0b013e31829f4772.
Ischemia-reperfusion induces tubular and endothelial damage in the renal graft and leads to delayed graft function (DGF) and to an early loss of peritubular capillaries (PTC). Few, if any, clinical studies have assessed the impact of proangiogenic and antiangiogenic factors on endothelial repair during renal transplantation (RT)-related ischemia-reperfusion.
We prospectively assessed the kinetics of the antiangiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) in 136 consecutive RT patients and analyzed sFlt-1 impact on DGF and PTC loss.
sFlt-1 plasma levels increased by twofold to threefold throughout the first week after RT. This increase was more marked in recipients of grafts from deceased donors compared with living donors. Patients with DGF had higher sFlt-1 levels at all time points during the first 7 days after RT and a higher peak sFlt-1 compared with those without DGF. In multivariate analysis, a peak plasma sFlt-1 of 250 pg/mL or higher was associated with 2.5-fold increase in the risk of DGF (P=0.04). Similarly, patients with a peak plasma sFlt-1 of 250 pg/mL or higher had a more pronounced early decrease in PTC compared with those with a peak sFlt-1 less than 250 pg/mL.
sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.
缺血再灌注会导致移植肾的肾小管和内皮损伤，引发延迟性肾功能恢复（DGF）和肾小管周毛细血管（PTC）早期丢失。目前很少有临床研究评估促血管生成和抗血管生成因子对肾移植相关缺血再灌注期间内皮修复的影响。
我们前瞻性评估了 136 例连续肾移植患者的抗血管生成因子可溶性 Fms 样酪氨酸激酶-1（sFlt-1）的动力学，并分析了 sFlt-1 对 DGF 和 PTC 丢失的影响。
sFlt-1 血浆水平在肾移植后第一周内增加了两倍至三倍。与活体供者相比，来自已故供者的受者 sFlt-1 增加更为明显。所有 DGF 患者在肾移植后第 1 天至第 7 天的所有时间点 sFlt-1 水平均较高，且峰值 sFlt-1 高于无 DGF 患者。多变量分析显示，血浆 sFlt-1 峰值达到或高于 250pg/ml 时，DGF 的风险增加 2.5 倍（P=0.04）。同样，血浆 sFlt-1 峰值达到或高于 250pg/ml 的患者与峰值 sFlt-1 低于 250pg/ml 的患者相比，PTC 早期丢失更为明显。
sFlt-1 是 DGF 和 PTC 丢失的一个新的非免疫独立危险因素。其抑制可能有助于改善肾移植的结果。
