Mansour S G, Puthumana J, Reese P P, Hall I E, Doshi M D, Weng F L, Schröppel B, Thiessen-Philbrook H, Bimali M, Parikh C R
Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, CT.
Section of Nephrology, Yale University School of Medicine, New Haven, CT.
Kidney Int Rep. 2017 Jul;2(4):749-758. doi: 10.1016/j.ekir.2017.03.007. Epub 2017 Mar 31.
Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes.
We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR.
AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR.
Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.
目前用于预测在已故供体肾脏获取过程中受者同种异体移植功能的方法并不精确。了解单核细胞趋化蛋白-1(MCP-1)的潜在肾脏修复作用,一种参与损伤后巨噬细胞募集的细胞因子,可能有助于预测移植结果。
我们对多中心前瞻性已故供体研究队列进行了一项子研究,该队列评估了2010年5月至2013年12月期间来自五个器官获取组织的已故肾脏供体。我们测量了肾切除时收集的供体样本中的尿MCP-1(uMCP-1)浓度,以确定其与供体急性肾损伤(AKI)、受者移植肾功能延迟恢复(DGF)、6个月估计肾小球滤过率(eGFR)和移植失败的相关性。我们还评估了灌注肾脏的灌注液MCP-1浓度与DGF和6个月eGFR的相关性。
111名(9%)供体发生了AKI。与未发生AKI的供体相比,发生AKI的供体的uMCP-1浓度中位数(四分位间距)更高(1.35[0.41 - 3.93]ng/ml对0.32[0.11 - 0.80]ng/ml,p<0.001)。756名(31%)受者发生了DGF,但uMCP-1与DGF无独立相关性。在未发生DGF的受者中,供体uMCP-1浓度较高与6个月时较高的eGFR独立相关[每uMCP1翻倍,eGFR增加0.77(0.10,1.45)ml/min/1.73m²]。然而,在约2年的中位随访期内,uMCP-1与移植失败之间无独立相关性。最后,灌注液MCP-1浓度在泵灌注期间显著增加,但与DGF或6个月eGFR无关。
在未发生DGF的受者中,供体uMCP-1浓度与受者6个月时较高的eGFR有适度关联。然而,结果表明,鉴于供体uMCP-1与移植失败无关联,其临床应用价值极小。