Faure Jean Pierre, Petit Isabelle, Zhang Keqiang, Dutheil Delphine, Doucet Carole, Favreau Frédéric, Eugène Michel, Goujon Jean Michel, Tillement Jean Paul, Mauco Gérard, Vandewalle Alain, Hauet Thierry
Institut National de la Santéet de la Recherche Médicale (INSERM) ERM 324, rue de La Milétrie, 86000 Poitiers, France.
Am J Transplant. 2004 Apr;4(4):495-504. doi: 10.1111/j.1600-6143.2004.00365.x.
Ischemia-reperfusion injury (IRI) represents an allo-independent risk factor which favors chronic allograft nephropathy (CAN). Here we analyzed the influence of preservation solutions on the function of autotransplanted pig kidneys over 1-16 weeks after surgery. Kidneys were cold-flushed and cold-stored for 24 or 48 h either in University of Wisconsin (UW), modified-UW Hôpital Edouard Herriot, polyethylene glycol 20 kDa (PEG)-supplemented preservation solutions with low K+ (ECPEG) or high K+ (ICPEG) content. Animals autotransplanted with kidneys cold-stored for 24 h in ECPEG exhibited the greatest levels of creatinine clearance (Ccr: 161 +/- 12 mL/min, n=10) and the lowest levels of proteinuria (0.5 +/- 0.03 mg/mL) 16 weeks after surgery as compared with pigs autotransplanted with kidneys cold-stored in the other solutions tested (Ccr ranging from 80 and 140 mL/min). Similar differences, but with lower Ccr levels, were achieved after a prolonged period of cold-storage(48 h). ECPEG better preserved the kidneys from monocytes/macrophages and CD4+ T cells infiltrations, VCAM-1 and MHC class II overexpressions and occurrence of renal interstitial fibrosis (2%) as compared with the other preservation solutions (5%-20%). Adding the anti-ischemic drug trimetazidine (TMZ) to the preservation solutions, particularly ECPEG, further improved the quality of the week-16 post-transplanted kidneys (Ccr: 182 +/- 12 mL/min, n=10). These findings demonstrated that adding PEG to extracellular-like (with low K+ content) preservation solutions in combination with TMZ significantly improved the long-term outcome of kidney grafts in this model of autotransplanted pig kidney.
缺血再灌注损伤（IRI）是一种与同种异体无关的危险因素，易引发慢性移植肾肾病（CAN）。在此，我们分析了保存液对自体移植猪肾术后1至16周功能的影响。肾脏在威斯康星大学（UW）、改良UW爱德华·赫里奥特医院、添加低K⁺（ECPEG）或高K⁺（ICPEG）含量的聚乙二醇20 kDa（PEG）的保存液中进行冷灌注和冷保存24或48小时。与用其他测试保存液冷保存肾脏的自体移植猪相比，在ECPEG中冷保存24小时的肾脏进行自体移植的动物在术后16周时肌酐清除率（Ccr：161±12 mL/min，n = 10）最高，蛋白尿水平（0.5±0.03 mg/mL）最低（其他保存液组的Ccr在80至140 mL/min之间）。长时间冷保存（48小时）后也出现了类似差异，但Ccr水平较低。与其他保存液（5%-20%）相比，ECPEG能更好地保护肾脏免受单核细胞/巨噬细胞和CD4⁺T细胞浸润、VCAM-1和MHC II类分子过度表达以及肾间质纤维化（2%）的影响。在保存液中添加抗缺血药物曲美他嗪（TMZ），特别是添加到ECPEG中，能进一步改善移植后16周肾脏的质量（Ccr：182±12 mL/min，n = 10）。这些发现表明，在低K⁺含量的类似细胞外保存液中添加PEG并联合TMZ可显著改善该自体移植猪肾模型中肾移植的长期效果。
