Department of Surgery, Maastricht University Medical Center, The Netherlands.
Ann Surg. 2011 Mar;253(3):598-604. doi: 10.1097/SLA.0b013e31820d9ae9.
To provide an integrated insight into the kinetics of tubular injury, inflammation, and oxidative stress after human kidney transplantation.
Tissue injury due to ischemia and reperfusion is an inevitable consequence of kidney transplantation. Tubular epithelial injury, inflammation, and oxidative stress play major roles in the pathophysiology of acute kidney injury in small animals, but it remains to be established whether this paradigm holds true for human kidney transplantation.
Markers of tubular injury, inflammation, and oxidative stress were compared between recipients of kidneys from donors after cardiac death (DCD; N = 8) with prolonged ischemia and recipients of living donor kidneys with minimal ischemia (N = 8).
In the early postoperative period, creatinine clearance and tubular sodium reabsorption were profoundly reduced in DCD kidneys, coinciding with significantly increased urinary concentrations of tubular injury markers (neutrophil gelatinase-associated lipocalin, N-acetyl-β--glucosaminidase, and cystatin C) and an 18-fold increase in renal production of cytokeratin-18, indicating extensive necrotic cell death. Tubular injury in DCD kidneys was followed by greater systemic inflammatory activity and oxidative stress in the postoperative period (measured with 17-plex cytokine arrays and as plasma F2-isoprostanes, respectively). In contrast, no evidence of oxidative damage to either of the 2 kidney types was found in the early reperfusion period.
These findings establish the relevance of observations in animal models for human kidney transplantation and form the basis for development of novel therapies to improve early graft function and expand the use of donor kidneys with prolonged ischemia.
全面了解人类肾移植后肾小管损伤、炎症和氧化应激的动力学。
缺血再灌注引起的组织损伤是肾移植不可避免的后果。在小动物的急性肾损伤病理生理学中，肾小管上皮损伤、炎症和氧化应激起着主要作用，但这一范式是否适用于人类肾移植仍有待确定。
比较心脏死亡供体（DCD；N=8）肾移植中存在长时间缺血和最小缺血的活体供体肾移植受者的肾小管损伤、炎症和氧化应激标志物。
在术后早期，DCD 肾脏的肌酐清除率和肾小管钠重吸收明显降低，同时尿中肾小管损伤标志物（中性粒细胞明胶酶相关脂质运载蛋白、N-乙酰-β-氨基葡萄糖苷酶和胱抑素 C）浓度显著升高，细胞角蛋白-18 的肾生成增加 18 倍，表明广泛的坏死性细胞死亡。DCD 肾脏的肾小管损伤随后在术后期间导致更大的全身炎症活性和氧化应激（分别用 17 重细胞因子阵列和血浆 F2-异前列腺素测量）。相比之下，在早期再灌注期间，两种类型的肾脏均未发现氧化损伤的证据。
这些发现确立了动物模型观察结果在人类肾移植中的相关性，并为开发新的治疗方法奠定了基础，以改善早期移植物功能并扩大使用长时间缺血的供体肾脏。
