Weld Kyle J, Montiglio Claudio, Bush Anneke C, Dixon Patricia S, Schwertner Harvey A, Hensley Donna M, Cowart Jerry R, Cespedes R Duane
Departments of Urology and Clinical Research, Wilford Hall Medical Center, Lackland Air Force Base, Texas 78236, USA.
J Urol. 2008 Nov;180(5):2218-25. doi: 10.1016/j.juro.2008.07.017. Epub 2008 Sep 20.
We determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function.
Using a single kidney model 3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia, respectively. Microdialysis samples were collected before, during and after ischemia. Renal function assessments consisting of serum creatinine and GFR measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14 and 28. Kidneys exposed and not exposed to ischemia were collected for histological study.
Interstitial glucose and pyruvate concentrations decreased, while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered, while glycerol increased throughout warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. Functional data correlated with histological findings. The 120-minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD glycerol concentration of 167 +/- 24 micromol/l.
Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 micromol/l is associated with irreparable functional damage in this model.
我们通过检测肾皮质间质代谢变化来确定热缺血的最大肾耐受性，以识别不可修复肾功能的潜在实时标志物。
采用单肾模型，每组5头猪，共3组，分别接受120、150和180分钟的热缺血。在缺血前、缺血期间和缺血后采集微透析样本。在缺血前以及缺血后第1、5、9、14和28天进行包括血清肌酐和肾小球滤过率测量的肾功能评估。采集暴露于缺血和未暴露于缺血的肾脏进行组织学研究。
缺血期间，间质葡萄糖和丙酮酸浓度降低，而乳酸浓度升高至稳定水平。谷氨酸在缺血30分钟时达到峰值，随后逐渐下降，而甘油在整个热缺血期间持续增加。在缺血后第28天，120分钟缺血组的肾功能恢复到缺血前基线水平，但150分钟和180分钟缺血组未恢复到基线水平。功能数据与组织学结果相关。热缺血120分钟的最大肾耐受性与甘油平均浓度±标准差167±24微摩尔/升相关。
间质甘油是肾功能恶化的实时、肾单位特异性、微创标志物。在该模型中，猪肾暴露于缺血性损伤导致肾皮质间质甘油浓度高于167微摩尔/升与不可修复的功能损害相关。
