Arimilli Bhargav, On Tyler A, Srirama Vaishnavi S, Yang Ye, Asampille Gitanjali, Brender Jeffrey R, Krishna Murali C, Hseuh Jessica Y, Chegu Viraj P, Kozel Zachary, Gurram Sandeep, Ball Mark W, Linehan William Marston, Crooks Daniel R
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Clinical Cancer Metabolism Facility, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Metabolites. 2025 Jul 8;15(7):462. doi: 10.3390/metabo15070462.
: Thousands of nephrectomies are performed annually in the United States, but the short-term metabolic effects of surgically induced renal ischemia remain unclear. The conventional metabolic markers used to characterize post-surgical renal function, such as creatinine and GFR, are measured in the serum but do not provide metabolic information about the renal parenchyma itself. We aimed to characterize the immediate metabolic effects of surgical ischemia on renal parenchyma within a temporal framework. : Timed renal parenchyma biopsies were collected from eight patients undergoing nephrectomy for renal cell carcinoma both prior to and after ligation of the renal hilum. These samples were ground, extracted, and analyzed using nuclear magnetic resonance (NMR) spectroscopy to measure changes in lactate, succinate, glucose, alanine, and glycine levels. : Due to experimental limitations, we were only able to draw limited conclusions from three patients. Of the five remaining patients, all had significant increases in lactate and succinate levels as a function of time, though the degree to which these increases occurred varied between each patient. Glucose levels generally decreased in the renal parenchyma but did not necessarily correlate with lactate production, assuming all glucose underwent fermentation to lactate in a hypoxic environment. Alanine and glycine levels did not change in a predictable pattern across patients. : There are significant changes in lactate, glucose and succinate levels within minutes of the onset of renal ischemia in human patients. The degree of change in the metabolites analyzed varied significantly between patients. The length of surgical ischemia must be considered during surgical procurement of tumor specimens for metabolomic analysis.
在美国，每年要进行数千例肾切除术，但手术诱导的肾缺血的短期代谢影响仍不清楚。用于表征术后肾功能的传统代谢标志物，如肌酐和肾小球滤过率（GFR），是在血清中测量的，但不能提供关于肾实质本身的代谢信息。我们旨在在一个时间框架内表征手术缺血对肾实质的即时代谢影响。
从八名因肾细胞癌接受肾切除术的患者在肾蒂结扎前后采集定时肾实质活检样本。将这些样本研磨、提取，并使用核磁共振（NMR）光谱进行分析，以测量乳酸、琥珀酸、葡萄糖、丙氨酸和甘氨酸水平的变化。
由于实验限制，我们仅能从三名患者中得出有限的结论。在其余五名患者中，所有患者的乳酸和琥珀酸水平均随时间显著升高，尽管这些升高的程度在每个患者之间有所不同。肾实质中的葡萄糖水平通常会下降，但不一定与乳酸生成相关，假设在缺氧环境中所有葡萄糖都发酵生成乳酸。不同患者的丙氨酸和甘氨酸水平没有呈现出可预测的变化模式。
在人类患者肾缺血开始后的几分钟内，乳酸、葡萄糖和琥珀酸水平会发生显著变化。所分析的代谢物的变化程度在患者之间差异显著。在为代谢组学分析进行肿瘤标本手术采集时，必须考虑手术缺血的时长。
