Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Evergreen Health, Urology & Urogynecology, Kirkland, Washington, USA.
J Endourol. 2024 Jul;38(7):701-706. doi: 10.1089/end.2023.0289. Epub 2024 Jun 7.
Renoprotection from reperfusion injury appears to be conferred by HIF-2a activation, which can be stimulated by exogenous acetate administration. The study objective was to assess whether administration of acetate in a porcine model can mitigate kidney injury related to ischemia-reperfusion after renal hilar occlusion. A porcine single-kidney model was created by performing a laparoscopic nephrectomy followed by animal recovery. After 2 days, the animals underwent laparoscopic hilar dissection. Block randomization was used to assign pigs into one of four experimental groups. One treatment block of pigs received 150 mEq of sodium acetate intravenously during 90 minutes of en bloc occlusion of the renal hilum (herein noted as "cross-clamping"). Another block received 0.75 g/kg of oral sodium acetate for 3 days prior to cross-clamping. A third block received no acetate and underwent hilar dissection without cross-clamping (negative control). The final block received no acetate and underwent cross-clamping (positive control). Serum creatinine was used to estimate renal function post-nephrectomy. A total of 16 animals (4 pigs in each group) completed the study protocol. Median pig weight was 34.6 kg. One pig receiving IV acetate was excluded from the final analysis because of unrecoverable renal failure after cross-clamping. There was a significantly lower mean serum creatinine for the IV acetate group compared with the positive control group 72 hours after cross-clamping ( = 0.012). The same effect was not observed for the pigs receiving oral acetate. By day 7, renal function had recovered without significant difference in all groups. We observed that the administration of intravenous acetate conferred a significant renoprotective benefit in our single kidney ischemia-reperfusion porcine model 72 hours after hilar occlusion. This work is hypothesis-generating, and further work in human subjects undergoing renal hilar occlusion during partial nephrectomy is warranted.
肾保护作用似乎来自于 HIF-2a 的激活，而外源性醋酸盐的给予可以刺激其激活。本研究的目的是评估在猪模型中给予醋酸盐是否可以减轻肾门阻断后与缺血再灌注相关的肾损伤。通过腹腔镜肾切除术和动物恢复后建立猪单肾模型。两天后，动物进行腹腔镜肾门解剖。采用区块随机化将猪分配到四个实验组中的一个。一组治疗的猪在肾门整块阻断的 90 分钟内接受 150 mEq 的静脉内醋酸钠（在此称为“阻断夹闭”）。另一组在阻断夹闭前 3 天接受 0.75 g/kg 的口服醋酸钠。第三组不接受醋酸盐，并且在不进行阻断夹闭的情况下进行肾门解剖（阴性对照）。最后一组不接受醋酸盐并且进行阻断夹闭（阳性对照）。手术后通过血清肌酐估计肾功能。共有 16 只动物（每组 4 只）完成了研究方案。中位数猪体重为 34.6kg。由于阻断夹闭后发生不可逆转的肾衰竭，接受 IV 醋酸盐的一只猪被排除在最终分析之外。阻断夹闭后 72 小时，IV 醋酸盐组的平均血清肌酐明显低于阳性对照组（ = 0.012）。接受口服醋酸盐的猪则没有观察到相同的效果。到第 7 天，所有组的肾功能均已恢复，无明显差异。我们观察到，在我们的单个肾缺血再灌注猪模型中，肾门阻断后 72 小时给予静脉内醋酸盐可显著减轻肾损伤。这项工作是假设生成性的，需要进一步在部分肾切除术期间进行肾门阻断的人类受试者中开展工作。
