Matsuo Mitsunori, Taguchi Kensei, Yokota Yunosuke, Fukami Kei, Igawa Tsukasa
Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
PLoS One. 2025 Apr 15;20(4):e0321769. doi: 10.1371/journal.pone.0321769. eCollection 2025.
Robot-assisted laparoscopic partial nephrectomy (RAPN) is a safe and effective option for renal cell carcinoma (RCC). However, clamping of renal artery during RAPN sometimes causes ischemic reperfusion (IR) injury (IRI), which affects renal function at some later time. In the present study, we inserted catheters into the bilateral ureters from before RAPN until 24 hours after and analyzed urine biomarkers of renal injury excreted from both resected and contralateral kidneys to determine and investigated which biomarkers predict the future decline in renal function in patients with RCC and rodent IR model. Twenty-three patients diagnosed with RCC (66.4 ± 10.8 years old, eGFR: 73.6 ± 15.3 mL/min/1.73m2) were enrolled and ureteral catheters were inserted in both ureters. Urinary neutrophil gelatinase-associated lipocalin (NGAL), beta-2-microglobulin (β₂MG), N-acetyl-β-D-glucosaminidase were measured at several time points. Gene expression of injury markers in contralateral kidneys were analyzed in unilateral IR rodents. All the urinary markers were elevated 30 minutes after the clamping and sustained high until 24 hours in resected kidneys. Meanwhile, urinary NGAL and β2MG excreted from contralateral kidneys increased at 6 and 24 hours after the clamping. Warm ischemic time, estimated blood loss, and excised kidney weight were not associated with renal dysfunction; however, only contralateral urinary β2MG at 6 hours was correlated. Ngal and Il-6 mRNA in contralateral kidneys were upregulated in unilateral IR rodents. RAPN-related IRI induces contralateral kidney injury. Contralateral urinary β2MG can become a potent biomarker to predict the onset of kidney injury after RAPN.
机器人辅助腹腔镜肾部分切除术(RAPN)是治疗肾细胞癌(RCC)的一种安全有效的方法。然而,RAPN过程中肾动脉夹闭有时会导致缺血再灌注(IR)损伤(IRI),这会在之后的某个时间影响肾功能。在本研究中,我们在RAPN术前至术后24小时期间将导管插入双侧输尿管,并分析切除侧和对侧肾脏排出的肾损伤尿液生物标志物,以确定并研究哪些生物标志物可预测RCC患者和啮齿动物IR模型未来的肾功能下降。纳入了23例诊断为RCC的患者(年龄66.4±10.8岁,估算肾小球滤过率:73.6±15.3 mL/min/1.73m2),并在双侧输尿管插入输尿管导管。在多个时间点测量尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、β2微球蛋白(β₂MG)、N-乙酰-β-D-氨基葡萄糖苷酶。在单侧IR啮齿动物中分析对侧肾脏损伤标志物的基因表达。所有尿液标志物在夹闭后30分钟升高,并在切除侧肾脏中持续高水平直至24小时。同时,夹闭后6小时和24小时,对侧肾脏排出的尿NGAL和β2MG增加。热缺血时间、估计失血量和切除肾脏重量与肾功能障碍无关;然而,仅夹闭后6小时对侧尿β2MG与之相关。单侧IR啮齿动物对侧肾脏中的Ngal和Il-6 mRNA上调。RAPN相关的IRI会导致对侧肾脏损伤。对侧尿β2MG可成为预测RAPN后肾损伤发生的有效生物标志物。