Wang Shujun, Pan Qingjun, Xu Chen, Li Jun-Jia, Tang Hao-Xuan, Zou Ting, Jing Kai-Peng, Ye Lin, Wu Hong-Luan, Liu Wei-Jing, Liu Hua-Feng
Cell Physiol Biochem. 2018;45(4):1700-1706. doi: 10.1159/000487776. Epub 2018 Feb 23.
BACKGROUND/AIMS: Massive proteinuria, a significant sign of nephrotic syndrome (NS), has the potential to injure tubular epithelial cells (TECs). Furosemide is widely used for the treatment of edema, a common manifestation of NS. However, whether furosemide treatment affects massive proteinuria-induced TEC injury in patients with NS is unknown.
The effect of furosemide on TEC damage was investigated in vitro. In addition, a clinical study was conducted to study whether the short-term treatment of nephrotic edema with furosemide could exacerbate TEC injury.
The proliferation of in vitro human kidney-2 (HK-2) cells exposed to massive urinary protein (8 mg/mL) significantly decreased (P<0.05), while the levels of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin (NGAL) in the supernatants significantly increased (P<0.05). Importantly, furosemide treatment did not further increase the expression of Kim-1 and NGAL in HK-2 cells upregulated by massive proteinuria. For the clinical study, 26 patients with NS, all prescribed the recommended dosage of prednisone (1 mg/kg/day), were randomly assigned to two groups. One group (n=13) received furosemide (60-120 mg/day, intravenously) for 1 week; the remaining participants (control group) did not receive furosemide or any other diuretics. The results showed that the 24-h urine volume in the furosemide-treated group was slightly, but not significantly, higher than that in the control group (P>0.05). In addition, serum levels of BUN, Scr, Cys C, and urinary Kim-1 and NGAL were not significantly different between the two groups (all P>0.05). Twenty-three patients underwent a renal biopsy. Of these, 22 patients exhibited vacuolar degeneration of the TECs; 8 patients showed brush border membrane shedding of the TECs; and 12 patients showed protein casts. However, there were no significant differences between the two groups (all P>0.05).
In summary, massive proteinuria induced the injury of TECs in patients with NS, and furosemide treatment did not aggravate this injury.
背景/目的：大量蛋白尿是肾病综合征（NS）的一个重要体征，有损伤肾小管上皮细胞（TECs）的潜在风险。呋塞米广泛用于治疗水肿，这是NS的常见表现。然而，呋塞米治疗是否会影响NS患者中大量蛋白尿诱导的TEC损伤尚不清楚。
在体外研究呋塞米对TEC损伤的影响。此外，开展了一项临床研究，以探讨用呋塞米短期治疗肾病性水肿是否会加重TEC损伤。
暴露于大量尿蛋白（8mg/mL）的体外培养人肾-2（HK-2）细胞的增殖显著降低（P<0.05），而上清液中肾损伤分子-1（Kim-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的水平显著升高（P<0.05）。重要的是，呋塞米治疗并未进一步增加因大量蛋白尿而上调的HK-2细胞中Kim-1和NGAL的表达。对于临床研究，26例NS患者均按推荐剂量服用泼尼松（1mg/kg/天），被随机分为两组。一组（n=13）静脉注射呋塞米（60-120mg/天），持续1周；其余参与者（对照组）未接受呋塞米或任何其他利尿剂治疗。结果显示，呋塞米治疗组的24小时尿量略高于对照组，但差异无统计学意义（P>0.05）。此外，两组之间的血清尿素氮、血清肌酐、胱抑素C水平以及尿Kim-1和NGAL水平均无显著差异（均P>0.05）。23例患者接受了肾活检。其中，22例患者出现TECs空泡变性；8例患者出现TECs刷状缘膜脱落；12例患者出现蛋白管型。然而，两组之间无显著差异（均P>0.05）。
总之，大量蛋白尿诱导了NS患者的TEC损伤，而呋塞米治疗并未加重这种损伤。
