肾病综合征中大量蛋白尿诱导的肾小管上皮细胞损伤不会因呋塞米而加重。

Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide.

作者信息

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

出版信息

Cell Physiol Biochem. 2018;45(4):1700-1706. doi: 10.1159/000487776. Epub 2018 Feb 23.

DOI:10.1159/000487776

PMID:29490294

Abstract

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.

METHODS

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.

RESULTS

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).

CONCLUSION

In summary, massive proteinuria induced the injury of TECs in patients with NS, and furosemide treatment did not aggravate this injury.

摘要

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。

方法

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。

结果

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）。