Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide
Massive Proteinuria-Induced Injury of Tubular Epithelial Cells in Nephrotic Syndrome is Not Exacerbated by Furosemide
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呋塞米不会加剧肾病综合征中大量蛋白尿引起的肾小管上皮细胞损伤
DOI：
10.1159/000487776
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发表时间：
2018-02
影响因子：
--
通讯作者：
Liu Hua feng
中科院分区：
文献类型：
--
作者：
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
背景/目的：大量蛋白尿是肾病综合征（NS）的一个重要体征，具有损伤肾小管上皮细胞（TEC）的潜力。呋塞米广泛用于治疗水肿，这是NS的常见表现。然而，速尿治疗是否影响NS患者大量蛋白尿诱导的TEC损伤尚不清楚。方法：观察速尿对离体TEC损伤的影响。此外，还进行了一项临床研究，以研究用呋塞米短期治疗肾病水肿是否会加重TEC损伤。结果如下：大量尿蛋白（8 mg/mL）可显著降低体外培养的人肾2（HK-2）细胞的增殖能力（P<0.05），而培养上清中的肾损伤分子1（Kim-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平显著升高（P<0.05）。重要的是，呋塞米治疗没有进一步增加大量蛋白尿上调的HK-2细胞中Kim-1和NGAL的表达。在临床研究中，26例NS患者，均接受推荐剂量的泼尼松（1 mg/kg/d），随机分为两组。一组（n=13）接受呋塞米（60-120 mg/天，静脉注射）1周;其余参与者（对照组）未接受呋塞米或任何其他利尿剂。结果显示，呋塞米治疗组24小时尿量较对照组略有增加，但无显著性差异（P>0.05）。此外，两组患者血清BUN、Scr、Cys C及尿Kim-1、NGAL水平差异均无统计学意义（均P>0.05）。23例患者接受了肾活检。其中，22例患者表现出空泡变性的TEC; 8例患者表现出刷状缘膜脱落的TEC;和12例患者表现出蛋白管型。但两组间差异无统计学意义（均P>0.05）。结论：NS患者大量蛋白尿可导致TEC损伤，速尿治疗不会加重这种损伤。
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.
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影响因子：
2.5
作者：
H. Nakahama;Y. Fukuhara;Y. Orita;A. Yamauchi;T. Takama;T. Kamada
通讯作者：
H. Nakahama;Y. Fukuhara;Y. Orita;A. Yamauchi;T. Takama;T. Kamada
影响因子：
4.5
作者：
Laura L. Boles Ponto;R. Schoenwald
通讯作者：
Laura L. Boles Ponto;R. Schoenwald
DOI：
10.1097/01.asn.0000067652.51441.21
发表时间：
2003-06-01
影响因子：
13.6
作者：
Bonventre, JV
通讯作者：
Bonventre, JV
影响因子：
19.6
作者：
KUNCIO, GS;NEILSON, EG;HAVERTY, T
通讯作者：
HAVERTY, T
DOI：
10.1590/s0100-879x2012007500093
发表时间：
2012-09
期刊：
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子：
--
作者：
Levi TM;Rocha MS;Almeida DN;Martins RT;Silva MG;Santana NC;Sanjuan IT;Cruz CM
通讯作者：
Cruz CM