Ichikawa Daisuke, Kamijo-Ikemori Atsuko, Sugaya Takeshi, Ohata Keiichi, Hisamichi Mikako, Hoshino Seiko, Kimura Kenjiro, Shibagaki Yugo
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan.
Nephrology (Carlton). 2018 Apr;23(4):308-316. doi: 10.1111/nep.12998.
The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage.
Male human L-type fatty acid binding protein (L-FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion. The kidneys were analyzed 20 days after the last I/R.
Serum creatinine levels 20 days post-I/R were significantly higher in the 20 min I/R than in the 10 min I/R and control groups and were similar between the 10 min I/R and control groups. The degree of tubulointerstitial damage 20 days post-I/R was significantly more severe in the 20 min I/R than in the 10 min I/R and control groups, as well as in the 10 min I/R than in the control group. Urinary levels of human L-FABP, albumin, and kidney injury molecule-1 (KIM-1) 20 days post-I/R were significantly higher in the 20 min I/R than in the control group, whereas urinary L-FABP was significantly higher in the 10 min I/R than in the control group. Conversely, urinary neutrophil gelatinase-associated lipocalin levels did not significantly differ between the three groups. Finally, the urinary levels of human L-FABP, albumin, and KIM-1 levels 20 days post-I/R were significantly correlated with the degree of renal damage.
Urinary levels of human L-FABP, albumin and, KIM-1 may be useful for monitoring AKI-to-CKD transition in clinical practice.
本研究旨在阐明急性肾损伤（AKI）慢性期的肾小管标志物是否与慢性肾小管间质损伤相关。
雄性人L型脂肪酸结合蛋白（L-FABP）染色体转基因（Tg）小鼠通过肾蒂夹闭10分钟或20分钟进行缺血再灌注（I/R）损伤。在组织再灌注时进行对侧肾切除术。在最后一次I/R后20天对肾脏进行分析。
I/R后20天，20分钟I/R组的血清肌酐水平显著高于10分钟I/R组和对照组，而10分钟I/R组和对照组之间相似。I/R后20天，20分钟I/R组的肾小管间质损伤程度明显比10分钟I/R组和对照组严重，10分钟I/R组也比对照组严重。I/R后20天，20分钟I/R组的人L-FABP、白蛋白和肾损伤分子-1（KIM-1）尿水平显著高于对照组，而10分钟I/R组的尿L-FABP显著高于对照组。相反，三组之间的尿中性粒细胞明胶酶相关脂质运载蛋白水平无显著差异。最后，I/R后20天的人L-FABP、白蛋白和KIM-1尿水平与肾损伤程度显著相关。
人L-FABP、白蛋白和KIM-1的尿水平可能有助于临床实践中监测AKI向CKD的转变。
