Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats

作者：Togashi Yuko; Sakaguchi Yuka; Miyamoto Mari; Miyamoto Yohei^*

来源：Experimental and Toxicologic Pathology, 2012, 64(7-8): 797-805.

DOI：10.1016/j.etp.2011.01.018

• Acute kidney injury (AKI)
• Biomarker
• Cisplatin (CDDP)
• Cystatin C
• Immunohistochemistry

Cystatin C. a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the urinary and plasma levels of cystatin C and how useful they are for the early detection of acute kidney injury (AKI) in CDDP-treated rats in comparison with other biomarkers (beta 2-microglobulin, calbindin, clusterin, EGF, GST-alpha, GST-mu KIM-1, NGAL, osteopontin, TIMP-1, and VEGF). The urinary levels of cystatin C, GST-alpha, KIM-1, and EGF changed prior to proximal tubule damage and increases in plasma urea nitrogen and creatinine levels, suggesting their usefulness for predicting AKI. On the other hand, the plasma cystatin C level hardly changed. We also investigated the localization of cystatin C in the kidney according to the progression of renal damage. Cystatin C was predominantly localized in the proximal tubule of the cortex, and its immunohistochemical expression was not affected by CDDP treatment. In addition, cystatin C was observed in the lumen of the renal tubule in the cortex, cortico-medullary junction, and medulla during the progression of renal damage, although its immunoreactive area ratio was very low.
In conclusion, urinary cystatin C measurements can detect CDDP-induced AKI as early as KIM-1. GST-alpha, and EGF in rats, although the change ratio of the cystatin C was smaller than others. Immunohistochemical cystatin C expression in the proximal tubule of the kidney was hardly changed by the CDDP treatment, but it was newly observed in the renal tubule lumen after CDDP treatment.

• 出版日期2012-11