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

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. (C) 2011 Elsevier GmbH. All rights reserved.