Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human

Abstract

Background: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. Methods: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. Results: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. Conclusions: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.