Quantitative Analysis of Microperfusion in Contrast-Induced Nephropathy Using Contrast-Enhanced Ultrasound: An Animal Study

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MeSH: Acute Kidney Injury / diagnosis ; Acute Kidney Injury / etiology* ; Animals ; Disease Models, Animal ; Interleukin-18 / genetics ; Interleukin-18 / metabolism ; Kidney / metabolism ; Kidney / pathology ; Kidney Function Tests ; Lipocalin-2 / genetics ; Lipocalin-2 / metabolism ; Male ; Phospholipids / adverse effects* ; Proto-Oncogene Proteins c-bcl-2 / genetics ; Proto-Oncogene Proteins c-bcl-2 / metabolism ; Rats ; Rats, Sprague-Dawley ; Sulfur Hexafluoride / adverse effects* ; Ultrasonography* ; Up-Regulation ; bcl-2-Associated X Protein / genetics ; bcl-2-Associated X Protein / metabolism

Keywords: Acute kidney injury ; Animal experimentation ; Contrast media ; Contrast-enhanced ultrasonography ; Perfusion

Abstract: Objective: To investigate imaging biomarkers of microperfusion in contrast-induced nephropathy (CIN) using contrast-enhanced ultrasound (CEUS).

Materials and methods: The CIN model was fabricated by administering indomethacin (10 mg/kg), L-NAME (15 mg/kg), and iopamidol (10 mL/kg) to Sprague-Dawley rats. After 24 hours, CEUS was performed on CIN (n = 6) and control (n = 6) rats with sulphur hexafluoride microbubbles (SonoVue). From time-intensity curves obtained from the kidney arriving time (AT), acceleration time (AC), time to peak (TTP), and peak enhancement (PE) were measured and compared between the groups. After CEUS, the rats were sacrificed, and cell apoptosis markers were evaluated to confirm the development of CIN.

Results: Among CEUS parameters, AT (7.8 ± 1.6 vs. 4.2 ± 0.5 s, p = 0.002), AC (4.7 ± 1.4 vs. 2.0 ± 0.4 s, p = 0.002), and TTP (12.5 ± 2.9 vs. 6.2 ± 0.6 s, p = 0.002) were significantly prolonged in the CIN group compared to controls. PE was significantly higher in the control group than in the CIN group (17.1 ± 1.9 vs. 12.2 ± 2.0 dB, p = 0.004). In kidney tissue, mRNA and protein levels of the apoptotic makers were significantly higher in the CIN group than in the control group (p = 0.003 and p = 0.002).

Conclusion: CEUS parameters can be used as imaging biomarkers for microperfusion in CIN. In rats with CIN, AT, AC, and TTP were significantly prolonged, while PE was significantly lower compared to controls.