Effect Of ACEI/ARB On Contrast-Induced Acute Kidney Injury In Patients With Contrast Media Exposure

OBJECTIVES:To investigate the effect of ACEI/ARB drugs on contrast-associated acute kidney injury(CI-AKI)after exposure to contrast agents,with a view to demonstrating the discontinuation or non-discontinuation of ACEI/ARB drugs before contrast contact;and to investigate the molecular mechanism of ACEI/ARB drugs on contrast nephropathy by constructing a mouse model of contrast nephropathy.METHODS:A prospective,multicenter,randomized controlled study was conducted.1300 patients,who were included from Shenzhen People’s Hospital and Guangdong Provincial People’s Hospital from October 2017 to December 2019 and were regularly treated with ACEI/ARB for more than 1 week and agreed to undergo elective coronary angiography or coronary enhancement CTA,were included.There were randomized 1:1 using an envelope randomization method into two groups,i.e.the ACEI/ARB discontinuation group(24 hours before and 48 hours after exposure to contrast agents to investigate ACEI/ARB drugs)and the non-stop ACEI/ARB group.Renal function was measured before exposure to the contrast medium,at 48 hours and at 48 hours after.In the basic study,mouse models of contrast nephropathy were constructed using tail vein injection of indomethacin and iopromide.The mice were divided into control and experimental groups by the presence or absence of ACEI/ARB drug effects.In the control group and the experimental group,peripheral blood plasma was collected on day 7 by removing the eyeballs and the expression of blood creatinine and blood urea nitrogen was measured.The expression of Caspase-3 and Bcl-2 was measured by Western Blot.Finally,the effect of ACEI/ARB class on the apoptosis of HK2 cells was investigated by in vitro cytology.RESULTS:A total of 1300 patients exposed to contrast examination were included in this study.Baseline characteristics of patients in the ACEI/ARB and no ACEI/ARB groups were compared,including mean age(57.1±13.9 years vs.57.1±12.7 years,P=0.978),hypertension(580,89.23%vs.594,91.38%,P=0.874),baseline creatinine levels(96.91±41.85 vs.97.27±45.93,P=0.883)did not differ significantly between groups.Similarly,there were no significant between-group differences in the demographic characteristics,laboratory parameters,clinical presentation,type of angiography,medication,contrast dosage or daily fluid intake.the incidence of CI-AKI(primary endpoint)was 2.92%vs.2.62%in the ACEI/ARB and no-ACEI/ARB groups,respectively(P=0.866),while the incidence of in-hospital,the incidence of MACEs and the renal replacement therapy was 8.62%vs.8.92%(P=0.837)and 0%vs.0%,respectively.There were no significant between-group differences in MACEs(19.54%vs.18.92%,P=0.872)or renal replacement therapy(0.31%vs.0.15%,P=0.795)at the one-year follow-up.Subgroup analysis revealed that among patients with eGFR<45 mL/min,the incidence of CI-AKI was significantly higher in the ACEI/ARB group[17.95%(14/78)]than in the no-ACEI/ARB group[6.02%(5/83),P=0.029].However,in patients with eGFR>45 mL/min,the incidence of CI-AKI was[0.87%(5/572)vs.2.12%(12/567),P=0.094],respectively,with no significant difference.In the basic study,no statistically significant differences were found in renal injury,abnormal renal function and Bcl-2 and Cleaved-Caspase-3 expression in renal tissue in the ARB/ACEI group compared to the contrast agent alone group;also apoptosis of HK2 cells and Bcl2 and Cleaved-Caspase-3 expression in HK2 cells in the ARB/ACEI group compared to the iohexol alone group were found.-3 expression were not statistically different.CONCLUSIONS:ACEI/ARBs should be avoided prior to contrast exposure in patients with eGFR<45 mL/min.asic studies have further demonstrated that ACEI/ARBs do not exacerbate kidney tissue damage and HK2 cell apoptosis in mice with contrast nephropathy.