Efficacy Of Alprostadil In Preventing Contrast Induced Nephropathy In Elderly Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Background:At present,the role of alprostadil in the prevention of contrast induced nephropathy(CIN)remains controversial.The purpose of this study was to investigate the preventive effects,the possible mechanism and the safety of short-term alprostadil on the CIN in elderly patients with acute coronary syndrome(ACS)undergoing percutaneous coronary intervention(PCI),and further explored the prophylactic efficacy of alprostadil in various risk stratified patients.Methods:The study prospectively enrolled 480 elderly patients with ACS undergoing PCI from Tianjin Chest Hospital,Tianjin First Central Hospital,Tianjin Fourth Central Hospital and TEDA International Cardiovascular Hospital from January 2015 to December 2016,who were randomly divided into the control group and the alprostadil control.The control group(n=240)was given only hydration therapy and the alprostadil group(n=240)received intravenous alprostadil administration of 20ug/day(diluted with 100 ml normal saline)from 0.5~1h before to 3 days after operation on the basis of hydration.The study recorded serum creatinine(SCr)and estimated glomerular filtration rate(eGFR)pre-and 48~72h post-operation,blood urea nitrogen(BUN),serum uric acid(SUA),high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hcy)pre-and 48h post-operation,Cystin C(CysC)pre-and 24h post-operation.The primary endpoint of the study was the incidence of CIN,defined as an increase in SCr concentration?44.2 umol/l or?25%above baseline within 48~72h after exposure of contrast media.Furthermore,CIN was classified into three grades as follows:grade 0-no CIN;grade 1-increase in SCr?25%but?44.2umol/L;grade 2-increase in SCr?44.2 umol/L.Other endpoint events included:(1)the incidence of CIN defined by other diagnostic criteria;(2)the efficacy of alprostadil on prevention of CIN in prespecified subgroups;(3)a composite of adverse events in hospitalization.Results:1.The baseline characteristics of two groups were similar,without statistically significant difference(P>0.05).2.(1)The primary endpoint of CIN occurred in 43 patients(8.96%):15(6.25%)in the alprostadil group and 28(11.67%)in the control group,with statistically significant differences(P=0.038).(2)A multivariate logistic regression model was established and the results revealed that alprostadil was a protective factor for CIN and contrast volume,diabetes mellitus and acute myocardial infarction significantly increased the risk of CIN.(3)In all the prespecified subgroups,a significant reduction of CIN was observed in patients with diabetes mellitus,contrast volume?140ml and in those received low-osmolar contrast media.On the contrary,the effect of alprostadil was attenuated in the subgroups with acute myocardial infarction,baseline LVEF?45%and baseline eGFR?60 ml/min/1.73 m~2.3.(1)Laboratory results comparisons within group:the postoperative SCr,CysC?hs-CRP levels in the two groups and the postoperative Hcy levels in the control group were significantly higher than preoperative levels(P<0.05).However,the postoperative Hcy levels in the alprostadil was not significantly higher than preoperative levels(P>0.05).The postoperative eGFR,BUN,and SUA levels in both groups were significantly lower than preoperative levels(P<0.05).(2).Laboratory results comparisons between the two groups:There were no significant differences in the postoperative 48h,72h levels of SCr and eGFR between the two groups(P>0.05).There were also no significantly differences in the postoperative48h levels of BUN and SUA between the two groups(P>0.05),but the absolute changes of SUA(?SUA)in the alprostadil group were significantly higher than those in the control group(P<0.05),while?BUN was not observed significant difference(P>0.05).The postoperative 24h levels of CysC and the postoperative 48h levels of hs-CRP and Hcy in the alprostadil group were significantly lower than those in the control group(P<0.05).4.A CyC increase of?10%after contrast media administration was the optimum cutoff value for early diagnosis of CIN and a CyC increase of 10%had a97.67%sensitivity and a 81.92%specificity for predicting SCr-based CIN.Conclusions:1.Perioperative administration of alprostadil could reduce the incidence of CIN in patients with ACS undergoing PCI,and alprostadil was more beneficial to patients with diabetes mellitus or receiving high-dose contrast media.2.Alprostadil could reduce the level of SUA,hs-CRP and Hcy,which were involved in the inflammation and oxidative stress reaction of CIN,meaning that alprostadil may prevent CIN through the inhibition of inflammatory and oxidative stress.3.An increase of?10%in CysC levels within 24h after contrast agent exposure can be used for the early diagnosis of CIN,which helps early recognition of renal function changes and perform early preventive intervention.