The Value Of Monocyte To Lymphocyte Ratio And Cystatin C In Predicting Contrast-induced Nephropathy After Percutaneous Coronary Intervention

Background:With the development of modern imaging and interventional diagnosis and treatment technology,especially the widespread use of cardiac catheterization,the use of contrast media is becoming more frequent,so the contrast-induced nephropathy(CIN)caused by exposure to contrast media is becoming more common.CIN is the third leading cause of hospital-acquired acute kidney injury after renal hypoperfusion and the use of nephrotoxic drugs,which is associated with prolonged length of stay,increased health care costs and adverse clinical outcomes.The risk factors of CIN include advanced age,diabetes,chronic renal insufficiency,congestive heart failure,low blood volume,anemia,the amount of contrast media,the application of intra-aortic balloon pump,percutaneous coronary intervention(PCI),and so on.The incidence of CIN varies significantly among different population groups.Patients with coronary heart disease who underwent PCI often have multiple risk factors of CIN,so the incidence of CIN in these patients is high.The pathophysiology of CIN remains uncertain,several mechanisms have been put forward,including renal medullary hypoxia,the direct cytotoxicity of iodinated contrast on various renal cell types,the activation of oxidative stress and inflammation,and so on.Some data on the important role of inflammation for CIN exist.Monocyte to lymphocyte ratio(MLR)is a novel systemic inflammation marker that has been linked to the prognosis of tumors,the severity of the coronary artery lesion,coronary collateral circulation,and clinical outcomes.However,the relationship between MLR and CIN in patients who underwent PCI has not been investigated.Most CIN patients lack typical clinical symptoms,which are often characterized by non-oliguria acute renal injury.At present,CIN is mainly evaluated by monitoring SCr,which is susceptible to many factors and has been elevated at 24 hours after PCI.Cystatin C(Cys-C)is a non-glycosylated basic protein,which is expressed by almost all nucleated cells in human.The secretion of Cys-C is constant every day,which is not susceptible to age,diet and other factors.Some studies found that Cys-C can predict the occurrence of CIN earlier than SCr.Objective:The purpose of this study is to investigate the correlation between preoperative monocyte to lymphocyte ratio(MLR)and the occurrence of contrast induced nephropathy(CIN)after percutaneous coronary intervention(PCI).By using the ROC curve,we can get the optimal value of MLR for predicting CIN.It may provide a valuable way to screen of high-risk groups of CIN,so we can intervene in time before PCI to reduce the incidence of CIN.On the other hand,by analyzing the correlation between Cys-C and SCr during perioperative period,we evaluated Cys-C whether can predict the occurrence of CIN after PCI.Methods:1.Subjects and groupingThis retrospective study included 401 patients with acute coronary syndrome(ACS)who underwent percutaneous coronary intervention(PCI)at Qilu Hospital of Shandong University between June 2016 and January 2017.According to the change of SCr before and after PCI and the definition of CIN,patients are divided into two groups:CIN group(n=21 cases)and non-CIN group(n=380 cases).2.Collection of dataThe baseline demographic characteristics and medication administered of all enrolled patients were recorded:age,sex,height,weight,smoking status,history of present illness,past history,family history,previous and current medications.The procedural characteristics,including the approaches of operation,type and dosage of contrast media,were extracted.The following laboratory measurements of all patients were collected:blood routine,SCr,Cys C,blood urea nitrogen(BUN),low density lipoprotein-cholesterol(LDL-C),fasting blood-glucose(FBG),homocysteine(Hcy),uric acid(UA).Repeat measurements of SCr,Cys C and BUN within 72 hour after PCI were routinely assessed.The results of electrocardiogram and echocardiography were also extracted.Body mass index(BMI)was defined as height(kg)/weight(m)2.Estimated glomerular filtration rate(eGFR)was calculated using a modified MDRD equation for Chinese patients based on Scr and age.The MLR was defined as monocyte count divided by lymphocyte count.3.Statistical analysisSPSS 19.0 was used for the statistical analysis.Continuous variables were expressed as mean ± SD or median(interquartile range).One-sample Kolmogorov-Smirnov test was used to check the normal distribution of continuous variables.Variables with normal distribution were compared using the Student t test,whereas variables with non-normal distribution were compared using the Mann-Whitney U test.Categorical variables were reported as percentages and were compared using the chi-square test.Continuous variables of nonnormal distribution were tested by using the Spearman correlation tests.Multiple logistic regression analysis was used to define the risk factors of CIN.Receiver operating characteristic(ROC)curve analysis was used to evaluate the area under the curve(AUC)and to determine the optimal cutoff points for MLR to predict CIN.P value<0.05 was considered to be significant.Results:1.Basic characteristics of the patients:A total of 401 patients were included in this study,including 283 males(70.6%)and 118 females(29.4%),with an average age of 61.30 ± 10.28 years and an average BMI of 25.63 ± 3.19.There are 280 cases in non-CIN group and 21 cases in CIN group,and the incidence of CIN is 5.24%.There is no significant difference between non-CIN group and CIN group in age,sex,BMI,type of disease,hypertension,diabetes,cerebrovascular disease,hyperlipemia,heart failure,history of smoking,family history of coronary heart disease,approaches of operation,type and dosage of contrast media(P>0.05);The perioperative application of medications,such as aspirin,clopidogrel,calcium channel blockers(CCB),angiotensin converting enzyme inhibitors(ACEI)/angiotensin receptor antagonists(ARB),statins,nitrates,beta blockers,nicorandil,and trimetazidine show no significant difference between the two groups(P>0.05);There is no significant difference in preoperative SCr,BUN,Cys-C,LDL-C,FBG,homocysteine,hemoglobin,monocyte count,lymphocyte count between the two groups(P>0.05);There are significant differences in renal insufficiency,application of diuretic,uric acid and MLR between the two groups(P<0.05).2.Multivariate Logistic regression analysis:Renal insufficiency,application of diuretic,uric acid,and MLR were included in logistic regression analysis,and only MLR showed statistical significance(P<0.05).MLR is an independent risk factor of CIN.3.According to the ROC curve of MLR,0.341 in MLR is the best predictor of the occurrence of CIN.The area of ROC curve is 0.710,the sensitivity and specificity of ROC curve are respectively 0.85 and 0.571.4.The patients are divided into high MLR group and low MLR group based on the ROC curve,and the basic characteristics of the two groups are compared.There are significant differences in sex,hypertension,preoperative SCr,BUN,Cys-C and homocysteine,application of ACEI/ARB and diuretic between the two groups(P<0.05),there is no significant difference in other characteristics.5.Comparison of incidence of CIN between Low MLR group and high MLR group:The low MLR group has 332 patients,including 9 cases of CIN,in which the incidence of CIN was 2.7%;high MLR group has 57 patients,including 12 cases of CIN,in which the incidence of CIN was 17.4%.The incidence of CIN in high MLR group was significantly higher than that in low MLR group(P<0.001).6.The correlation between Cys-C and CIN:The change of Cys-C is positively correlated with the change of SCr by using Spearman correlation analysis,in which the correlation coefficient is 0.494 and it has statistical significance(P<0.001).That is to say,the changes of Cys-C and SCr are in the same direction.Therefore Cys-C is of predictive value to CIN.Conclusions:1.Renal insufficiency,application of diuretic,uric acid and MLR are the risk factors of CIN,and MLR is the independent risk factor of CIN.2.0.341 in MLR is the best predictor of the occurrence of CIN,and the incidence of CIN in high MLR group was higher than that in low MLR group.3.The change of Cys-C is positively correlated with the change of SCr,and Cys-C is of predictive value to CIN.