| Background:Contrast-induced nephropathy (CIN) was defined as a relative rise in sCr≥25%, or as an absolute increase>44.2umol/L(0.5mg/dL) compare to baseline level within 24-72 hours after the contrast medium excluding other factors that may cause nephropathy.According to the European Society of Urogenital Radilogy(ESUR).In recent years, with gradually increased incidence of coronary heart disease (CHD) and percutaneous coronary intervention operation(PCI) indications of expanding, making contrast media increasingly widely used in cardiovascular PCI. CIN is the third leading cause of acquired acute renal failure in hospital. The statistical results showed that CIN accounted for 12% of acquired acute renal failure. In addition, CIN is a one of the major complication of PCI following stent thrombosis and restenosis. For patients with normal renal function, renal injury caused by contrast agent is reversible, only few paitents develop to renal failure, in need of temporary or permanent hemodialysis treatment. Study shows that for post-PCI patients without chronic renal insufficiency and CIN,1 year mortality is 3%, when combined with chronic renal insufficiency or CIN,1 year mortality is 7%-8%, combined with chronic renal insufficiency and CIN,1 year mortality is as high as 25%.Studies have shown that the incidence of CIN patients without any risk factors for less than 2%, and the incidence of CIN patients can be as high as 50% with one or more risk factors. At present most of the world experts generally think the incidence of CIN is about 12%. Foreign literature reported that the incidence of CIN after PCI in 0%-24%, and also increased along with the increase in risk factors for morbidity. The incidence of CIN is low in patients with normal renal function (0-5%). However, several prospective controlled trials reported an incidence of 12-27% in patients with preexisting renal impairment. The incidence of CIN is low in patients with normal renal function pre-PCI between 0%-5%, and the incidence of CIN in patients with renal insufficiency preoperatively as much as 12%-27%.The pathogenesis of CIN has not completely clear, may be related to the following factors. The contrast into intravascular will cause renal hemodynamic changes, leading to renal blood flow decreases,, and then appeare persistence spasmodic contraction of renal blood vessels, eventually lead to the decrease of the glomerular filtration rate(GFR). The osmotic diuresis action of contrast also can aggravate the renal medullary ischemia anoxic injury. The change of vascular active substances, including increased endothelin(ET) synthesis, nitric oxide(NO) and prostaglandin content decreased, increased formation of oxygen free radicals. In addition, the direct toxicity of the contrast to renal tubular epithelial cells may also play a role in the development of CIN. Risk factors for CIN mainly includes: preoperative renal insufficiency, diabetes, types and dose of contrast agent, and congestive heart failure (grade III or IV), older age, anemia, hypotension, intra-aortic balloon counterpulsation, dehydration and renal toxicity of drug use, etc.Currently, the tests of renal function are commonly used markers of serum creatinine (sCr) and Cytatin C(CyC) two kinds in the clinical. Creatinine is mainly excreted by glomerular, without being renal tubular reabsorption and a small amount of secretion.But the level of sCr easily influenced by gender, age, muscle mass, inflammation, diet and other factors. Serum CyC is reported in recent years that can reflect the early renal damage markers, only by glomerular filtration is cleared, and no renal tubular secretion. Serum CyC that are not affected by gender, age, diet, inflammatory reaction, muscle metabolism and liver diseases, is a kind of ideal to reflect the actual changes in glomerular filtration rate of endogenous markers. CyC is an ideal endogenous markers to reflect the GFR. So, sCr and CyC is currently the most widely used to evaluate the renal function in the clinical by the estimated glomerular filtration rate (eGFR).About the influence of preoperative renal insufficiency and the contrast media in CIN, related studies found that preoperative renal insufficiency, contrast medium volume are very important factors for CIN. The incidence of CIN in patients with eGFR<60 ml/min/1.73m2 (19.2%) is significantly higher than (13.1%) in patients with normal renal function at analysis of 7230 cases of post- PCI by Dangas. At present, the research has show that the nephrotoxic effect of high-osmolar CM is higher in patients with preexisting CKD or in the presence of significant risk factors for CIN than low-osmolar CM or iso-osmolar CM, and has the high incidence of CIN. The benefit of iso-osmolar CM over low-osmolar CM in patients with preexisting CKD or those at high risk for CIN is debatable. Researchs shows, the contrast agent dosage was significantly positively related with CIN, contrast each add 100 ml, with incidence of CIN risk increased by 12%, Related research found that when the contrast media volume>260 ml or>300 ml, the incidence of CIN was a significant rise.At present, to analysis the current research status about the CM/eGFR ratio to predict the CIN after PCI is very rare. Early studies suggested that a maximum acceptable contrast dose (MACD) during PCI operation was 5 times of weight and sCr ratio, following formula:(Contrast ml=5×body weight (kg))/(SCr (mg/dl)). But sCr does not directly on behalf of the renal function, such as women, low weight, older population even with sCr level in the normal range, but the value of eGFR may already very low. So, according to the sCr level to calculate MACD directly in patients after PCI operation is poor accuracy. Therefore, Before using contrast agents, these factors with patient age, gender, the concentration of sCr or CyC should be combined to estimate glomerular filtration (eGFR) with more accuracy, and in order to more comprehensive evaluation of renal function. For above-mentioned reasons, we produced the idea of combination with the CM and eGFR, namely CM/eGFR ratio, through the ratio of CM/eGFR to predict the incidence of CIN after PCI; at the same time to find the critical value of CM/eGFR ratio which is a threshold with clinical diagnostic significance. Moreover, the domestic and foreign clinical research about the ratio of CM/eGFR to predict CIN after PCI and explore a individualized MACD in PCI operation is rare currently.Objective:This article aims to analyze the clinical effect about the CM/eGFR ratio to predict CIN after PCI, and explore the range of a individualized contrast media volume according to preoperative renal function, and provide more evidence of evidence-based medicine to prevent CIN after PCI.Subjects and Method:1. Research population:patients was continuously recruited with coronary heart disease (CHD) between May 2014 and October 2015 in Nanfang hospital cardiology department, and underwent coronary angiography(CAG), percutaneous coronary intervention (PCI).Finally 307 patients were conforming to the inclusion and exclusion criteria following, according to whether CIN happened after PCI is divided into two groups:CIN group (29 cases) and non-CIN group (278 cases).2. Inclusion criteria:(1) All patients were CHD, including stable angina and acute coronary syndrome(ACS). (2) Operationg procedure including elective and emergency PCI. (3) All patients without age limited. (4) Test sCr, CyC at preoperative and postoperative 24-72 h and after 7 days. (5) hydration treatment within 24 h after PCI (1-1.5ml/kg.h).(6) All patients with statins.3. Exclusion criteria:(1) Acute cardiac shock; (2) Severe pneumonia and other inflammation; (3) renal resection or single or End-stage renal disease (including uremia or dialysis treatment); (4) Without hydration treatment within 24 h after PCI; (5) without testing sCr, CyC at preoperative; (6)No PCI operation after CAG; (7) Use contrast media within 7 days before PCI operation; (8) contrast media allergy.4. Baseline information:The follow information including gender, age, weight, type of CHD (stable angina or ACS), diabetes, hypertention, NT-proBNP, cardiac function level grade Ⅲ or Ⅳ, sCr and CyC concentration of preoperative and postoperative, estimated glomerular filtration rate(eGFR). Preoperative medication: ACEI/ARB, metformin, diuretics, CCB. Operation related:aortic balloon counterpulsation (IABP), CM type and volume, perioperative hypotension, postoperative hydration treatment. CM types including IOCM:iodixanol; LOCM: iohexol, iopromide.5. CIN diagnostic criteria:was defined as a relative rise in sCr≥25%, or as an absolute increase≥44.2umol/L(0.5mg/dL) compare to baseline level within 72 hours after the contrast medium excluding other factors that may cause nephropathy.6. eGFR calculation formula: ①Calculation of eGFR on the basis of the sCr, use the corrected standard MDRD formula, eGFRMDRD=186×(sCr) 1.15×age-0.302×1.233 (if female on the basis×0.742).②Calculation of eGFR on the basis of the CyC,use the eGFR group in China formula, eGFRCyC=86×(CyC)-1.132, unit(ml/min/1.73m2)7. CIN predictors:Take the ratio of contrast media and eGFR (CM/eGFR) as prediction index of CIN after PCI. There are two predictors according to two diferent eGFR by sCr, CyC. So, there wre two predictors:① The ratio of CM/eGFRMDRD,② The ratio of CM/eGFRcyc8. Statistical approach:All the statistical analyses were performed with SPSS 19.0. Continuous variables with normal distribution were expressed as mean± standard. Categorical variables were expressed as frequency, a univariate analysis was performed using an unpaired t-test or Mann-Whitney U test for the continuous variables, and a chi-square test for the categorical variables, respectively. A multivariate logistic regression analysis was used to assess the correlation among CIN risk factors, whose statistical significance was demonstrated on a univariate analysis at a level of p<0.05. An analysis of the receiver operating characteristic (ROC) curve was conducted to determine the cut-off value and area under the curve(AUC) of the CM/eGFRcyc and CM/eGFRMDRD for predicting CIN.All statistical analysis take P<0.05 for statistically difference.Results:1. Overall dataA total of 307 cases meet eligibility criteria, CIN occurred in 29 patients with rate 9.4%(29/307). Average age 59.7±11.9 (25-87) years, age≥70 years were 20.8% (64 cases), female 21.5%(66 cases), average weight 67.6±11.2 (Kg), diabetes 41.7%(128 cases), hypertensions 62.2%(191 cases), ACS 81.4%(250 cases), perioperative hypotension 18.2%(58 cases), postoperative IABP 4.2%(13 cases), cardiac function level≥Ⅲ 16.3%(50 cases).2. Baseline data comparison between two groupsTwo groups in age, weight, perioperative hypotension, postoperative IABP, diuretics, cardiac function level≥Ⅲ, NT-proBNP, contrast media volume (CM), preoperative sCr, CyC, eGFRMDRD, eGFRcyc and CM/eGFRMDRD, CM/eGFRcyc ratio had significant difference (P< 0.05). While, there was no statistical difference at the two groups about gender, age≥70(y), ACS, diabetes, hypertension, history of PCI, ACEI/ARB, CCB, metformin, (P> 0.05).3. Comparison of sCr, CyC of post-PCI between two groupsIn CIN group of preoperative and postoperative 24-48 h,48-72h of sCr was 120.1±55.7,150.4±72.9,168.6±91.4 (umol/L), CyC was 1.46±0.6,1.72±0.63, 1.99±0.79 (mg/L), statistics show that:sCr, CyC in 48-72 h of post-operative is significantly higher than peroperative (P<0.05).In non-CIN group of preoperative and postoperative 24-48 h,48-72h of sCr was 91.4±35.9、87.3±33.3、93.8±36.6 (umol/L), CyC was 1.12±0.32、1.14±0.34、 1.24±0.38(mg/L),statistics:there was no statistical difference at preoperative, postoperative 24 h,48-72h of sCr. But CyC in 48-72h of post-operative is significantly higher than preoperative(P<0.05). Although 48-72h CyC of post-operative was significant higher than preoperative in non-CIN group, but was lower than the change of CIN group.4. CIN incidence in different pre-PCI renal functionAccording to different preoperative eGFR, the eGFRMDRD and eGFRcyc was devided into 3 groups, means eGFR≥90、60-90、≤60. The 3 groups incidence of CIN in eGFRMDRD were 3.2%,14%,38.5% respectively. It has significant differences between the any two groups among the three groups (P< 0.005). While, the 3 groups incidence of CIN in eGFRcyc were 4.3%、5.6%、30.2% respectively. There is significant differences between eGFRcyc≤60 group and eGFRcyc≥90 group or 60-90 group (P<0.001), while comparison about eGFRCyC≥90 group and 60-90 group without significant differences (P>0.05). Therefore, the worse preoperative kidney function, the higher the incidence of CIN.5. Comparison of CIN incidence in different contrast volume and osmoticGroup by contrast type, LOCM 202 cases with CIN incidence 7.4%(15/202), IOCM 105 cases with CIN incidence 13.3%(14/105), there was no significant difference between groups(P>0.05). Group by contrast volume,≥250 ml 30 cases with CIN incidence 23.3%(7/30),<250ml 277 cases with CIN incidence 7.9% (22/277), It was significant difference between the two groups (P=0.006).As a result, the bigger the volume of CM the higher the incidence of CIN, and has no significant difference with the LOCM and IOCM.6. CIN related risk factorsWith other risk factors fixed in stepwise multivariate Logistic regression analysis, the ratios of CM/eGFRMDRD and CM/eGFRcyc were respectively entered into analysis model; As a result:Age (OR 1.062; P=0.011), cardiac function≥Ⅲ level (OR 6.845;P<0.001), used CCB (OR 0.038; P<0.001), CM/eGFRMDRD (OR 3.735; P<0.001) in CM/eGFRMDRD group; and Age (OR 1.058; P=0.015), cardiac function≥Ⅲ level (OR 4.708; P=0.002), postoperative IABP(OR 5.472; P=0.019), CM/eGFRcyc (OR 2.528; P<0.001) in CM/eGFRcyc group were respectively independent risk predictors for CIN.7. Evaluation for Predictors of CINThe ROC curve was performed using CM/cGFRMDRD and CM/eGFRcyc to assess its ability to predict the development of CIN after PCI. ROC curve shows, the AUC of CM/eGFRMDRD ratio is 0.838 and the AUC of CM/eGFRCyc ratio is 0.805. There is no significant difference both the AUC of CM/eGFRcyc and CM/eGFRMDRD by Z test (P<0.001). The ratios of CM/eGFRMDRD and CM/eGFRcyc cut-off points value were 2.095,2.71 respectively. Sensitivity, and speciality were 79.3%,76.3% respectively. Further analysis showed that the incidence of CIN in patients of CM/eGFRMDRD≥2.095 or CM/eGFRCyC≥2.71,25.8%(23/89) was significantly higher than the incidence of CIN in patients of CM/eGFRMDRD< 2.095 or CM/eGFRcyc<2.71,2.75%(6/218) (P< 0.001).ConclusionThe incidence of CIN after PCI was 9.4% in this study. Both CM/eGFRMDRD and CM/eGFRcyc were found to be independent predictors for CIN by Logistic regression analysis. MACD was 2.095 times of the eGFRMDRD or 2.71 times of the eGFRcyc when use the ratio of CM/eGFRMDRD or CM/eGFRCyC to predict CIN. It will be higher sensitivity and specificity when exceed the best appropriate ratio. Therefore, the clinical application of CM/eGFRMDRD or CM/eGFRcyc is a good method to evaluate the MACD and predict CIN after PCI currently, and without significant differences between the two predictors. |
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