| BackgroundClinical for ischemic heart disease, not surgical correction of congenital heart disease and idiopathic cardiomyopathy caused by irreversible end-stage heart failure, alternative methods of treatment is limited, for progression to end-stage heart failure, cardiac allograft is still the most effective means of treatment. Forecasting, to the middle of the twentieth century, half of the surgery will be replacement organs. In the world more than 10 million people have accepted the heart transplantation and the number is increasing by an annual rate of more than 5000 cases,2014, only the mainland of China has been implemented heart transplantation of nearly 300. In carrying out the most heart surgery,need to use the technique of extracorporeal circulation, cardiopulmonary bypass,can cause the release of inflammatory cytokines, leading to immune and inflammatory response and acute kidney injury is one of the most important complications.With the development of science and technology, the technology of operation and perioperative management,success is still nearly 30% of patients after heart transplantation face the threat of acute kidney injury. 1%-2% of patients need blood purification treatment, early diagnosis is the key to early treatment, to reduce the case fatality rate. Always in clinical work; the blood creatinine (serum creatinine, Scr) increases as the standard of diagnosis of AKI, however with Scr to assess renal damage degree has the following limitations:first of all,the Scr levels by gender, age, weight, eating, muscle meat, drug metabolism and the influence of such factors as;Second, Scr only with glomerular filtration rate(glomerular filtration rate, GFR), cannot reflect the renal tubular injury and degree of; Again, in the process of cardiac surgery, the body is unsteady. In the unsteady serum creatinine levels cannot truthfully reaction glomerular filtration function, and the evaluation of urine to exclude capacity insufficiency,the influence factors such as the use of diuretics. Only when kidney function decline significantly increased, and is strongly influenced by renal tubular secretion, usually in the kidney damage after 2-3d will appear the changes of serum creatinine. Therefore,early diagnosis of cardiac extracorporeal circulation postoperative AKI perioperative care plays an important role on the heart.In recent years, a large number of clinical studies on Kim-1 and Cys-C. Compared with Scr, these new biomarkers can earlier find AKI,and can predict whether a patient needs in different degrees of renal replacement therapy (RRT) or death.Cys-C is composed of 120 a mino-acid bioactive molecules, is a kind of endogenous alkaline non glycosylated protein, relative molecular mass is small, glomerular filtration membrane can be most free filtration, in the proximal tubuleepithelial cell metabolism, not to be released in production, and not from renaltubular reabsorption in the blood; At the same time, Cys-C is not affected by age, kidney function is damaged, factors such as hypertension, atherosclerosis, and diabetes, are different people heart surgery a more reliable predictor. Postoperative ischemic heart low perfusion in the proximal tubule function structure damage, heavy absorption of small molecules trace protein function decline, Cys-C concentration in urine can rise up to 200 times, are sensitive markers of renal tubular damage, is associated with the severity of AKI, and conventional storing urine Cys-C molecules with high stability, convenient measurement. In previous research, we have explored the pros and cons of the diagnostic value in monitoring after cardiac surgery in patients with AKI Scr and serum Cys-C,found a finite value of AKI of Cys-C in the early diagnosis of heart bypass surgery, was detected after AKI progression and duration of meaningful, Scr of postoperative early stage diagnosis of AKI is sensitive, postoperative first day of Scr of AKI still important diagnostic value. However, the combined diagnosis of the two can have a stronger sensitivity and specificity? Is the starting point of this study.Kim-1 is expressed in a protein on the surface of the T cells, T cell function regulation and immune response process. Acute kidney injury, in renal proximal tubule epithelial cells and repair damaged when there is significant expression and release, in glomerular and renal tubular mesenchymal cells without the express, and tubular interstitial inflammation and fibrosis, there is a certain relationship. Kim-1 express positive proximal renal tubular epithelial cells can be transformed into phagocytes, devouring apoptotic cells and cell fragments,promoting apoptosis cells of tubular cells regeneration and damage. Kim-1 do not express normal kidney tissues, kidney tissue damage high expression, and maintain the characteristics of the epithelium to injury repair. Therefore, Kim-1 level in urine is not only the biomarkers of kidney injury, also can predict risk of acute tubular necrosis, is acute kidney injury practical biological markers, as early biomarkers of AKI may have a wide prospect of clinical application. The current study of Kim-1 diagnostic boundary value is less, has not yet been widely clinical application. Animal experiments showed that Kim-1 than rely on the Scr and urine amount of RIFLE and AKIN diagnosis method, can be more early diagnosis of AKI. Literature reported heart surgery patients with concurrent the incidence of adverse reactions in the process of comorbid AKI 5%-5%, once the concurrent AKI patients hospitalized time and ICU monitoring were significantly prolonged, patients with significantly higher mortality rate.Currently existing multiple single center clinical trials research Kim-1 in the diagnosis of cardiac surgery with AKI ability, but the sample size is limited, the conclusion of the research ability of diagnosis of AKI Kim-1 is differ, Kim-1 with AKI analysis of the relationship still needs further validation.PurposeProspective study different time points after extra corporeal circulation in heart surgery in patients with blood samples of Cys-C, the change of urine Kim-1, evaluation of three indicators, respectively, in the heart diagnostic value in acute kidney injury after extracorporeal circulation operation.Method1. The dynamic changes of serum Cys-C and Urine Kim-1 concentration after cardiopulmonary bypassProspectively collected nanfang hospital in October 2013-October 2014 in cardiothoracic surgery under extracorporeal circulation of material of 82 cases of cardiac surgery patients collected in patients with preoperative and postoperative 2h, 4h,6h,12h,24h,48h 3ml of blood specimen, Scr using enzymatic detection, Cys-C particle transmission immune turbidimetric method (Da Cys C kit, Denmark-koCytomation company) detection, all at the same time in HITACHI: 717045 full automatic biochemical analyzer for testing. By using enzyme-linked immunosorbent (ELISA) detection of urine Kim-1 (R&D) in America, are averaging after hole, avoid the urine volume of urine Kim-1 level, the influence of the results of the monitoring urine creatinine correction. Grouping cooperation seminar standard reference to Amsterdam in 2005 acute renal injury criteria(AKIN):Scr increase from baseline to >26.5mol/L (0.3mg/dL) or increase to the baseline value of 1.5 to 1.5 times, divided into acute kidney injury group, the kidney injury.2. Diagnostic value of combined diagnosis with Scr and serum Cys-C for acute kidney injury after cardiopulmonary bypassBased on partially heart extracorporeal circulation detection post operatively, Scr and Cys-C values. Using the receiver work area under curve (AUC-ROC) evaluation of Cys-C, Scr, or the two joint respectively on the heart after extracorporeal circulation operation early diagnosis value of AKI, grouping criteria same as part 1.3.Diagnostic value of urinary Kim-1 for acute kidney injury after cardiopulmonary bypass:a meta-analysisBy computer retrieval Medline, EMBASE, the Cochrane library, Web Of Science Database, Elsevier Science Direct Database, CNKI and VIP Database, a Database Often thousand, retrieval Kim-1 in patients with postoperative acute kidney injury in early diagnosis Of clinical trial, the quality evaluation methods Of the study on diagnostic accuracy (QUADAS) evaluation Of literature quality, STATA 12.0 and Meta-Disc version 1.4 software for data analysis. Statistical heterogeneity by chi-square test, significant level of alpha= 0.05. Heterogeneity caused by comes from the threshold effect, using the logarithmic sensitivity (1-specific degrees) and logarithmic Spearman correlation coefficient of the evaluation, the threshold effect caused by heterogeneous effect to evaluate I2 and H were used respectively to statistics.I2<50% judged heterogeneity is low, I2>75% when judged to be significant heterogeneity. Heterogeneity I2<75% when using fixed effects model, whereas a random effects model. The Meta-analysis of Disc threshold effect, using STATA explore sources of heterogeneity, combine statistic of diagnostic test, included specificity, positive likelihood ratio and negative likelihood ratio and diagnosis odds ratio, the area under the curve and its 95% confidence interval (CI). Publication bias using STATA map funnel qualitative and quantitative discriminant criterion and Egger linear regression method.Result1. In AKI group:2h after Scr began to rise, compared with no-AKI group, postoperative 12h increased significantly (P=0.045<0.05), to reach peak around 24h, the height of the 48h showed a trend of gradual decline; Compared with no-AKI, postoperative 4h blood Cys-C level increased significantly (P=0.01<0.05), to reach peak around 6h, the height of the 48h to still maintain a high level; Urine Kim-1/Ucr level rising trend since 2h after surgery, compared with no-AKI,2h after surgery can be showed significantly higher (P<0.05), to reach peak around 12h,48h after 12h to continue to maintain at a high level.2. With preoperative Cys-C Scr, blood, urine, Kim-1/Ucr compared postoperative 2h Scr were significantly increased (P<0.05), and serum Cys-C at postoperative 4h significantly higher (P<0.05); postoperative 6h urine Kim-1/Ucr compared with preoperative have statistical significance (P<0.05).3. ROC curve analysis showed that:the 24h Scr in the diagnosis performance of acute kidney injury after cardiopulmonary bypass is excellent, ROC-AUC is 0.99; Postoperative 6h serum Cys-C in the diagnosis performance of AKI is excellent, ROC-AUC is 0.95; Postoperative 6h diagnostic value of combined diagnosis with Scr and serum Cys-C for AKI reflects the excellent performance, ROC-AUC is 0.95; The sensitivity of diagnosis AKI by postoperative 6h Cys-C is 0.98, specificity is 1, higher value than Scr performance during the same period, and compared with same time diagnostic value of combined diagnosis with Scr and serum Cys-C for AKI, the sensitivity, specificity, no obvious difference.4. Sensitive analysis to explore the sources of heterogeneity, the sensitivity analysis eliminate Han, than merger sensitivity is 0.87 (95% CI,0.81 0.81) P=0.5776,I2=0.0%, specificity is 0.78 (95% CI,0.74 0.74) P=0.00,I2=87.1%, positive likelihood ratio is 4.07 (95%CI,2.70 7.12) P=2.70,I2=78.2% and negative likelihood ratio is 0.19 (95% CI,0.130.13), P=0.7303,I2=0.0%, diagnostic odds ratio is 28.03 (95% CI,15.95 15.95), P=0.8640, I2=0.0%. Summary area under the receiver-operating curve is 0.9155. Postoperative monitoring point in time with Kim-1 as a indicator for subgroup analysis, the results show that postoperative 2h Kim-1 in the diagnosis of acute kidney injury after cardiopulmonary bypass, sensitivity is 0.87, specificity is 0.73, diagnosis odds ratio is 21.84, the area under the curve is 0.8954. Postoperative 6 and 12h Kim-1 in the diagnosis of acute kidney injury after cardiopulmonary bypass, sensitivity is 0.89, specificity is 0.76, diagnosis odds ratio is 33.78, the area under the curve is 0.9351.Conclusion1. Postoperative serum Cys-C with earlier accurate diagnosis value than Scr, about 18h, serum Cys-C with more superiority than Scr on monitoring postoperative AKI development condition;2. Diagnostic value of combined diagnosis with postoperative 6h Scr and serum Cys-C for acute kidney injury after cardiopulmonary bypass is excellent, but compared with postoperative 6h serum Cys-C in the diagnosis of AKI, without obvious difference in its sensitivity and specificity, failed in excellent performance for AKI diagnostic.3. Statistical differences between postoperative 2h Scr and the preoperative value, postoperative 12h Scr levels in the experimental and control group showed statistically significant, but has not reached AKI diagnostic criteria, postoperative 24h show excellent diagnostic performance, suggests that Scr in the diagnosis of acute kidney injury after cardiopulmonary bypass affected by the interference factors, pool in sensitivity of AKI diagnostic.4. Compared with preoperative values, although the postoperative 6h urine Kim-1/Ucr show the difference, but the postoperative 2h urine/Ucr AKI diagnosis value is excellent, continues to maintain excellent diagnostic performance to postoperative 48h, it can be detected in big time window, can be used as a good indicator of AKI diagnosis.5. System analysis showed that postoperative 6h to 12h urine Kim-1 in the diagnosis of AKI has high diagnostic accuracy after cardiopulmonary bypass. |
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