with the development of enhanced radiation technology and interventional techniques , effective diagnosis and treatment are possible for patients with coronary and other peripheral vascular diseases . however , therapeutic effects always come with complications , including vascular perforation , dissection , and contrast - induced nephropathy ( cin ) . among these complications , cin has been demonstrated to be associated with irreversible renal insufficiency , prolonged hospitalization , and high cost . additionally , cin has unfavorable early and late prognosis . therefore , it is important to diagnose cin and provide treatment as soon as possible , which depends on the early diagnosis . contrast - induced nephropathy , also referred to as contrast - induced acute kidney injury , has become the third leading cause of hospital - acquired acute kidney injury . half of these cases are caused by repeated exposure to contrast media during cardiac catheterization and coronary angiography ( cag ) . contrast - induced nephropathy is defined as an increase in serum creatinine ( scr ) concentration > 0.5 mg / dl or a minimum of 25% increase from baseline within 72 h after contrast administration , without evidence of other causes . detection of serum creatinine is the foundation for the diagnosis of cin ; however , the scr level may not be determined quickly enough to reflect decreased renal function , and scr level is affected by factors such as age , sex , and muscle mass . in conclusion , scr is not a perfect glomerular filtration rate ( gfr ) biomarker and is not sensitive enough to detect early changes in gfr . thus , there is great need for a more sensitive and reliable biomarker for predicting the occurrence of acute kidney injury ( aki ) or cin . numerous clinical trials have been sought to find discover an appropriate biomarker for early and precise assessment of renal function [ 68 ] . disappointingly , many biomarkers have been confirmed to be useless , including neutrophil gelatinase - associated lipocalin , urinary liver type fatty acid - binding protein ( l - fabp ) , and urinary kidney injury molecule 1 . serum cystatin c ( cys c ) is a non - glycosylated protein with low molecular mass ( 13 kda ) . it is a cysteine protease inhibitor synthesized by all nucleated cells and released into the blood by glomerular filtration . most importantly , external factors have little effect on the serum level of cys c. previous studies have demonstrated its utility in detection of diabetic mellitus and hypertensive nephropathy . in the present study we sought to determine the ability of cys c to predict the occurrence of cin in patients who underwent cag and intervention , and we compared the sensitivity and specificity of cystatin c and serum creatinine in the diagnosis of cin . from january 2015 to may 2015 , a total of 300 consecutive patients who underwent only diagnostic coronary angiography for suspected coronary heart disease were enrolled in the study . it was funded by the national natural science foundation of china ( no . 81200153 ) , the science foundation of health department , sichuan province ( no . 20120213 ) , the science foundation of science and technology department , sichuan province ( no . 2015sz0180 ) , and the science foundation of the science and technology department , sichuan province ( no . the exclusion criteria included : 1 ) patients with chronic nephropathy ( ckd stage 2 to 4 ) ; 2 ) patients with other contrast exposure within 1 week , or exposure to nephrotoxic drugs ; 3 ) patients with previous kidney transplantation , cardiac dysfunction , thyroid disorder , or cancer ; 4 ) patients who were unable to understand the study content or provide consent ; 5 ) patients younger than 18 or older than 80 years old ; and 6 ) patients simultaneously participating in other studies . patient data were recorded for feasibility analysis at admission , including sex , age , body mass index ( bmi ) , left ventricular ejection fraction ( lvef ) , hypertension , and diabetes mellitus , as well as use of oral medicines , especially angiotensin - converting enzyme inhibitors / angiotensin receptor blockers ( acei / arb ) , and statins . fasting baseline renal function and serum level of cys c were measured as basal indicators 24 h before cag . as another important evaluation indicator , estimated gfr ( egfr ) was calculated by the levey modification of the modification of diet in renal disease ( mdrd ) formula . a standard dose ( 35 ml / kg ) of iodinated contrast medium ( iohexol , ge pharmaceutical , shanghai ) was used . in the process of angiography , we recorded the operation time and the infusion dose of contrast medium . serum samples were collected at 12 , 24 , and 48 h after cag for measuring postoperative levels of cys c and creatinine . all blood samples were analyzed by the clinical laboratory in our hospital . according to the definition of cin , we calculated the change in creatinine and confirmed the occurrence of cin . then , all the patients were assigned into 2 groups based on whether cin occurred . after grouping , we compared the collected demographics , medication usage , exposure to contrast medium , and serum levels of cys c and creatinine at different time points . results are expressed as mean  standard deviation ( sd ) for continuous variables and frequencies for categorical variables . differences between groups were examined by nonparametric test and chi - square test for continuous and categorical variables , respectively . other variables that were significantly associated with outcome were fed into the model in a stepwise procedure . an alpha value of 0.05 , corresponding to a p value < 0.05 , served as the criterion for establishing statistical significance . the diagnostic sensitivity and specificity for the early diagnosis of cin based on the serum level of cys c and scr at 24 h from january 2015 to may 2015 , a total of 300 consecutive patients who underwent only diagnostic coronary angiography for suspected coronary heart disease were enrolled in the study . it was funded by the national natural science foundation of china ( no . 81200153 ) , the science foundation of health department , sichuan province ( no . 20120213 ) , the science foundation of science and technology department , sichuan province ( no . 2015sz0180 ) , and the science foundation of the science and technology department , sichuan province ( no . the exclusion criteria included : 1 ) patients with chronic nephropathy ( ckd stage 2 to 4 ) ; 2 ) patients with other contrast exposure within 1 week , or exposure to nephrotoxic drugs ; 3 ) patients with previous kidney transplantation , cardiac dysfunction , thyroid disorder , or cancer ; 4 ) patients who were unable to understand the study content or provide consent ; 5 ) patients younger than 18 or older than 80 years old ; and 6 ) patients simultaneously participating in other studies . patient data were recorded for feasibility analysis at admission , including sex , age , body mass index ( bmi ) , left ventricular ejection fraction ( lvef ) , hypertension , and diabetes mellitus , as well as use of oral medicines , especially angiotensin - converting enzyme inhibitors / angiotensin receptor blockers ( acei / arb ) , and statins . fasting baseline renal function and serum level of cys c were measured as basal indicators 24 h before cag . as another important evaluation indicator , estimated gfr ( egfr ) was calculated by the levey modification of the modification of diet in renal disease ( mdrd ) formula . a standard dose ( 35 ml / kg ) of iodinated contrast medium ( iohexol , ge pharmaceutical , shanghai ) was used . in the process of angiography , we recorded the operation time and the infusion dose of contrast medium . serum samples were collected at 12 , 24 , and 48 h after cag for measuring postoperative levels of cys c and creatinine . all blood samples were analyzed by the clinical laboratory in our hospital . according to the definition of cin , we calculated the change in creatinine and confirmed the occurrence of cin . then , all the patients were assigned into 2 groups based on whether cin occurred . after grouping , we compared the collected demographics , medication usage , exposure to contrast medium , and serum levels of cys c and creatinine at different time points . results are expressed as mean  standard deviation ( sd ) for continuous variables and frequencies for categorical variables . differences between groups were examined by nonparametric test and chi - square test for continuous and categorical variables , respectively . other variables that were significantly associated with outcome were fed into the model in a stepwise procedure . an alpha value of 0.05 , corresponding to a p value < 0.05 , served as the criterion for establishing statistical significance . the diagnostic sensitivity and specificity for the early diagnosis of cin based on the serum level of cys c and scr at 24 h were calculated by use of roc curve analysis and auc assessment . a total of 300 patients ( 179 males , 121 females ) with a mean age of 63.479.92 were included in the final study . according to the definition of cin , patients with a > 25% relative increase of serum creatinine , or an increase in concentration of serum creatinine of at least by 44 mmol / l from the baseline 48 h after cag , we analyzed and compared the demographics of the 2 groups . as is shown in table 1 , patients in the cin group were significantly older than those in the non - cin group ( p=0.048 ) , and the cin group had a higher proportion of females than the non - cin group ( p=0.037 ) . however , the differences in the ratio of hypertension , diabetes mellitus , smoking , and cardiac dysfunction were not statistically significant . medication history was also recorded to analyze the effect on renal function , though there were no obvious distinctions between the 2 groups ( all p>0.05 ) . previous researchers have used infusion dose of contrast medium and the exposure time as important indicators of cin , and we demonstrated the importance of these 2 indicators in our study . patients in the cin group received significantly larger doses of contrast medium ( p=0.040 ) and the operation time was longer compared to the non - cin group . comparison of basal renal function and serum level of cys c showed no significant differences between the 2 groups . as an important procedure in our study , we measured the serum levels of creatinine and cystatin c at various time points . compared vertically , the rise in serum cys c was the maximum at 24 h , which was significantly higher than baseline ( p<0.001 ) . then , the level declined , but still remained higher at 48 h ( p<0.01 ) . the serum level of creatinine in the cin group peaked at 48 h ( p<0.001 ) and was not significantly different at 24 h. egfr had decreased at 24 h and had even more obviously decreased at 48 h ( p<0.001 ) . it is obvious that the change in serum level of cys c occurred prior to the change in serum level of creatinine . in the non - cin group , the differences in scr and cys c before and after the procedure were both non - significant . compared horizontally , the difference in cys c level between the 2 groups became apparent at 24 h ( p<0.001 ) and lasted until 48 h. the serum level of scr in the cin group was significantly higher than that in the non - cin group only at 48 h , and the difference was not obvious at 24 h. moreover , compared with non - cin group , egfr decreased from 24 h to 48 h in the cin group , and both differences were significant ( p<0.001 ) . table 2 shows that the change in serum level of cys c became significantly different before that of scr . to study the significance of cys c and scr in cin the area under the curve ( auc ) of cys c at 12 h and 24 h was 0.735 ( 95% ci : 0.6480.823 , p=0.000 ) and 0.928 ( 95% ci : 0.8700.987 , p=0.000 ) , respectively , and the optimum cut - off level was 1.315 mg / l ( sensitivity=79.3% and specificity=55.4% ) and 1.55 mg / l ( sensitivity=82.8% and specificity=97.8% ) , respectively . the auc of changes in cys c between baseline and 12 h and 24 h were 0.758 ( 95% ci : 0.6680.847 , p=0.001 ) and 0.936 ( 95% ci : 0.8790.992 , p=0.000 ) , respectively , and the optimum cut - off level was 0.185 mg / l ( sensitivity=79.3% and specificity=95.3% ) and 0.26 mg / l ( sensitivity=89.7% and specificity=95.6% ) , respectively . the auc was 0.923 ( 95% ci : 0.8750.972 , p=0.000 ) and the optimum cut - off level was 17.15% ( sensitivity=79.3% and specificity=87.8% ) . when we chose the serum level of creatinine at 24 h for roc analysis , the auc was 0.733 ( 95% ci : 0.6400.825 , p<0.001 ) and the optimum cut - off level was 73.55 mol / l ( sensitivity=89.7% and specificity=43.5% ) . according to the results in table 3 , although the aucs of cys c at 24 h and cys c changes at 24 h were similar , serum cys c with concentration changes > 0.26 mg / l had higher sensitivity ( 89.7% vs. 82.8% ) but lower specificity ( 95.6% vs. 97.8% ) for differentiating cin and non - cin . a total of 300 patients ( 179 males , 121 females ) with a mean age of 63.479.92 were included in the final study . according to the definition of cin , patients with a > 25% relative increase of serum creatinine , or an increase in concentration of serum creatinine of at least by 44 mmol / l from the baseline 48 h after cag , we analyzed and compared the demographics of the 2 groups . as is shown in table 1 , patients in the cin group were significantly older than those in the non - cin group ( p=0.048 ) , and the cin group had a higher proportion of females than the non - cin group ( p=0.037 ) . however , the differences in the ratio of hypertension , diabetes mellitus , smoking , and cardiac dysfunction were not statistically significant . medication history was also recorded to analyze the effect on renal function , though there were no obvious distinctions between the 2 groups ( all p>0.05 ) . previous researchers have used infusion dose of contrast medium and the exposure time as important indicators of cin , and we demonstrated the importance of these 2 indicators in our study . patients in the cin group received significantly larger doses of contrast medium ( p=0.040 ) and the operation time was longer compared to the non - cin group . comparison of basal renal function and serum level of cys c showed no significant differences between the 2 groups . as an important procedure in our study , we measured the serum levels of creatinine and cystatin c at various time points . compared vertically , the rise in serum cys c was the maximum at 24 h , which was significantly higher than baseline ( p<0.001 ) . then , the level declined , but still remained higher at 48 h ( p<0.01 ) . the serum level of creatinine in the cin group peaked at 48 h ( p<0.001 ) and was not significantly different at 24 h. egfr had decreased at 24 h and had even more obviously decreased at 48 h ( p<0.001 ) . it is obvious that the change in serum level of cys c occurred prior to the change in serum level of creatinine . in the non - cin group , the differences in scr and cys c before and after the procedure were both non - significant . compared horizontally , the difference in cys c level between the 2 groups became apparent at 24 h ( p<0.001 ) and lasted until 48 h. the serum level of scr in the cin group was significantly higher than that in the non - cin group only at 48 h , and the difference was not obvious at 24 h. moreover , compared with non - cin group , egfr decreased from 24 h to 48 h in the cin group , and both differences were significant ( p<0.001 ) . table 2 shows that the change in serum level of cys c became significantly different before that of scr . to study the significance of cys c and scr in cin , we chose the serum levels at different time points for roc analysis . the area under the curve ( auc ) of cys c at 12 h and 24 h was 0.735 ( 95% ci : 0.6480.823 , p=0.000 ) and 0.928 ( 95% ci : 0.8700.987 , p=0.000 ) , respectively , and the optimum cut - off level was 1.315 mg / l ( sensitivity=79.3% and specificity=55.4% ) and 1.55 mg / the auc of changes in cys c between baseline and 12 h and 24 h were 0.758 ( 95% ci : 0.6680.847 , p=0.001 ) and 0.936 ( 95% ci : 0.8790.992 , p=0.000 ) , respectively , and the optimum cut - off level was 0.185 mg / l ( sensitivity=79.3% and specificity=95.3% ) and 0.26 mg / l ( sensitivity=89.7% and specificity=95.6% ) , respectively . the auc was 0.923 ( 95% ci : 0.8750.972 , p=0.000 ) and the optimum cut - off level was 17.15% ( sensitivity=79.3% and specificity=87.8% ) . when we chose the serum level of creatinine at 24 h for roc analysis , the auc was 0.733 ( 95% ci : 0.6400.825 , p<0.001 ) and the optimum cut - off level was 73.55 mol / l ( sensitivity=89.7% and specificity=43.5% ) . according to the results in table 3 , although the aucs of cys c at 24 h and cys c changes at 24 h were similar , serum cys c with concentration changes > 0.26 mg / l had higher sensitivity ( 89.7% vs. 82.8% ) but lower specificity ( 95.6% vs. 97.8% ) for differentiating cin and non - cin . contrast - induced nephropathy is a well - known complication that can be observed after some enhanced radiologic and angiographic examinations and treatments . the injury is generally mild and transient but can result in lasting renal dysfunction and it is associated with increased morbidity and mortality . one is the influence of renal hemodynamics caused by contrast medium exposure and the other is the direct cytotoxicity of contrast medium to renal tubular epithelial cells . in addition , there are no effective therapies for the acute kidney injury caused by contrast medium , so the only option is to prevent it from happening . nowadays , serum level of creatinine is widely used and recognized as a diagnostic clinical indicator of cin . however , scr could be affected by numerous factors like age , sex , and muscle mass . because of the reserve capacity of the kidneys , concentrations of scr can be within the reference range with a certain degree of impaired renal function . in our study , the level of scr increased significantly 48 h after exposure and was obviously higher than in the non - cin group ( p<0.001 ) . therefore , scr is not efficient and accurate enough as a diagnostic indicator of cin . these limitations prompted us to look for another indicator that can reflect damaged renal function in early stages . the results showed that the serum level of cys c significantly increased at 24 h in cin patients , which was before the increase in scr . the variation tendency of cys c in the non - cin group was not obvious , as opposed to the increase in the cin group ( p=0.121 vs. p<0.001 ) . cys c is a 13-kda non - glycosylated protein that is a cysteine protease inhibitor . it is produced by almost all nucleated cells at a constant rate and removed from the blood by glomerular filtration . the kidneys are the only organs that clear cys c , and the serum level of cys c only depends on gfr . therefore , in theory , the concentration change of cys c can reflect the change of gfr more sensitively than scr . bachorzewska - gajewska et al . found the same variation tendency of cys c after contrast medium exposure . their study including 410 patients with chronic kidney disease indicated that cys c is a reliable biomarker and predictor for the early diagnosis of cin . however , the form of cys c used for cin diagnosis is still in dispute . our study again verified the significant predictors of cin , including age , female sex , the dose of contrast medium , and the exposure time . most importantly , we revealed the potential association between the increase of cys c and the occurrence of cin . a certain increase of the concentration of cys c is sensitive and specific for the prediction of cin after contrast medium exposure . despite of the achievements of our study firstly , we only included patients with normal renal function at baseline , which limited the observations of the significance of cys c in patients with chronic kidney disease . then , we excluded patients who underwent pci from our study , leading to insufficient contrast medium exposure . in addition , we analyzed the different forms of cys c for the early diagnosis of cin and results showed similar significance among these indicators . therefore , the best form of cys c for the diagnosis of cin still remains uncertain . in conclusion , our study demonstrated that the change in concentration of cys c is superior to scr as a biomarker in the early detection of cin . we found that the changed concentration of cys c is superior to scr as a biomarker in the early detection of cin .
backgroundcontrast - induced nephropathy is acute kidney injury caused by contrast medium exposure . 
 serum creatinine is the clinical diagnostic standard , but it does not yield quick results . the serum level of cystatin c is stable and it can reflect renal function sensitively . the study aimed to assess the usefulness of cystatin c for early diagnosis of contrast - induced nephropathy in patients undergoing coronary angiography.material/methodswe included 300 patients who underwent cag . according to the scr at 48 h , patients were divided into 2 groups : cin group and non - cin group . 
 their demographics and basal renal function were recorded . 
 changes in scr , cys c , and e gfr were compared at the same time . 
 roc analysis was used to assess the sensitivity and specificity of cys c in the early diagnosis of cin.resultscomparison of basal renal function and serum level of cys c showed no significant differences between the 2 groups . 
 serum level of cys c increased significantly at 24 h ( p<0.001 ) , and scr increased significantly at 48 h. roc analysis showed that the auc of the change in cys c between baseline and 24 h was 0.936 ( 95% ci : 0.8790.992 , p=0.000 ) and the optimum cut - off level was 0.26 mg / l ( sensitivity=89.7% and specificity=95.6%).conclusionsthe concentration change of cys c is better than scr as a biomarker in the early detection of cin .