Objective To investigate the applicability of Cys C-based formulas for prediction of GFR in Chinese patients with CKD.Methods A total of 176 adult patients with CKD including 90 males and 86 females collected from 4 hospitals located in different geographic regions of China (Beijing,Shanghai,Dalian and Changsha) were enrolled in this study from September 2007 to July 2009.The rGFR was measured using 99mTc-DTPA clearance rate two-sample method.Cystantic C was measured by PETIA and PENIA respectively.The results of eGFR in the Larsson formula,Grubb formula,Hoek formula,Filler formula,Stevens formula and Hojs formula were compared with the rGFR to evaluate the calculation coherence,bias,precision,accuracy and the performance of correct phasing of the formulas.Results The mean 99mTc-DTPA clearance was [40.70 ( 19.09 - 86.49)] ml · min-1 · ( 1.73m2 ) -1.Significant difference was witnessed in the evaluation of GFR estimation formulas calculated by PETIA and PENIA (P ＜0.01).ICC and Spearman correlation analysis revealed a significant correlation between eGFR and rGFR.The ICCs of eGFR and rGFR ranged from 0.874 to 0.938.Compared with rGFR,the 30％ accuracy of all the eight evaluation formulas using PETIA and PENIA method were lower than 60％.The percentages of correct phasing in all the 5 stages of CKD were not ideal.With these formulas,percentages of correct phasing from CKD stage 2 to CKD stage 4 were lower than 65％.The eGFRs were underestimated by formulas evaluated by PENIA in CKD stage 1.All the eGFRs were overestimated remarkably by all equations in CKD stage 5.Conclusions None of the eight Cys C based formulas are ideal for estimation of GFR in Chinese CKD patients,and they can not be applied to Chinese patients directly.For this patient population,further studies will be needed to develop a more accurate Cys C-based GFR estimation formula that includes ethnicity,age and other factors.

Objective To evaluate the clinical performance of INNOVANCE D-Dimer,and provide information for clinical application.Methods 402 cases of sodium citrate anticoagulant blood were tested with INNOVANCE assay and PLUS assay on CA7000 analyzer to measure plasma D-Dimer levels.VIDAS-30 immunology analyzer was also used to validate the two assays.4 patients with elevated D-Dimer were monitored continuously during 5 days using INNOVANCE assay and PLUS assay respectively,then the consistency of trend between 2 assays was analyzed.Plasma specimens added with hemoglobin,bilimbin and triglyceride were used to verify the anti-interference capability of INNOVANCE D-Dimer assay.Results In 402 specimens,the result ranges of INNOVANCE D-Dimer and PLUS D-Dimer were [2.15 (0.33,8.63)]mg/L FEU and [325.50 (123.75,974.00)] μ,g/L DDU,respectively.The consistency between two assays was poor (Z =-17.375,P =0.000),especially the results in the range of PLUS D-Dimer (201-300) μg/L DDU and (301-400) μg/L DDU,the coincidence rates were only 25％ and 15％,respectively; the coincidence rate was up to 85％ during PLUS D-Dimer (500-600) μg/L DDU; the coincidence rate was close to 100％ when PLUS D-Dimer over 700 μg/L DDU.Totally 47 of 402 cases were unmatched between two assays.Verified by VIDAS 30,83.0％ (39/47) was false negative for PLUS assay,4.3％ (2/47) was false negative for INNOVANCE assay,12.7％ (6/47) was false positive for PLUS assay.There were 5 false positives and 39 false negative for PLUS assay,totally 45 cases; Two false negative for INNOVANCE assay.Four patients with elevated D-Dimer were monitored and the results showed similar trend between 2 assays.For INNOVANCE assay,the capacity of anti-interference to free bilirubin,unconjugated bilirubin,hemoglobin,and triglyceride was up to 217 μmol/L,337 μmol/L,41.04 g/L,18.35 mmol/L,respectively.Conclusions INNOVANCE assay can markedly reduce false negative results of D-Dimer compared with PLUS assay.INNOVANCE D-Dimer has good performance on anti-interference to jaundice,hemolysis and lipemia samples.

Objective To validate the analytical performance of three Cys C reagents with particle-enhanced turbidimetric immunoassay(PETIA) method used on the automatic biochemistry analyzer for preliminary clinical application.Methods The performance of three Cys C reagents (labeled as A, B, C) with PETIA method from Shanghai Jing Yuan Co., Beijing Leadman Co. and Beijing Jiuqiang Co. on OlympusAU2700 automatic biochemistry analyzer were assessed.According to the standard of CLSI EP6-A, EP15-A and EP7-P, the precision, linearity range, disturbance (bilirubin, hemoglobin, chyle) were assessed, and compared with those of Cys C reagent based on particle-enhanced nephelometric immunoassay(PENIA) from Dade Behring Co.. The reference ranges for Cys C in serum of 120 healthy individual were evaluated.Results The within-run CVs of the three reagents (A, B and C) were 3.08%-3.2%, 2.3%-4.15% and 1.38%-1.53% respectively.The total CV in A, B and C were 3.29%-3.44%, 2.65%-5.18% and 1.67%-1.69% respectively, lower than the stated.Limits of quantitative determination (LOQ) of the three reagents were 0.41, 0.23 and 0.07 mg/L, basically meeting the testing requirement.The linearity range was 0.22-7.26 mg/L(r=0.996), 0.20-7.72 mg/L(r=0.999)and 0.20-7.62 mg/L(r=0.997)in the three reagents, which demonstrated a sound linear correlation. For interference tests, no remarkable interference (<±10%) of reagent C was detected when bilirubin≤684 μmol/L, hemoglobin≤9.7 g/L and Chyle turbidity≤6 200 FTU; and no significant interference of reagent B was found when bilirubin≤684 μmol/L, hemoglobin≤6.79 g/L and Chyle turbidity≤6 200 FTU; when bilirubin≤684 μmol/L, hemoglobin≤4.85 g/L and Chyle turbidity≤1 240 FTU reagent A was not interfered significantly. The comparison afte and before the high-speed centrifugation reveals that the average percentage of bias for reagents A, B, C measured Cys C in chylous serum samples of patients was -8.31%, 1.52%, 1.32%, respectively.In method comparison tests, the regression equations of the three reagents compared with Dade Behring PENIA Cys C reagent were as follows:Y=0.787X+0.492 (R2=0.976), Y=1.098X+0.137 (R2=0.982) and Y=1.037X+0.249 (R2=0.996), respectively. Agreement rates of the high Cys C in reagent A, B, C and Dade Behring Cys C reagent were 80% (Kappa=0.615,P=0.000), 100% (Kappa=1.000,P=0.000), 91.2% (Kappa=0.824,P=0.000); While for reference range of preliminary clinical assessment, diagnosis coincidence rate of reagent A increased to 98.8% (Kappa=0.974,P=0.000). Conclusions When used in automatic biochemical analyzer, the three Cys C reagent with PETIA showed high precision,sensitivity, and sound correlation with Dade Behring PENIA reagents.The three reagents are all able to meet clinical test requirements, nevertheless, anti-interference capability were diffierent and the reference range should be further validated.

Objective To validate the four chronic kidney disease epidemiology collaboration (CKD-EPI) predictive equations based on serum creatinine (SCr) and cystatin C (Cys C) in Chinese CKD patients,and try to develop the GFR predictive equations for Chinese CKD patients.Methods254 CKD patients were randomly selected from four Grade ⅢA hospitals in different regions in China from September 2007 to December 2010.Clearance of dual plasma sampling 99mTc-DTPA was used to measure glomerular filtration rate (rGFR) in 254 CKD patients.The serum concentration of Cr and Cys C were measured.CKD-EPI SCr equation,Cys C equation,Cys C equation adjusted for age,sex and race,SCr/Cys C combinated equation adjusted for age,sex and race were used to estimate GRF ( labeled as eGFR1,eGFR2,eGFR3 and eGFR4,respectively).The correlation,bias and precision of eGFRs were compared with rGFR by Wilcoxon signed rank test,intraclass correlation coefficient (ICC) and Spearman correlation analysis.The deviation degree between rGFR and different eGFRs was compared via Bland-Altman graph.The accuracy within 15％,25％,30％ ( P15,P25,P30) and the staging correctness of eGFR against CKD at different stages was calculated.ResultsThe rGFR in 254 CKD participants was [ 48.07 (26.19 -92.97 )] ml · min -1·(1.73 m2) -1.The Spearman correlatiou coefficients (CC) of eGFR and rGFR varied within the range of 0.873 - 0.896 ( P =0.000 ).The intra-class CC ( ICC ) varied within the range of 0.920 - 0.942.The correlation of eGFR4 was the best.The absolute deviations of 4 eGFRs and deviation precision were eGFR4 ＜eGFR3 ＜ eGFR2 ＜ eGFR1.The 95％ confidence intervals for the regression line of 4 eGFRs shown by Bland-Altman graphs were 92.5,87.3,83.0 and 76.1 ml · min-1 · ( 1.73 m2 ) -1,respectively,with the best result of eGFR4.For P30,the correctness of 4 eGFRs were eGFR4 ＞ eGFR3 ＞ eGFR2 ＞ eGFR1,but no significant difference was found by Chi square test (x2 =6.448,P =0.092).The overall correctness rate in 4 eGFRs against CKD stages were 48.4％ -57.5％,with the highest consistency of eGFR4,but their staging correctnessratewerenotideal(Kappa values were 0.405,0.348,0.366 and 0.463,respectively).Conclusions Compared with CKD-EPI SCr equation,no advantage was found in CKD-EPI Cys C equation.The Cys C equation adjusted by age and sex shows a little advantages over CKD-EPI Cys C equation in bias,precision,correlation and accuracy.The CKD-EPI SCr/Cys C combinated equation adjusted by age,sex and race has advantage over other three equations not only in bias,precision,correlation and accuracy,but also in staging correctness.However,the validation of this equation is still not fairly ideal for Chinese CKD patients.Based on these findings,it is essential for the Chinese CKD patients to develop SCr/Cys C combined predictive equation which adjusted by age,sex or other factors.(Chin J Lab Med,2012,35:798-804)

ObjectiveTo investigate the impacts of different serum creatinine detection methods,including Jaffe and enzymatic methods,on the efficacy of different GFR estimation equations in CKD patients in China.MethodsrGFR of 176 patients with CKD were determined by dual plasma sample method 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) plasma clearance rate.Serum creatinine was detected with four kinds of creatinine reagents from different manufacturers.Cockcroft-Gault Equation corrected for body surface area (CG/BSA),simplified Modification of Diet in Renal Disease (MDRD) Study equation,IDMS-traceable MDRD equation,CKD epidemiology collaborative research (CKD-EPI) equation and two Chinese simplified MDRD equation (project group equation 1,2) were applied to calculate estimated GFR (eGFR)respectively.eGFRwerecomparedwithrGFRforthecorrelation, deviation, precisionand30％ accuracy.ResultsThe mean rGFR of 176 patients with CKD,was [ 40.70 ( 19.41 -84.35 ) ] ml · min- 1 ·( 1.73 m2 ) -1.For all GFR estimation equations,there were significant differences in eGFR results between enzymatic method and Jaffe method,when analyzed by the Wilcoxon signed-rank test.eGFR results assessed by two enzymatic creatinine detection systems showed no significant difference,while eGFR results analyzed by two Jaffe detection system were significantly different.The intraclass correlation coefficient (ICC) of eGFR and rGFR ranged from 0.879 to 0.923 by Jaffe method,while from 0.925 to 0.946 by enzymatic creatinine method.ICC and Pearson correlation analysis revealed a significant correlation between eGFR and rGFR,and the correlation was better when using enzymatic method.Bland-Altman plots indicated that large deviation occurred in the high value area of GFR using various equations.However,deviation with the enzymatic creatinine method was smaller than that with the Jaffe method. When rGFR ≥ 60 ml · min- 1 ·(1.73 m2) -1,the 30％ accuracy of eGFR using enzymatic creatinine method for all six equations was between 68.3％ and 90.0％,while it was between 41％ and 75％ when using Jaffe method. The 30％ accuracy of eGFR using enzymatic creatinine method was significantly higher than that using picric acid method for these equations except for the project group equation 1.When rGFR ＜60 ml · min -1 · ( 1.73 m2 ) -1,the 30％accuracy of eGFR using both methods was between 39.7％ -49.1％,40.5％ -52.6％respectively,and the difference of data showed no statistical significance.For the same equation,there was a significant differernce in 30％ accuracy of eGFR between two enzymatic creatinine detection systems,while there was no significant differernce between two Jaffe creatinine detection systems.ConclusionsA significant difference was demonstrated in the same GFR evaluation equation using two different creatinine detection methods (Jaffe method and enzymatic method).The correlation between rGFR and eGFR,the degree of deviation,and accuracy of eGFR results assessed by enzymatic creatinine method were better than those by Jaffe method.The eGFR results assessed by different enzymatic detection systems revealed no significant difference.

Objective:To establish the clot waveform analysis (CWA) reference intervals of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg) and thrombin time (TT) parameters CT, |Min1|, |Min2|, |Max2| and observe the changes in patients with coagulation factors deficiency.Methods:One hundered and twenty-five cases of apparent healthy person were enrolled to establish the CWA reference intervals of four coagulation parameters and 25 cases with coagulation factors were used to study the changes of CWA patients.Results:The CWA reference intervals of PT |Min1| (dT/dt), |Min2| (d 2T/dt 2), |Max2| (d 2T/dt 2) are3.14±1.22, 0.56±0.22 and 0.50±0.18; The CWA reference intervals of APTT |Min1| (dT/dt), |Min2| (d 2T/dt 2), |Max2| (d 2T/dt 2) are 4.75±1.71, 0.78±0.29 and 0.65±0.28; The CWA reference intervals of Fbg CT(s), |Min1| (dT/dt), |Max2|(d 2T/dt 2) are 7.01±1.96, 1.22±0.51 and 0.15±0.11; The CWA reference intervals of TT |Min1| (dT/dt), |Min2| (d 2T/dt 2), |Max2| (d 2T/dt 2) are 0.95±0.32, 0.14±0.05 and 0.07±0.03.These parameters of CWA in factor Ⅴ deficient patients were significantly reduced, the activity of coagulation factor Ⅶ was 0.42, |Min2| and |Max2| were significantly lower than that of normal people. The paramenters of CWA in factor Ⅶ deficient patients were significantly reduce. Conclusion:The CWA reference intervals of four CWA parameters helps judgment of coagulation factor deficiency.

Objective To establish hemolysis-icterus-lipemia(HIL)alert indices and allowable ranges of sample volume check in CS5100 and CN6000 automated coagulation analyzers.Methods The samples of interference substances were prepared by using the interference reagent kit or obtained through artificial freeze and suction.Twenty-one samples with various concentrations of interference substances were used to evaluate repeatability of HIL indices,and 206 such samples were used to evaluate the consistency of HIL indi-ces between two different instrument systems.A total of 425 specimens were collected to evaluate the concentration distribution of inter-fering substances with various HIL indices,and 378 specimens were used to evaluate the consistency of HIL indices between manual assessment and instrumental operation.Six coagulation screening tests were analyzed parallelly for the samples prepared with the artifi-cial interference before and after,and the HIL indices were recorded.The differences between the paired samples with different concen-trations of interference substances were compared,and the HIL alert indices in different detection intervals of each test were deter-mined.Ten tubes of samples with standard volume±10％lower and upper limits were prepared using distilled water to establish the al-lowable range of volume check for each instrument,and 2 933 samples were used to validate the established ranges.Results The re-peatabilities of the HIL indices in the two systems were favorable,and the consistency between the two systems was fine(Kappa values were 0.969,0.978 and 0.991,respectively,P=0.000).The consistency between instrumental and manual assessment for the evalua-tion of hemolytic samples was just average level(Kappa values were 0.421 to 0.702,P＜0.001).The consistency for jaundice samples between instrumental and manual assessment was poor(Kappa values were 0.023 to 0.267),except the P=0.258 between the operator 1 and instrument,all the other operators were remaining P＜0.001.The consistency between instrumental and manual assessment for chyle samples was better(Kappa values 0.559 to 0.838,P＜0.001).The HIL alert indices varied with different intervals of detection for each test.The APTT H alert index was significantly lower than that measured in other tests when ordinary heparin was used in anti-co-agulation monitoring.The allowable ranges of volume check in 5 coagulation analyzers were 41.0 to 55.5 mm,44.3 to 58.4 mm,41.3 to 56.2 mm,58.3 to 72.5 mm and 59.2 to 73.3 mm respectively.Conclusion The HIL alert indices and allowable range of volume check were determined preliminarily for coagulation screening tests in various detection intervals of two different systems in our laboratory,which provided the basis for achieving intelligent management of pre-analytical quality control.

Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.