The Study Of CKD-EPI Equation Employed ^99mTc-DTPA Dual Plasma Sample Clearance Method As The Reference Method

Part I99mTc-DTPA renal dynamic imaging method may be unsuitable as the reference method in investigating the validity of CKD-EPI equation for determining glomerular filtration rateObjective: Glomerular filtration rate(GFR), the best overall index of renal function in health and disease, can be evaluated by several approaches.Recently, a new serum creatinine-based equation was reported by the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI), which was developed based on a large data set pooled from research and clinical populations, including renal disease patients and healthy individuals. The validity of this equation was widely investigated and the results indicated that CKD-EPI equation performed well with less bias and greater accuracy than the Modification of Diet in Renal Disease(MDRD) equation. Although the renal dynamic imaging method has been employed as the gold standard in a few studies on assessing the performance of CKD-EPI equation, little is known about whether renal dynamic imaging method is more accurate than CKD-EPI equation in determining GFR. So the aim of our study was to compare the measurements of GFR determined by 99 m Tc-diethylene triamine pentaacetic acid(99m Tc-DTPA) renal dynamic imaging with those estimated by Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) equation and to identify a more accurate measurement of GFR of chronic kidney disease(CKD) in clinical practice.Method: The GFR was determined simultaneously by 3 methods:(a)CKD-EPI equation(e GFRckd-epi);(b) renal dynamic imaging method(d GFR);(c) dual plasma sample clearance method(r GFR). And the r GFR was employed as the reference method. The correlation, regression, and limit of agreement of d GFR and e GFRckd-epi were used to demonstrate the validity ofthe two methods. What’s more, the comparison of bias, precision, accuracy between d GFR and e GFRckd-epi was analyzed to identify the most suitable method. The analysis of bias, precision and accuracy was repeated after stratifying patients by a measured r GFR cutpoint of 60 ml·min-1·(1.73m2)-1.Results: A total of 149 patients were enrolled(78 females with an age range 18-73 y(mean: 46 y) and 71 males with an age range 20-77 y(mean: 48y)). Both d GFR and e GFRckd-epi correlated well with r GFR and the regression equation of d GFR and e GFRckd-epi against r GFR was Y=2.462+0.914X(r=0.909; RMSE=15.123 ml/min/1.73m2; P<0.001) and Y=-4.289+0.962X(r=0.919; RMSE=14.323 ml/min/1.73m2; P<0.001)respectively. The correlation coefficient of the two methods was not different significantly. In addition, Bland-Altman analysis showed preferable agreement between the two methods and the reference method. In the whole cohort, the mean bias of d GFR and e GFRckd-epi was 6.85 ml/min/1.73m2 and 3.31ml/min/1.73m2, and the comparison showed significant difference in the performance of bias(t= 3.191, P=0.002). Although 15% and 30% accuracy of e GFRckd-epis were not higher than that of d GFR(48.99% vs 41.61% for 15%accuracy, P=0.207; 64.44% vs 71.14% for 30% accuracy P=0.282),e GFRckd-epi made some improvement in 50% accuracy over d GFR(91.28%vs 83.22%; P= 0.05). And the precision of e GFRckd-epi was not significantly lower than that of d GFR(14.34 ml/min/1.73 m2vs15.39 ml/min/1.73 m2;F=1.152, P=0.831). The performance of bias, precision and accuracy in the lower-GFR subgroup was almost completely consistent with that in whole cohort, whereas the difference of those indexes in the higher-GFR subgroup did not reach significance.Conclusions: Although both CKD-EPI equation and renal dynamic imaging can be used in determining glomerular filtration rate of chronic kidney disease patients, CKD-EPI equation is more accurate than renal dynamic imaging. As a result, 99 m Tc-DTPA renal dynamic imaging may be unsuitable as the reference method in investigating the validity of CKD-EPI equation. But limited data can prove which one is more precise in the GFR>60ml/min/1.73 m2 subgroup.Part II A comparison between CKD-EPI equation and other three equations based on Serum creatinineObjectives: Chronic kidney disease(CKD) is a worldwide public health problem that can lead to serious outcomes and the incidence is arising year by year. The glomerular filtration rate(GFR) is a primary index of kidney function, which can be extremely useful in diagnosing, staging, assessing the response to treatment and appraising the prognosis. The gold standard for predicting GFR is insulin clearance, but the widespread application was limited because of the complexity and time-consuming procedure. Because of the limited accuracy of current equations based on serum creatinine, the Chronic Kidney Disease Epidemiology Colaboration(CKD-EPI) developed a new equation named CKD-EPI equation. So the aim of this study was to compare the performance of the CKD-EPI equation, the modified Modification of Diet in Renal Disease(m MDRD) equation,Cockroft-Gault(C-G) formula, the abbreviated Modification of Diet in Renal Disease(a MDRD) equation in determining glomerular filtration rate in Chinese patients with chronic kidney disease, and detect the most proper method to measure GFR in clinical practice.Methods: 99 m Tc-diethylene triamine pentaacetic acid(99m Tc-DTPA)plasma clearance method measured by dual plasma sampling method was considered as the reference standard(r GFR). GFR were estimated simultaneously using four methods:(1) CKD-EPI equation(e GFR1);(2)m MDRD equation(e GFR2);(3) C-G formula(e GFR3);(4) abbreviated MDRD equation(e GFR4). The comparison of correlation, regression, bias,precision, accuracy, limit of agreement and receiver-operating characteristics(ROC) for detecting CKD(with cut-off 60 ml/min/1.73m2) among the methods was analyzed to identify the most suitable method.Results: 154 patients with CKD were enrolled in the present study. The average of r GFR was 56.50±36.24(ranging from 4.17 to 150.24)ml/min/1.73m2. The average GFR evaluated by the five equations was e GFR158.90±35.83(P=0.036);e GFR2 55.83±30.26(P=0.603); e GFR3 60.60±43.61(P=0.134) and e GFR4 57.44±24.68(P=0.604) ml/min/1.73m2 respectively.All the equations correlated well with r GFR and the correlation coefficient of CKD-EPI equation was the highest(r =0.922, P<0.001). In the overall performance, the CKD-EPI equation represented the best capability in precision and 30% accuracy. And its performance on bias showed no significant difference statically compared with other four equations. The area under the ROC curves of e GFR1,e GFR2,e GFR3 and e GFR4 was0.964(0.936,0.992)、0.960(0.934, 0.986)、0.918(0.878, 0.956) and 0.911(0.867,0.955) respectively. The Bland-Altman analysis showed that the 95% limit of agreement for CKD-EPI equation was-25.5 to 30.3 ml/min/1.73m2, which was the least range among the tested equations.Conclusions: Although its bias did not overmatch the other three equations in our patient group, the CKD-EPI equation outperformed the other equations based on creatinine in precision, 30%accuracy and 95% limit of agreement, and it is very simple, time-saving, and cost-effective. So we recommend intensely the CKD-EPI equation should be the most suitable method in determining GFR in Chinese patients with CKD and can be applied generally in clinical practice.Part III The modified CKD-EPI equation may be not more accurate than CKD-EPI equation in determining glomerular filtration rate in Chinese patients with chronic kidney diseaseObjectives: To investigate the application of the new modified Chronic Kidney Disease Epidemiology Collaboration(m CKD-EPI) equation developed by Liu in the measurement of glomerular filtration rate(GFR) in Chinese patients with Chronic Kidney Disease(CKD) and to evaluate whether the modified one is more accurate than the original one in clinical practice.Methods: The GFR was determined simultaneously by 3 methods:(a)CKD-EPI equation(e GFRckd-epi);(b) modified CKD-EPI equation(e GFRmodified);(c)99mTc-diethylene triamine pentaacetic acid(99mTc-DTPA)dual plasma sample clearance method(r GFR). GFR evaluated by 99 m Tc-DTPAdual plasma sample clearance method(r GFR) was employed as the reference standard. The correlation coefficient and regression were used to demonstrate the validity of the two methods. The comparison of bias, precision and accuracy were analyzed to identify which equation showed better performance in determining GFR.Results: A total of 170 patients were enrolled. Both e GFRckd-epickdepi and e GFRckd-epimodified were correlated well with r GFR(correlation coefficient was 0.907 and 0.868, respectively) and the regression equation was r GFR =3.13+0.976 e GFRckd-epi(F=782.23; P<0.001) and r GFR =-35.73+1.532 e GFRckd-epimodified(F=515.29; P<0.001). In terms of comparison,the results revealed that e GFRmodified, compared with e GFRckd-epi, showed worse performance on bias, precision and 30% accuracy in the whole cohort(-2.02 VS 3.14 ml/min/1.73m2 for bias, t=4.095,P<0.001; 15.51 VS 21.38ml/min/1.73m2 for precision, F=24.808, P<0.001; 72.35% VS 48.24% for±30% accuracy,P<0.001).Conclusions: The new modified CKD-EPI equation can not replace the original CKD-EPI equation in determining glomerular filtration rate in Chinese patients with chronic kidney disease, and the original one remains the optimal choice.