|Year : 2014 | Volume
| Issue : 1 | Page : 20-23
Comparison of seven kinds of calculation methods on glomerular filtration rate in patients with chronic kidney disease
Xiaoguang Zhang, Gang Yu, Niansong Wang, Qing Xue, Xiaohua Sheng, Yan Yan
Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
|Date of Web Publication||25-Jul-2014|
Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233
Source of Support: None, Conflict of Interest: None
Objective: The objective was to compare the diagnostic value of seven kinds of calculation methods on glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD). Materials and Methods: A total of 120 cases with CKD and 120 normal people were included in this study. They were grouped according to the GFR results estimated by the plasma clearance of 99m technetium-diethylene-triamine-pentaacetate. Serum cystatin C (Cys C) concentrations were detected by enzyme-linked immunosorbent assay. GFR and serum creatinine (SCr) was simultaneously analyzed using Automatic Biochemistry Analyzer. Estimated GFR (eGFR) was detected with seven kinds of calculation methods. Results: Modification of diet in renal disease (MDRD) equations obtained significantly lower GFR in group CKD2, while Cockcroft-Gault (CG) equation obtained significantly lower GFR in group CKD3. There were no statistical differences between four Cys C-based equations (GFR estimated via cystatin [Cys-eGFR] formula) and GFR from CKD1 to CKD5. In the groups CKD2 and CKD3, GFRs detected by four kinds of formula Cys-eGFR were all superior to that by CG and MDRD. For the CKD patients with GFR <60 mL/min/1.73 m 2 , four kinds of receiver operating characteristic (ROC) curve area of Cys-eGFR were more than GFR estimated via creatinine (Cr-eGFR) formula, the differences were statistically significant. For those with GFR <30 mL/min/1.73 m 2 , the comparative results of ROC curve area had no statistical difference. Conclusion: Cys-eGFR is a more accurate equation for estimating GFR than CG and MDRD equation, but not superior to Cr-eGFR, which based on SCr in advanced chronic renal failure patients.
Keywords: Chronic kidney disease, Cockcroft-Gault equation, cystatin C-based equations, glomerular filtration rate estimation equation, modification of diet in renal disease equation
|How to cite this article:|
Zhang X, Yu G, Wang N, Xue Q, Sheng X, Yan Y. Comparison of seven kinds of calculation methods on glomerular filtration rate in patients with chronic kidney disease. J Integr Nephrol Androl 2014;1:20-3
|How to cite this URL:|
Zhang X, Yu G, Wang N, Xue Q, Sheng X, Yan Y. Comparison of seven kinds of calculation methods on glomerular filtration rate in patients with chronic kidney disease. J Integr Nephrol Androl [serial online] 2014 [cited 2020 Feb 26];1:20-3. Available from: http://www.journal-ina.com/text.asp?2014/1/1/20/137547
| Introduction|| |
Patients with chronic kidney disease (CKD) have accounted for 7-10%  in the population of the whole word. The CKD prevalence rate is approximately 11%  in the adults of the United States, while that is 18.7% in Beijing population according to the survey.  The accurate assessment of patient's renal function is critical to the diagnosis and appropriate staging of CKD. Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines point out that only serum creatinine (SCr) could not be used for assessment of renal function and prediction equation should be used clinically to estimate glomerular filtration rate (GFR) and also recommend to apply both modification of diet in renal disease (MDRD) and Cockcroft-Gault (CG) equations to calculate the GFR in adults.  CG equation is subject to the influence of age and body weight and shows large error in the old patients, and body weight is also an important contributor to the inaccuracy of this equation.  The underestimation of patients with high GFR or normal GFR by MDRD equation leads to the inaccuracy.  Therefore, we need a new prediction equation to calculate GFR in clinic and cystatin C (Cys C) is regarded as a more sensitive index than SCr when assessing mild renal dysfunction. Four GFR estimated via cystatin (Cys-eGFR) formula equations for estimated GFR (eGFR) were introduced based on Cys C. In this study, we compared the eGFRs obtained through MDRD equation, simplified MDRD equation, CG equation and four Cys equations by taking 99m technetium-diethylene-triamine-pentaacetate ( 99m Tc-DTPA) plasma clearance, which dual-plasma-sample method as reference standard.
| Materials and methods|| |
A total of 120 patients hospitalized in our hospital from December 2006 to December 2008 were enrolled in this study. All these patients met K/DOQI guidelines for CKD diagnosis criteria without hyperthyroidism history and did not receive hormone therapy. Among these patients, there were 68 males and 52 females with age ranges 22-85 years (average 55.1 ± 15.85 years). Fifty-seven cases were diagnosed as chronic glomerulonephritis, 30 cases as diabetic nephropathy, 25 cases as hypertensive renal arteriolar sclerosis, 4 cases as lupus nephritis, 2 cases as chronic pyelonephritis, 1 case as vasculitis, and 1 case as obstructive nephropathy. They were divided into five groups according to K/DOQI guidelines for CKD staging:  21 cases in group CKD1, 23 cases in group CKD2, 24 cases in group CKD3, 24 cases in group CKD4, and 28 cases in group CKD5. Other 120 patients with average age (53.1 ± 12.5) years, who had no history of nephropathy, hypertension, and diabetes mellitus and showed normal results in both urine test and renal function, were selected as controls.
Method of detection
Detection of standard glomerular filtration rate
Glomerular filtration rate was detected using 99m Tc-DTPA plasma clearance (GFR) by dual-plasma-sample method in the Department of Nuclear Medicine of our hospital.
Detection of serum cystatin C
Serum Cys C was detected by enzyme-linked immunosorbent assay, strictly accorded to the instructions. Reagent kit was purchased from Shanghai Debo Biotechnology Co., Ltd. Biochemical indexes such as SCr and albumin were detected in the Department of Laboratory Medicine of our hospital using Automatic Biochemistry Analyzer.
Calculation of estimated glomerular filtration rate with seven prediction equations
(1) CG equation: Creatinine clearance rate (CCr) (mL/min) obtained through this equation was multiplied by 0.84. GFR was obtained and standardized by body surface area (BSA), that is, CG-eGFR: CCr = [(140-age) × body weight (kg) × (0.85, female)]/(72 × SCr), CG-eGFR = CCr × 0.84 × 1.73/BSA. BSA was calculated with DuBois equation: BSA (m 2 ) = 0.007184 × body weight (kg) 0.425 × height (cm) 0.725 ; (2) simplified MDRD equation = 186 × (SCr)−1.154 × (age)−0.203 × (0.742, female); (3) MDRD equation = 170 × (SCr)−0.999 × (age)−0.176 × (blood urea nitrogen)−0.170 × albumin 0.818 × (0.762). The above SCr was in mg/dL; age in year(s); weight in kg; (4) Cys-eGFR (Arnal-Dade) = 74.835/(Cys C 1.333 ); , (5) Cys-eGFR (Rule) = 66.8 × (CysC)−1.30 ;  (6) Cys-eGFR (MacIsaac) = (84.6/Cys C)-0.2;  (7) Cys-eGFR (Tan) = (87.1/Cys C)-6.87. 
Statistical software SPSS 11.5 was used, measurement data was expressed as x- ± s, paired t-test was used to compare the estimated value and reference value of GFR, and two sets of independent-sample t-test were applied to compare eGFR and normal controls. Pearson's correlation coefficient was used to measure the correlation between GFR estimated value and reference value; the area under curve of different prediction equations was calculated by using area under the receiver operating characteristic (ROC) curve. Differences were considered to be statistically significant when P < 0.05.
| Results|| |
Comparison of determination results of patients in different stages of chronic kidney disease
There were statistical differences when we compared eGFR obtained by each individual equation and that of normal controls in groups CKD2 to CKD5. The value of GFR obtained by MDRD equation was statistical different compared with that by simplified MDRD equation in group CKD2. Statistical differences were seen when we compared GFRs detected by CG equation in group CKD3; However, there were no statistical differences of GFRs between four Cys C-based equations in groups CKD1 to CKD5 [Table 1].
|Table 1: Comparison of determination results of patients in different stages of CKD (x− ± s)|
Click here to view
Analysis of correlation between estimated glomerular filtration rate obtained through different equations and isotope glomerular filtration rate
The correlations between Cys-eGFRs obtained by four equations and GFR were all superior to those of CG and MDRD equations in groups CKD2 and CKD3, whereas in groups CKD1, CKD4, and CKD5, all measurement results showed similar correlation between GFR and isotope GFR [Table 2].
|Table 2: Correlation between eGFR obtained through different equations and isotope GFR in different CKD groups (expressed as r)|
Click here to view
The areas under ROC curve calculated by four Cys-eGFR equations were statistically significant larger than that of Cr-eGFR equation in CKD patients with GFR <60 mL/min/1.73 m 2 ; but no statistically significant differences was observed in the areas under ROC curve of CKD patients with GFR <30 mL/min/1.73 m 2 [Table 3].
|Table 3: Comparison of AUCROC calculated by seven equations when GFR <60 mL/min/1.73 m2/sup> (1) and GFR <30 mL/min/1.73 m2 (2)|
Click here to view
| Discussion|| |
Glomerular filtration rate is an index of assessment of renal function which is very important for diagnosis, appropriate staging and treatment of CKD. K/DOQI guidelines point out that prediction equation should be used to estimate eGFR in clinic. Currently, MDRD and CG equations are two internationally acceptable methods for calculating GFR (or eGFR). These two equations are both based on the measurement of SCr. For CG equation, CCr is calculated by detecting 24 h urine Cr of 249 CKD patients (96% male) with average age of 18-92 years and SCr of 87 5-157 4 μmol/L, thus a regression equation is obtained by this "gold standard."  Whereas, most studies now consider that this equation is not reliable since it is obtained mostly in patients with normal renal functions and its accuracy may be compromised in patients with renal insufficiency. MDRD equation is based on MDRD: A total of 1628 patients (983 males, 1304 Caucasians) with average GFR of 39.8 mL/min are summarized, and this equation is established using 1070 cases and confirmed by the remaining 558 cases. Study conducted by Levey et al.  shows that MDRD is superior to CG in terms of predicting GFR, while some studies consider that GFR is underestimated by MDRD.  It remains controversial that MDRD is applicable to all population since it is almost obtained from patients with renal diseases. And data for establishing MDRD is dominantly derived from white people rather than black people.
Cystatin C was discovered firstly in cerebrospinal fluid in 1961. Having low molecular weight and carries positive charge, Cys C can freely penetrate glomerular basement membrane and be absorbed and metabolized completely by renal proximal convoluted tubular as well as no tubular secretion. It is generated at a constant rate in tissues, and its excretion is influenced by GFR only rather than other factors such as sex, age, diet, inflammation, infection, blood lipid, and hepatic diseases. Most studies consider that Cys C is a more sensitive index than SCr with regard to the assessment of mild renal dysfunction. , In our study, we compared the eGFRs obtained by MDRD, simplified MDRD, CG and four Cys equations by taking 99m Tc-DTPA plasma clearance (GFR) by dual-plasma-sample method as reference standard. The study indicated that the correlation between Cys-eGFR and isotope GFR was significantly superior to that of CG and MDRD in groups CKD1 and CKD2; no statistical difference was observed in the correlation between seven equations and GFR in groups CKD3, CKD4, CKD5, and CKD7. In group CKD2, the measurement results of MDRD and the simplified MDRD could not reflect the changes of GFR accurately; in group CKD3, there was statistical difference between CG-eGFR and GFR, but no statistical difference was observed in Cys-eGFR compared with GFR through group CKD1 to CKD5. This demonstrated that the results of CG and MDRD equations could better reflect the value of GFR in groups CKD1, CKD4, and CKD5 than that in groups CKD2 and CKD3. In addition, ROC curve denotes the relationship between sensitivity and specific degree and is usually used to compare the value of two or more diagnosis tests. The larger area under ROC curve is, the higher diagnostic accuracy is. The areas under ROC curve calculated by four Cys-eGFR equations were statistically significant larger than that of Cr-eGFR equation in CKD patients with GFR <60 mL/min/1.73 m 2 ; but no statistically significant differences was observed in the areas under ROC curve of CKD patients with GFR <30 mL/min/1.73 m 2 .
| Conclusion|| |
Glomerular filtration rate estimated via cystatin equation is more reliable than Cr-eGFR in mild to moderate CKD patients combined with renal insufficiency, and the diagnosis values of these equations are similar in advanced chronic renal failure patients. The sample size should be further expanded to determine the value of Cys-eGFR equation in evaluation of GFR of CKD patients and to provide more basis for clinical diagnosis.
| Acknowledgments|| |
The research is supported by grant 81270824 from the Project of National Nature Science Foundation of China, Shanghai Science and Technology Project (11DZ1921904; 11410708500). The funders had no role in study design, data collection and analysis, decision to publish and preparation of the manuscript.
| References|| |
|1.||Zoccali C. Traditional and emerging cardiovascular and renal risk factors: An epidemiologic perspective. Kidney Int 2006;70:26-33. |
|2.||Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria and renal insufficiency prevalence guides population screening: Results from the NHANES III. Kidney Int 2002;61:2165-75. |
|3.||Zhang Lu-xia, Zuo Li, Xu Guo-bin, Wang Fang, Wang Shu-yu, Wang Mei, et al. Epidemiological Research Center for chronic kidney disease among elderly population in Shijingshan District, Beijing. Chin J Nephrol 2006;22:67-71. |
|4.||National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266. |
|5.||Rigalleau V, Lasseur C, Perlemoine C, Barthe N, Raffaitin C, Chauveau P, et al. Cockcroft-Gault formula is biased by body weight in diabetic patients with renal impairment. Metabolism 2006;55:108-12. |
|6.||Ibrahim H, Mondress M, Tello A, Fan Y, Koopmeiners J, Thomas W. An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes. J Am Soc Nephrol 2005;16:1051-60. |
|7.||Thomas L, Huber AR. Renal function - Estimation of glomerular filtration rate. Clin Chem Lab Med 2006;44:1295-302. |
|8.||Dade Behring. Increase Sensitivity and Reliability in Renal Function Analysis. Marburg, Germany: Dade Behring; 2005. |
|9.||Rule AD, Bergstralh EJ, Slezak JM, Bergert J, Larson TS. Glomerular filtration rate estimated by cystatin C among different clinical presentations. Kidney Int 2006;69:399-405. |
|10.||Macisaac RJ, Tsalamandris C, Thomas MC, Premaratne E, Panagiotopoulos S, Smith TJ, et al. Estimating glomerular filtration rate in diabetes: A comparison of cystatin-C- and creatinine-based methods. Diabetologia 2006;49:1686-9. |
|11.||Tan GD, Lewis AV, James TJ, Altmann P, Taylor RP, Levy JC. Clinical usefulness of cystatin C for the estimation of glomerular filtration rate in type 1 diabetes: Reproducibility and accuracy compared with standard measures and iohexol clearance. Diabetes Care 2002;25:2004-9. |
|12.||Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41. |
|13.||Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-70. |
|14.||Lin J, Knight EL, Hogan ML, Singh AK. A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 2003;14:2573-80. |
|15.||Cepeda FJ, Fernández E, Pobes A, Baños LM. Utility of cystatin-C in hospitalized patients. Comparing with different methods of assessing renal function. Nefrologia 2007;27:168-74. |
|16.||Yang YS, Peng CH, Lin CK, Wang CP, Huang CN. Use of serum cystatin C to detect early decline of glomerular filtration rate in type 2 diabetes. Intern Med 2007;46:801-6. |
[Table 1], [Table 2], [Table 3]