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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 14  |  Issue : 3  |  Page : 230-234

Correlation of methods of glomerular filtration rate estimation: Cockcroft–gault equation, modification of diet in renal disease, chronic kidney disease epidemiology collaboration, and DTPA renography in prospective renal donors -a retrospective analytical study


Department of Urology and Renal Transplant, Mahatma Gandhi Medical College, Jaipur, Rajasthan, India

Date of Submission19-Apr-2020
Date of Acceptance05-Aug-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Manish Gupta
Department of Urology and Renal Transplant, Mahatma Gandhi Medical College, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_34_20

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  Abstract 


Introduction: The gold standard method for estimating glomerular filtration rate (GFR) in potential donors is diethylenetriaminepentaacetic acid (DTPA) renogram. But DTPA renogram being inconvenient, expensive, and with limited access , hence we need other methods which are noninvasive and provide a comparatively accurate estimation of GFR. Various estimating equations such as Cockcroft–Gault (CG) equation, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are available but have not been well studied or compared to DTPA GFR measurement. Methods: A total of 100 healthy donors (females and males) were studied. All participants underwent 99mTc DTPA renogram, and the GFR obtained was compared with MDRD, CG, and CKD-EPI-estimated GFR. Correlation between variables was estimated by statistical analyses in SPSS software version 18.0, and accuracy of various methods was studied. The data were analyzed by paired t-test, and Pearson's correlation test was used to correlate between two variables. Results: Out of the 100 donors, 79% were females and out of 100 renal recipients, 88% were males. The mean age for donors was 47.27 ± 10.93 years and for recipients was 35.02 ± 11.11 years. The mean GFR (mL/min per 1.73 m2) obtained by DTPA, CG, MDRD, and CKD-EPI was 109.91 ± 20.3, 114.10 ± 21.25, 128.66 ± 22.69, and 108.86 ± 12.72, respectively. The overall mean bias was smallest for CKD-EPI (standard deviation: 18.79). The bias and mean absolute difference between calculated and measured GFR for CKD-EPI, MDRD, and CG were 8.98 and 16.05, −17.97 and 23.26, and −5.76 and 23.29, respectively. There was a positive correlation between GFR by DTPA and GFR by CKD-EPI (0.408) and MDRD (0.399). Conclusions: Despite a wide variation in absolute values of GFR obtained by these methods, CKD-EPI and MDRD showed a positive correlation with DTPA GFR. CKD-EPI had least bias and thus correlated best with DTPA. In potential donors, these equations may be inadequate to replace DTPA for estimating GFR and due to limitations of our study further studies are needed with bigger sample size and longer duration.

Keywords: Chronic Kidney Disease Epidemiology Collaboration, Cockcroft–Gault method, DTPA, glomerular filtration rate, Modification of Diet in Renal Disease, renal donors


How to cite this article:
Malik S, Gill AP, Sadasukhi T C, Gupta HL, Gupta M, Patel K. Correlation of methods of glomerular filtration rate estimation: Cockcroft–gault equation, modification of diet in renal disease, chronic kidney disease epidemiology collaboration, and DTPA renography in prospective renal donors -a retrospective analytical study. Indian J Transplant 2020;14:230-4

How to cite this URL:
Malik S, Gill AP, Sadasukhi T C, Gupta HL, Gupta M, Patel K. Correlation of methods of glomerular filtration rate estimation: Cockcroft–gault equation, modification of diet in renal disease, chronic kidney disease epidemiology collaboration, and DTPA renography in prospective renal donors -a retrospective analytical study. Indian J Transplant [serial online] 2020 [cited 2020 Oct 20];14:230-4. Available from: https://www.ijtonline.in/text.asp?2020/14/3/230/296890




  Introduction Top


The increasing incidence of chronic kidney disease has led to an increased number of renal transplants. In developing countries like India, 90% of kidneys are donated by live donors.[1]

Assessment of renal function by measuring glomerular filtration rate (GFR) is the most important part of renal donor evaluation. The gold standard test for GFR estimation is inulin clearance, but it is not used routinely because of its technically very complex nature.[2],[3] The investigation of choice for estimating GFR is camera-based 99m Tc-diethylenetriaminepentaacetic acid (99m Tc-DTPA) renogram in clinical practice. However, the availability of this method outside large cities is still a constraint in low- and middle-income countries. Furthermore, due to the need for multiple samples and intravenous cannula, the method is inconvenient.

DTPA overestimates GFR by 3.5 mL/min in average compared to gold standard insulin GFR estimates. Thus, there is a need for alternative method, which is equally reliable and accurate.[4]

Various methods of estimating GFR are the Modification of Diet in Renal Disease (MDRD), Cockcroft–Gault (CG) method, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The degree to which these equations correlate to DTPA GFR measurement is not known. Thus, we conducted this study with a purpose to analyze the accuracy of these methods to estimate GFR with reference to GFR obtained by DTPA renogram.


  Methods Top


A retrospective analytical study was conducted from January 2018 to August 2019 in the Department of Urology, Mahatma Gandhi Medical College, Jaipur, Rajasthan. A total of 100 healthy renal transplant donors were included in the study.

The GFR was predicted from serum creatinine level, weight, and height using CG formula, MDRD, and CKD-EPI. This estimated GFR was compared with the GFR obtained by DTPA renogram. The measured GFR was normalized to 1.73 m2 of body surface area (BSA) for comparison.

Cockcroft-–Gault formula

(140 − age) × body weight/plasma creatinine × 72 (× 0.85 if female).

The value obtained was normalized per 1.73 m2 of BSA.

Modification of Diet in Renal Disease formula

175 × plasma creatinine −1.154 × age −0.203 (× 0.742 if female; × 1.21 if Black).

The value obtained was normalized per 1.73 m2 of BSA.

Chronic Kidney Disease Epidemiology Collaboration formula

  • Women with a plasma creatinine level ≤0.7: (plasma creatinine/0.7)−0.329 × (0.993) age (× 166 if Black: × 144 if White or other)
  • Women with a plasma creatinine >0.7: (Plasma creatinine/0.7)−1.209 × (0.993) age (× 166 if Black: × 144 if White or other)
  • Men with a plasma creatinine ≤0.9: (Plasma creatinine/0.9)−0.411 × (0.993) age (× 163 if Black: × 141 if White or other)


The value obtained was expressed as mL/min per 1.73 m2 of BSA.

Bias

DTPA–CG = CG bias

DTPA–MDRD = MDRD bias

DTPA–CKD-EPI = CKD-EPI bias.

Mean bias

Arithmetic mean of all CG bias = Mean CG bias

Arithmetic mean of all MDRD bias = Mean MDRD bias

Arithmetic mean of all CKD-EPI bias = Mean CKD-EPI bias.

Mean absolute bias

Values of individual BIAS are converted to absolute values (positive and negative signs are removed), and then the arithmetic mean of absolute values was calculated, showing mean absolute bias.

Statistical methods

Results from all the four methods (DTPA, CG, MDRD, and CKD-EPI) were analyzed statistically. The formulae were compared in terms of bias, precision, and accuracy. Bias was defined as the mean difference between the estimated and measured GFR. The standard deviation (SD) of the bias was termed as precision. Accuracy is the combination of both and was calculated as a percentage of patients who had estimated GFR within 30% of the GFR obtained by DTPA renogram. Pearson's correlation test was used to assess the relationship between the methods.

Declaration of patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity.

Ethics statement

It was a retrospective analysis and hence EC clearance was not needed. Study was carried out as per the declaration of helsinki.


  Results Top


A total of 100 healthy renal donors and 100 renal recipients were included in the study. Most of the renal donors were females (79%) and most of the renal recipients were males (88%).

Blood group distribution among the recipients was as follows: B+ve (37%), O+ve (29%), A+ve (28%), AB+ve (4%), and B−ve (2%).

The relation of the donor with the recipient was as follows: most of the renal donors were mother (39%) and wife (28%) [Table 1].
Table 1: Percentage-wise distribution of donors showing relationship with recipients

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The mean age for donors was 47.27 ± 10.93 years (25–69 years) and for recipients was 35.02 years ± 11.11 (16–66 years). The mean age for males was 52.47 years in donors and 35.13 years in recipients. The mean age for females was 45.88 in donors and 34.25 in recipients. The mean donor serum creatinine was 0.703 ± 0.068 mg/dL (0.5–0.9 mg/dL).

In DTPA, the right kidney was better functioning with a mean GFR of 55.16 (41.62–80.09), compared to left with a mean GFR of 50.5 (36.44–68.41) [Table 2].
Table 2: Differential function of right kidney compared to left kidney

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The mean GFR for DTPA was 109.91 and correlated best with CKD-EPI with a mean GFR of 108.86. In males, the mean DTPA GFR was 99.81, which also correlated best with CKD-EPI with a mean GFR of 114.40. The results were similar in females with DTPA mean GFR as 113.01 and again correlated best with CKD-EPI with a GFR of 107.21 [Table 3].
Table 3: Mean 99mTc-diethylenetriaminepentaacetic acid glomerular filtration rate comparison to mean Cockcroft-Gault, mean Modification of Diet in Renal Disease, and mean Chronic Kidney Disease Epidemiology Collaboration

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Compared to DTPA, CG and MDRD were negatively biased with mean bias values 5.76 and 17.97, respectively, whereas CKD-EPI was positively biased with a value of 8.98. Value of mean absolute bias (16.05) was also minimum with CKD-EPI.[Table 4] and [Figure 1].
Table 4: Bias, mean absolute bias, and standard deviation of Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration in comparison to 99mTc-diethylenetriaminepentaacetic acid

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Figure 1: Mean bias of Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease, and Cockcroft–Gault compared to 99mTc-diethylenetriaminepentaacetic acid

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On statistical analysis after calculating Pearson's correlation, CKD-EPI was found positively correlated with P < 0.05 with a Pearson's coefficient of 0.409. CG was found to be least and negatively correlated with a value of −037, however P value was >0.05 [Table 5].
Table 5: Pearson's correlation and P value of Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration

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A scatter plot comparing DTPA with CG, MDRD, and CKD-EPI was constructed. Data were found to be more scattered in CG compared to MDRD and CKD-EPI, showing best correlation [Figure 2], [Figure 3], [Figure 4].
Figure 2: Scatter plot comparing 99mTc-diethylenetriaminepentaacetic acid with Cockcroft–Gault. X-axis is age in years and Y-axis is glomerular filtration rate

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Figure 3: Scatter plot comparing 99mTc-diethylenetriaminepentaacetic acid with Modification of Diet in Renal Disease. X-axis is age in years and Y-axis is glomerular filtration rate

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Figure 4: Scatter plot comparing 99mTc-diethylenetriaminepentaacetic acid with Chronic Kidney Disease Epidemiology Collaboration. X-axis is age in years and Y-axis is glomerular filtration rate

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  Discussion Top


This study analyzed 100 healthy renal donors, and their GFR was calculated with CKD-EPI, MDRD, and CG formulas. These GFRs were compared with a standard relatively invasive and costly method such as DTPA. The study purpose was to find out if we can reduce the cost of transplant and can avoid some relatively invasive investigation such as DTPA.

Gender disparity was also analyzed along with differential renal function comparison with both kidneys. Most of the renal donors were females and most of the renal recipients were males. These data were supported by NOTTO, showing that majority of the donors were females and recipients were males. Around 23,682 males and a only 5025 females were recipients for organ transplant in India till 2019.[5]

Our study found that right kidney was better functioning compared to left kidney. A study by Gupta et al. on 398 healthy renal donors also showed that the right kidney was better functioning compared to the left, with the right kidney mean GFR of 52.93 and left kidney mean GFR of 49.12.[6]

CKD-EPI was found to be most accurate and precise with best Pearson's correlation and least SD. CG formula was found to be least precise and least correlated. Our study was consistent with other studies showing CKD-EPI as the best formula to calculate GFR. Mulay et al. concluded CKD-EPI as most precise and accurate and GATES protocol as least.[7]

Liu et al. studied 1196 Chinese participants (589 T2DM and 607 as nondiabetic) and compared MDRD and CKD-EPI with DTPA and found CKD-EPI correlated well with DTPA compared to MDRD, with 66.9% accuracy for CKD-EPI compared to MDRD with a accuracy of 55.2%.[8] In another study of 120 sickle cell patients with GFR >60/mL/min/1.73 m2, it was concluded that CKD-EPI is the best method to evaluate GFR.[9]

Jeong et al. measured GFR by EDTA method in 607 Korean patients and compared CKD-EPI and MDRD. They found least bias and best accuracy with CKD-EPI equation.[10] A study from Pakistan on 581 patients also supported that CKD-EPI is best compared to MDRD.[11] Our study confirms better accuracy of CKD-EPI equation in the Indian population compared to MDRD equation and CG formula.

Limitations of the study

Our study had few limitations. All the patients were healthy donors with GFR >60 mL/min/1.73 m2. Further studies are needed to apply this inference to patients with CKD. Special population groups such as diabetics, hypertensives, and those with other comorbidities were not included; thus, the applicability of our finding in these groups will also need further study.


  Conclusions Top


Most renal donors were females and most renal recipients were males. Social and psychological factors need to be addressed for this gender disparity.

Right kidney was found to be better functioning kidney compared to the left one.

Despite the wide variation in the absolute values of GFR obtained by these methods, CKD-EPI and MDRD showed a positive correlation with DTPA GFR. CKD-EPI had least bias and thus correlated best with DTPA. In potential donors, these equations may be inadequate to replace DTPA for estimating GFR and due to limitations of our study further studies are needed with bigger sample size and longer duration.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Shroff S. Current trends in kidney transplantation in India. Indian J Urol 2016;32:173-4.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Smith HW. The reliability of inulin as a measure of glomerular filtration. The Kidney Structure and Function in Health and Disease. New York: Oxford University Press; 1951. p. 231-8.  Back to cited text no. 2
    
3.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.  Back to cited text no. 3
    
4.
Qi Y, Hu P, Xie Y, Wei K, Jin M, Ma G, et al. Glomerular filtration rate measured by 99 mTc-DTPA renal dynamic imaging is significantly lower than that estimated by the CKD-EPI equation in horseshoe kidney patients. Nephrology 2016;21:499-505.  Back to cited text no. 4
    
5.
Available from: https://notto.gov.in/organreport.htm. [Last accessed on 2020 Jan 29].  Back to cited text no. 5
    
6.
Gupta M, Khadav B, Gupta HL, Sadasukhi TC. Comparison of differential function of both kidneys in a healthy renal donor. Indian J Transplant 2019;13:115-7.  Back to cited text no. 6
  [Full text]  
7.
Mulay AV, Gokhale SM. Comparison of serum creatinine-based estimating equations with gates protocol for predicting glomerular filtration rate in Indian population. Indian J Nephrol 2017;27:124-8.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Liu X, Gan X, Chen J, Lv L, Li M, Lou T. A new modified CKD-EPI equation for Chinese patients with type 2 diabetes. PLoS One 2014;9:e109743.  Back to cited text no. 8
    
9.
Uche CL, Osegbe ID. Comparison of CKD-EPI versus MDRD and Cockcroft-Gault equations to estimate glomerular filtration rate among stable homozygous sickle cell patients in Southwest Nigeria. Niger J Clin Pract 2017;20:816-21.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Jeong TD, Lee W, Chun S, Lee SK, Ryu JS, Min WK, et al. Comparison of the MDRD study and CKD-EPI equations for the estimation of the glomerular filtration rate in the Korean general population: The fifth Korea National Health and Nutrition Examination Survey (KNHANES V-1), 2010. Kidney Blood Press Res 2013;37:443-50.  Back to cited text no. 10
    
11.
Jessani S, Levey AS, Bux R, Inker LA, Islam M, Chaturvedi N, et al. Estimation of GFR in South Asians: A study from the general population in Pakistan. Am J Kidney Dis 2014;63:49-58.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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