|Year : 2010 | Volume
| Issue : 4 | Page : 686-693
|24-hour creatinine clearance reliability for estimation of glomerular filtration rate in different stages of chronic kidney disease
Osama El-Minshawy1, Rafet A Saber2, Ashraf Osman3
1 Department of Internal Medicine, El Minia University School of Medicine, El Minia, Egypt
2 Department of Clinical Oncology and Nuclear Medicine, El Minia University School of Medicine, El Minia, Egypt
3 Department of Clinical Pathology, El Minia University School of Medicine, El Minia, Egypt
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|Date of Web Publication||26-Jun-2010|
| Abstract|| |
Glomerular Filtration Rate (GFR) is considered the best overall index of renal function currently used. Measurement of 24 hours urine/plasma creatinine ratio (UV/P) is usually used for estimation of GFR. However little is known about its accuracy in different stages of Chronic Kidney Disease (CKD) aim: is to evaluate performance of UV/P in classification of CKD by comparing it with isotopic GFR (iGFR). 136 patients with CKD were enrolled in this study 80 (59%) were males, 48 (35%) were diabetics. Mean age 46 ± 13. Creatinine Clearance (Cr.Cl) estimated by UV/P and Cockroft-Gault (CG) was done for all patients, iGFR was the reference value. Accuracy of UV/P was 10%, 31%, 49% within ± 10%, ± 30%, ± 50% error respectively, r 2 = 0.44. CG gave a better performance even when we restrict our analysis to diabetics only, the accuracy of CG was 19%, 47%, 72% in ± 10%, ± 30% and ± 50% errors respectively, r 2 = 0.63. Both equations gave poor classification of CKD. In conclusion, UV/P has poor accuracy in estimation of GFR, The accuracy worsened as kidney disease becomes more severe. We conclude 24 hours CrCl. is not good substitute for measurement of GFR in patients with CKD.
|How to cite this article:|
El-Minshawy O, Saber RA, Osman A. 24-hour creatinine clearance reliability for estimation of glomerular filtration rate in different stages of chronic kidney disease. Saudi J Kidney Dis Transpl 2010;21:686-93
|How to cite this URL:|
El-Minshawy O, Saber RA, Osman A. 24-hour creatinine clearance reliability for estimation of glomerular filtration rate in different stages of chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Jul 8];21:686-93. Available from: http://www.sjkdt.org/text.asp?2010/21/4/686/64648
| Introduction|| |
Chronic Kidney Disease (CKD) is defined as structural or functional abnormalities that persist for at least three months and are manifested by either kidney damage most frequently detected as persistent albuminuria > 30 mg albumin/g creatinine or a decreased Glomerular Filtration Rate (GFR) < 60 mL/min/1.73m 2 .  CKD alone is an independent risk factor for the development of coronary heart disease; recent studies have confirmed that even early CKD constitute a significant risk factor for cardiovascular events and death. 
Assessment of GFR is the best overall index of kidney functions; Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation has elaborated a classification of CKD based on estimated glomerular filtration rate (GFR). The guidelines also recommend that patients be assigned to one of five stages based on the level of GFR stage 1 ≥ 90 mL/ min/1.73m 2 , stage 2 (60-89) mL/min/1.73m 2 , stage 3 (30-59) mL/min/1.73m 2 , stage 4 (15-29) mL/min/1.73m 2 , stage 5 < 15 mL/min/1.73m 2 . 
Creatinine clearance (CrCl.) is the most common method used to estimate GFR. This is done by either the Cockcroft-Gault (CG) formula,  or by using a 24-hour urine collection as a routine stander for the measurement of the urine to plasma ratio of creatinine (UV/P) expressed as mL/minute.  Nevertheless this formula is dependent on collection of an accurate 24 hour urine which is inconvenient for the patient and is prone to collection failures and thus errors.  Furthermore, it is impractical in large studies and dependent on muscle mass and thus creatinine generation decreasing with advancing age.  Furthermore inaccuracies in the measured serum Creatinine will affect the estimation of GFR as it is an important part of the equation.  GFR estimated by creatinine clearance is rather accurate only within the normal GFR. 
A number of compounds labeled with radioisotopes have been employed for assessment of GFR. Because of a greater ease of administration, simplicity, accuracy, and precision of measurement, their use is desirable. One of the readily available and routinely used methods is diethylene triamine pentaacetic acid ( 99m Tc-DTPA) isotopic clearance. This method was compared with the 51 -Cr EDTA and inulin clearance, based on the single injection technique, and the correlation was 0.97 was observed. 
The most precise way to calculate GFR includes measurements of isotopic tracers and 99m Tc-DTPA showing excellent correlation with the gold standard techniques. ,
The aim of the study was to evaluate the performance of UV/P, its accuracy and precision in predicting GFR and its validity in classification of CKD in Egyptian patients.
| Methods|| |
Patients included in the study were from the outpatient clinic, El-Minia University Hospital, El-Mina, Egypt all patients have CKD according to K/DOQI guide lines of the National Kidney Foundation. In all one hundred and thirty six patients were included. We have previously reported lack of accuracy of current formulae to estimate GFR, , so in the current study we focus on validity of 24 hours creatinine clearance as a method for estimation of GFR.
We collected 24 hours urine for 136 patients, as an out patient, adequacy of urine collection dependent on the patients themselves as most of them were educated, cooperative and they were informed of the way of collection and conservation of the 24-hour urine sample prior to analytical processing at our centre. All patients included in the study provided their consent.
Age, body weight, height, SCr were reported at the same day of the study, where urine and plasma samples were taken. 24 hour urine creatinine clearance was estimated using UV/P formula. Where U is the concentration of creatinine in urine in mg/dL and V is the volume of urine produced per minute and P is the plasma creatinine in mg/dL.  In addition estimation of creatinine clearance was done according to the equation of CG.  eGFR (mL/min) ) = (140 - age) Χ body weight/(72 Χ SCr) (Χ 0.85 for women) (In this formula SCr is in mg/dL, age in years).
The patients were hydrated orally at 10 mL water/kg body weight before the start of the study. Diethylene triamine pentaacetic acid ( 99m Tc-DTPA) dosed at 50 ΅Ci/kg was injected intravenously.
Initial rapid sequences of dynamic images were acquired to assess renal perfusion every four seconds for 30 minutes Nd time activity curve was generated using computer software. Sequential static images were also acquired three hours after intravenous injection of 99m TcDTPA to evaluate renal cortical uptake.
The results of the UV/P, CG and iGFR were corrected to body surface area (BSA) of 1.73 m 2 (1.73/BSA) BSA was estimated according to Dubois' formula  and Mosteller formula. 
Dubois formula: 
BSA (m) 2 = 0.007184 Χ weight (kg) 0.425 Χ height (cm) 0.72514
Mosteller formula: 
| Statistical Analysis|| |
Results are shown as mean ± SD, correlation between variables was performed using commercially available statistical software (minatab 15). The percent error in GFR prediction was calculated as: % prediction error = (predicted value-measured value)/(measured value) Χ 100.
Accuracy for each eGFR formula was assessed as the proportion of GFR estimates within 10%, 30%, and 50% deviation of the true GFR. 
Precision was determined as root mean square error (RMSE), where RMSE = Standard deviation of the mean difference between real GFR and estimated GFR.
Bland-Altman recommendations were used to compare the GFR calculated with prediction equations compared with renal clearance of 99m TC-DTPA (the reference method). ,
Measures of accuracy (i.e. nearness of the reduced major axis of the data to the line of perfect concordance) and precision (i.e. tightness of the data around their reduced major axis) determine whether data observed significantly diverge from the line of perfect concordance, which occurs at 45 degrees. The BlandAltman limits of agreement procedure uses data scale assessment in analyzing both the accuracy (i.e. bias) and amount of variation or precision between any two measured values when the range of data is sufficiently limited.
Percent error in eGFR prediction by 24 hours creatinine clearance = (predicted value-measured value) / (measured value) Χ 100.
Accuracy was calculated as the Proportion of GFR estimates within ± 10, ± 30, and ± 50% deviation from the true GFR.
Precision was estimated from the root mean square error (RMSE=standard deviation of the mean difference between true GFR and estimated GFR).
| Results|| |
One hundred and thirty six patients with CKD were included in this study. 80(59%) were males , 48 (35%) patients were diabetics and the mean age was 46 ± 13 years (21-72 years).Their BMI was 30 ± 7, BSA was 1.95 ± 0.2 and mean serum creatinine and blood urea nitrogen were 2 ± 0.9 mg/dL and 34 ± 15 mg/ dL respectively. Creatinine clearance estimated by UV/P and CG was done for all patients. Measurement of GFR by renal scintigraphy was used as a reference method. The mean measured GFR by renal scintigraphy was 37 ± 19 mL/min/1.73m 2 . While the mean eGFR by CG was 50 ± 22 mL/min/1.73m 2 and by UV/P CrCl was 58 ± 45 mL/min/1.73m 2 .
In order to evaluate the correlation of creatinine clearance to GFR, comparison with the renal scintigraphy was carried out. To determine if creatinine clearance provides accurate information on the GFR we calculated the prediction error. In UV/P not more than 10% of estimated values were within ± 10% error 31% of estimated values were within ± 30 %, 49% of estimated values were within ± 50%. r 2 = 0.44. CG gave a better performance than UV/P with accuracy of 13%. 47% and 72% in ± 10%, ± 30% and ± 50% errors respectively, r 2 = 0.63 [Table 1]. Detailed description of clini-cal characteristics are given in [Table 2]. When we restricted our analysis to diabetics and non diabetics only CG was also gave better accuracy than UV/P [Table 3], [Table 4], [Table 5], [Table 6].
The classification of CKD according to measurement of GFR 99m TC-DTPA distributed as follows: Stage 1 (n=2), Stage 2 (n=14), Stage 3 (n=68), Stage 4 (n=40), Stage 5 (n=12) [Table 7]. On testing the validity of UV/P and Cockroft-Gault to classify CKD correctly we found that in stage 2 both equations classified only 43% of their estimation of GFR correctly. In stage 3, UV/P classified only 38% correctly, while CG classifies 68% correctly. In Stage 4, UV/P classified only 25% correctly; this percent was 30% for CG. In stage 5 the validity of both equations to classify CKD was Zero % [Table 8]. This result clearly shows from these results we can found that worsening of accuracy of UV/P as the kidney disease become more severe. On evaluation of the validity of both equations to classify CKD we found both equations were poor to classify CKD.
| Discussion|| |
Our results clearly show the lack of accuracy of 24 hour urine CrCl and eGFR calculation by CG formula in comparison to 99m Tc DTPA scan with advancing CKD. In patients with CKD estimation of the GFR is necessary evaluation of complications and of CKD and proper dosing of drugs. Our results illustrated that overestimation of the GFR was observed.
The results obtained in the current study demonstrated that equation dependent on the collection of 24-hour urine samples is unreliable this is in agreement of previous studies ,, this inaccuracy may be attributed to the possibility of imprecision in the collection and conservation of the sample, as well as variability in the inter-hospital calibration methods employed.
Our results showed that CG had a stronger correlation overall r 2 = 0.63 [Figure 1], diabetic patients r 2 = 0.54 [Figure 2] and non diabetic patients r 2 = 0.63 [Figure 3] in agreement with the study by Rigalleau et al. 
Moreover, the simultaneous application of the two methods provided a correct and concordant stratification of CKD in only 50% of the patients which seems still is quite low. Perrone et al,  also reported that the lack of accuracy by 24 hours creatinine clearance varying dramatically with the true GFR measured by renal scintigraphy. The most important factor in our patients and as reported by Adam  was an in-accurate urine collection.
Star et al,  reported that serum creatinine concentration is influenced by muscle mass, dietary protein intake, sex and age thus limiting the precision of creatinine based methods. Furthermore in patients with reduced GFR tubular secretion of creatinine increases  consequently creatinine based GFR estimates like CG equations overestimate the true GFR. ,
Sobh et al,  evaluated different methods for GFR estimation and that measured by 99m TcDTPA, in their group of CKD patients, they found that r for CG formula was 0.61 while it was 0.27 in UV/P similar to our study.
Poge et al,  also reported similar over estimations in renal transplant patients.
In conclusion, 24 hour CrCl is not a reliable estimate of the GFR in Egyptian patients with CKD to classify the stages of CKD. It is, therefore, not an accurate substitute for measurement of GFR by radionuclide method by 99mTc-DTPA scan.
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Department of Internal Medicine/Nephrology, El-Minia University, School of Medicine, El-Minia
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]
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