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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 686-693
24-hour creatinine clearance reliability for estimation of glomerular filtration rate in different stages of chronic kidney disease

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 Publication26-Jun-2010


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 2023 Feb 4];21:686-93. Available from: https://www.sjkdt.org/text.asp?2010/21/4/686/64648

   Introduction Top

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 . [1] 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. [2]

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 . [1]

Creatinine clearance (CrCl.) is the most co­mmon method used to estimate GFR. This is done by either the Cockcroft-Gault (CG) for­mula, [3] 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. [4] 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. [5] Furthermore, it is impractical in large studies and dependent on muscle mass and thus creatinine generation decreasing with advancing age. [6] Furthermore inaccuracies in the measured serum Creatinine will affect the estimation of GFR as it is an important part of the equation. [7] GFR estimated by creatinine clearance is rather accurate only within the normal GFR. [8]

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. [9]

The most precise way to calculate GFR includes measurements of isotopic tracers and 99m Tc-DTPA showing excellent correlation with the gold standard techniques. [10],[11]

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 Top

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, [12],[13] 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. [4] In addition estimation of creatinine clearance was done according to the equation of CG. [3] 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 [14] and Mosteller formula. [15]

Dubois formula: [14]

BSA (m) 2 = 0.007184 Χ weight (kg) 0.425 Χ height (cm) 0.72514

Mosteller formula: [15]

   Statistical Analysis Top

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. [16]

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). [16],[17]

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 Top

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 Top

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 [18],[19],[20] 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. [21]

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, [22] 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 [23] was an in-accurate urine collection.

Star et al, [24] 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 [8] consequently creatinine based GFR estimates like CG equa­tions overestimate the true GFR. [25],[26]

Sobh et al, [27] 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, [28] 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.

   References Top

1.National Kidney Foundation. K/DOQI clinical practice guide lines for kidney disease: Part 5.Evaluation of laboratory measurements for clinical assessment of kidney disease. Am J Kidney Dis 2002;39:S76-92.  Back to cited text no. 1      
2.Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitali­zation. N Engl J Med 2004;351:1296-305.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Cockcroft AW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-4.  Back to cited text no. 3      
4.Clausen H. A simplified clearance method with formula clearance=UV/P. Med Monatsschr 1953; 7:656-7.  Back to cited text no. 4  [PUBMED]    
5.Levy AS, Berg RL, Gassman JJ, Hall PM, Walker WG. Creatinine filtration, Secretion, and excretion during progressive renal disease. Kidney Int 1989;36:S73-80.  Back to cited text no. 5      
6.Verhave JC, Balje-volkers CP, Hillege HL, DE Zeeuw D, Dejong PE. The Reliability of dif­ferent Formulae to predict creatinine clearance. J Intern Med 2003;253:567-73.  Back to cited text no. 6      
7.Refaie R, Moochhala SH, Kanagasundaram NS. How we estimate GFR-a pitfall of using a serum creatinine-based formula. Clin Nephrol 2007;68:235-7.  Back to cited text no. 7  [PUBMED]    
8.Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitation of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28:830-8.  Back to cited text no. 8  [PUBMED]    
9.Rehling M, Moller ML, Thamdrup B, Lund JO, Trap-Jensen J. Simultaneous measurement of renal clearance and plasma clearance of 99 Tc­labeled diethylenetriaminepenta-acetate. 51Cr labeled ethylenediaminetetra-acetate and inulin in man. Clin Sci 1984;66:613-9.  Back to cited text no. 9      
10.Buchler M, Bretagnol A, Desaldeleer C, et al. Estimation of the glomerular filtration rate through different methods in kidney transplant recipients: Correlatrion with the creatinine clea­rance measurement. Transplant Proc 2006;38: 2289-91.  Back to cited text no. 10      
11.Fotopoulos A, Bokharhli JA, Tsiouris S, et al. Comparison of six radionuclidic and non­radionuclidic methods for the assessment of glomerular filtration rate in patients with chronic renal failure. Hell J Nucl Med 2006; 9:133-40.  Back to cited text no. 11  [PUBMED]    
12.El Minshawy O, Guasch A. Performance of current equations for estimation of GFR in different stages of CKD among renal transplant recipients. Am J Kidney Dis 2008;51:B70.  Back to cited text no. 12      
13.El Minshawy O, Selvaraj S, Guasch A. Lack of accuracy of current formulae to estimate glo­merular filtration rate in U.S. renal transplant recipients. J Am Soc Nephrol 2007;18:683A  Back to cited text no. 13      
14.DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight are known. Ann Intern Med 1916;17: 863-71.  Back to cited text no. 14      
15.Mosteller RD. Simplified calculation of body­ surface area. N Engl J Med 1987;317:1098.  Back to cited text no. 15  [PUBMED]    
16.Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10.  Back to cited text no. 16  [PUBMED]    
17.Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res 1999;8:135-60.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]  
18.Lemann J, Bidani RP, Bain RP, Lewis EJ, Rohde RD. Use of the serum creatinine to estimate glo­merular filtration rate in health and early dia­betic nephropathy. Collaborative Study Group of Angiotensin Converting Enzyme Inhibition in Diabetic Nephropathy. Am J Kidney Dis 1990;16:236-43.  Back to cited text no. 18      
19.Coresh J, Astor BC, McQuillan G, et al. Cali­bration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 2002;39:920-9.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Mascioli SR, Bantle JP, Freier EF, Hoogwerf BJ. Artifactual elevation of serum creatinine level due to fasting. Arch Intern Med 1984; 144:1575-6.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]  
21.Rigalleau V, Lasseur C, Perlemoine C, et al. A simplified Cockcroft-Gault formula to improve the prediction of the glomerular filtration rate in diabetic patients. Diabetes Metab 2006;32: 56-62.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Perrone RD, Madias NE, Levey AS. Serum creatinie as an index of renal function: new insights into old concepts. Clin Chem 1992;38: 1933-53.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]  
23.Adam W: All that is excreted does not glisten: or why do we keep on collecting urine to measure creatinine clearance? Aust N Z J Med 1993;23:638.  Back to cited text no. 23      
24.Star R, Hostetter T, Hortin GL. New markers for kidney disease. Clin Chem 2002;48:1375­6.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]  
25.Kemperman FA, Krediet RT, Arisz L. Formula derived prediction of the glomerular filtration rate from plasma creatinine concentration. Nephron 2002;91:547-58.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]  
26.Walser M. Assessing renal function from creatinine measurements in adults with chronic renal failure. Am J Kidney Dis 1998;32:32.  Back to cited text no. 26      
27.Sobh M, Neamatallah A, Sheashaa H, et al. Sobh formula: a new formula for estimation of creatinine clearance in healthy subjects and patients with chronic renal disease. Int Urol Nephrol 2005;37:403-8.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]  
28.Poge U, Gerhartt T, Palmedo H, Klehr HU, Sauerbruch T, Woitas RP. MDRD Equations for estimation of GFR in renal Transplant Recipients. Am J Transplant 2005;5:1306-11.  Back to cited text no. 28      

Correspondence Address:
Osama El-Minshawy
Department of Internal Medicine/Nephrology, El-Minia University, School of Medicine, El-Minia
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Source of Support: None, Conflict of Interest: None

PMID: 20587873

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  [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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