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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 443-447
Comparison of 24-hour urinary protein and protein-to-creatinine ratio in the assessment of proteinuria


Division of Nephrology, Department of Internal Medicine, University of Jordan, Amman, Jordan

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   Abstract 

To determine the correlation between protein-to-creatinine ratio (PCR) and 24-hour urinary protein (UP), we measured proteinuria in 68 patients attending the nephrology clinic at Jordan University Hospital by 24-hour urine protein excretion and protein-to-creatinine ratio. The cutoff values for spot urine protein-to-creatinine ratio in predicting 24-hour protein "threshold" excretion of 0.5, 1.0 and 3.5 g/day were determined using receiver operating characteristic curves. A very good correlation (r= 0.832, P< 0.0001) was found between spot urine protein-to-creatinine ratio and 24-hour urine protein excretion. Bland-Altman plot showed the two tests had reasonable limits of agreement at low level of protein excretion but the limits became wider as the protein excretion increased. For protein excretion < 2.0 g/day, the limits of agreement of spot urine (PCR) and (UP) were +1.48 and -1.2 g/day. The spot urine protein-to-creatinine ratios of 0.72 (sensitivity 0.97; specificity 1.0), 1.2 (0.97; 0.89) and 3.23 (1.0; 0.86) mg/mg reliably predicted 24-hour urine total protein equivalent "thresholds" of 0.5, 1.0 and 3.5 g/day, respectively. We conclude that the protein-to-creatinine ratio in spot urine specimens is an accurate, convenient, and reliable method to estimate the protein excretion in urine. However, the protein-to-creatinine ratio will likely be within clinically acceptable limits only when proteinuria is at reasonably low levels.

Keywords: Proteinuria, 24-hour urine collection, Creatinine, Jordan

How to cite this article:
Wahbeh AM, Ewais MH, Elsharif ME. Comparison of 24-hour urinary protein and protein-to-creatinine ratio in the assessment of proteinuria. Saudi J Kidney Dis Transpl 2009;20:443-7

How to cite this URL:
Wahbeh AM, Ewais MH, Elsharif ME. Comparison of 24-hour urinary protein and protein-to-creatinine ratio in the assessment of proteinuria. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2017 Sep 22];20:443-7. Available from: http://www.sjkdt.org/text.asp?2009/20/3/443/50776

   Introduction Top


Measurement of protein excretion in a 24-hour urinary collection (UP) is the gold standard for the quantitative evaluation of proteinuria. How≠ever, this method is cumbersome and inconve≠nient, since it is difficult to collect a complete 24≠hour urine sample accurately, especially in the out≠patient setting. An alternative method for quan≠titative evaluation of proteinuria is the measure≠ment of protein-to-creatinine ratio (PCR) in an untimed spot urine specimen, which provides a more convenient method to assess protein ex≠cretion and is recommended by NKF K/DOQI guidelines. [1]

Although there is moderate to high correlation between PCR and UP, [2],[3],[4],[5],[6],[7] the agreement between these two measuring techniques should be as≠sessed when considering replacing one another. [8] Few studies have tested this agreement with va≠riable results. [9],[10],[11]

We aim in the present study to correlate the PCR and UP agreement, and attempt to find a discriminant value for PCR that reliably deter≠mines a significant threshold level of proteinuria.


   Subjects and Methods Top


Sixty-eight outpatients with proteinuria atten≠ding the nephrology outpatient clinic at Jordan University Hospital were evaluated. Although all patients were given clear instructions how to collect the urine accurately, 18 patients were ex≠cluded because the urine collection was ina≠dequate in 16 and over collected in two. The re≠maining 50 patients (29 men and 21 women) were included. Their average age was 51.1 Ī17.0 years. The mean protein excretion at the time of the study was 2.35 Ī2.47 gm and the mean PCR was 2.64 Ī2.75 mg/mg. The specimens of 24≠hour urine collections and random urine speci≠mens were collected within two days period.

The concentration of total protein in urine was measured by the turbidometric assay using benze≠thonium chloride, and the urine creatinine was measured by a creatinine Jaffe test using Ro≠che/Hitachi 917 analyzer.

Statistical Analysis

Data analysis was performed using MedCalc statistical software version 9.4.2.0 (demo ver≠sion). Spearman's correlation between the spot urine protein-to-creatinine ratio (PCR) and 24≠hour urine total protein (UP) was used. The limits of agreement between the two methods were analyzed by the Bland-Altman method, [8],[12] and inter-rater agreement Kappa. The discriminant cutoff values, sensitivity, and specificity of PCR were tested for predicting 24-hour protein excre≠tion "threshold" of 0.5, 1.0 and 3.5 g/day by re≠ceiver operating characteristic (ROC) curves. [13]


   Results Top


There was a very good correlation between spot urine (PCR) and 24-hour urine total protein (UP) (r= 0.832, P= 0.0001), [Figure 1]. Wide deviation from the line of identity was noticed at high pro≠tein excretion levels. As shown on Bland-Altman plot, the limits of agreement between PCR and UP were wide at high levels of protein excretion. These limits were better and similar across a wide range of protein excretion when data were log-transformed, [Figure 2]. For protein excretion < 2.0 g/day, the limits of agreement of spot urine (PCR) and (UP) were +1.48 and -1.2 g/day. With protein excretion < 1.0 g/day, the limits of agreement were +1.37 and -0.86 g/day. The inter-rater agreement Kappa was calculated and was 0.585, indicating moderate agreement between the two methods.

Using the ROC analysis, the urine PCR discri≠minant values of 0.72, 1.2 and 3.23 mg/mg re≠liably predicted 24-hour urine total protein of 0.5, 1.0 and 3.5 g/day, respectively, [Table 1].


   Discussion Top


A good correlation between the PCR and UP excretion has been demonstrated in patients with diabetic nephropathy, [11],[14],[15] renal transplant, [2],[3],[16] and pregnancy. [17] The NKF K/DOQI guidelines suggests that untimed spot urine samples should be used to detect and monitor proteinuria in chil≠dren and adults, it prefers a first-morning sample, but accepts a random sample if a first-morning specimen is not available.

The findings of our study showed a very good correlation between UP and PCR. To use both tests interchangeably, it is important to demons≠trate that both methods agree sufficiently. Few studies have previously assessed agreements ra≠ther than correlations between these tests and found wide limits. [9],[10],[11] In our study, the limits of agreement were also wide, but similar across a wide range of protein excretion when data were log-transformed, the absolute difference between PCR and UP becomes very large as protein ex≠cretion increases. The inter-rater agreement Ka≠ppa was calculated and was 0.585 (KW= 0 of 0.087 and KW # 0 of 0.053) indicating moderate agreement between both methods.

Urinary protein excretion is not constant and daily excretion varies by as much as 40% besides repeated 24-hour urine protein excretion varies by at least 15%. [9] Rodby et al. repeated measure≠ments on 33 patients at least three months apart and found discordant results were the PCR in≠creased in some patients whereas the UP fell, and vice versa. [18] Agrawal found a day to day varia≠bility in 24-hour urinary protein excretion of 10% and in protein-to-creatinine ratio of 2%. [19] This variability is a likely reason for the poor agree≠ment between the two methods of assessing proteinuria.

By using the ROC curves, the PCR of 0.72, 1.2 and 3.28 mg/mg in spot urine specimens represents the best threshold to reliably detect urine protein excretion of 0.5, 1 and 3.5 g in 24-hour collec≠tions respectively, with high sensitivity, specifi≠city, and area under ROC curve. The sensitivity and specificity in the present study are consistent with the previously published reports. [20],[21],[22],[23],[24]

We conclude that the PCR in spot urine spe≠cimens is an accurate, convenient, and reliable method to estimate the protein excretion in urine. However, when the exact amount of protein ex≠cretion is required, then a PCR will likely be within clinically acceptable limits only when pro≠teinuria is at reasonably low levels.

 
   References Top

1.Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): A position paper of the National Kidney Foundation. Am J Kidney Dis 1999; 33:1004-10.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Dyson EH, Will EJ, Davidson AM, et al. Use of the urinary protein creatinine index to assess proteinuria in renal transplant patients. Nephrol Dial Transplant 1992;7:450-2.  Back to cited text no. 2    
3.Steinhauslin F, Wauters J. Quantitation of pro≠teinuria in kidney transplant patients: Accuracy of urinary protein/creatinine ratio. Clin Nephrol 1995;43:10-15.  Back to cited text no. 3    
4.Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to esti≠mate quantitative proteinuria. N Engl J Med 1983;309:1543-6.  Back to cited text no. 4  [PUBMED]  
5.Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional longitudinal study of spot morning urine protein: Creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate and end stage renal failure in chronic renal disease in patients without diabetes. Br Med J 1998;316:504-8.  Back to cited text no. 5    
6.Ralston SH, Caine N, Richards I et al. Screening for proteinuria in a rheumatology clinic: Com≠parison of dipstick testing, 24 hour urine quan≠titative protein and protein/creatinine ratio in random urine samples. Ann Rheum Dis 1998; 47:759-63.  Back to cited text no. 6    
7.Schwab S, Christensen L, Dougherty K, Klahr S. Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med 1987;147:943-4.  Back to cited text no. 7    
8.Bland M, Altman D. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-11.  Back to cited text no. 8    
9.Chitalia VC, Kothari J, Wells EJ, et al. Cost≠benefit analysis and prediction of 24 hour pro≠teinuria from the spot urine protein-creatinine ratio. Clin Nephrol 2001;55:436-47.  Back to cited text no. 9  [PUBMED]  
10.Mitchell SCM, Sheldon TA, Shaw AB. Quanti≠fication of proteinuria: A re-evaluation of the protein/creatinine ratio for elderly subjects. Age Ageing 1993;22:443-7.  Back to cited text no. 10    
11.Cundy TF, Nixon D, Berkahn L, Baker J. Mea≠suring the albumin excretion rate: Agreement methods and biological variability. Diabetes Med 1992;9:138-43.  Back to cited text no. 11    
12.Bland J, Altman D. Measuring agreement in method comparison studies. Stat Met Med Res 1999;8:135-60.  Back to cited text no. 12    
13.Fawcett T. An introduction to ROC analysis. Pattern Recog Lett 2006;27:861-74.  Back to cited text no. 13    
14.Zelmanovitz T, Paggi A, Gross JL, Tatsch M, Oliveria JR, Azevedo MJ. The receiver ope≠rating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care 1997;20:5 16-9.  Back to cited text no. 14    
15.Zelmanovitz T, Oliveira J, Gross JL, Azevedo MJ. Proteinuria is still useful for the screening and diagnosis of overt diabetic nephropathy. Diabetes Care 1998;21:1076-9.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Torng S, Rigatto C, Rush DN, Nickerson P, Jeffery JR. The urine protein to creatinine ratio (P/C) as a predictor of 24-h urine protein excre≠tion in renal transplant patients. Transplantation 2001;72:1453-6.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Neithardt AB, Dooley SL, Borensztajn J. Pre≠diction of 24-h protein excretion in pregnancy with a single voided urine protein-to-creatinine ratio. Am J Obstet Gynecol 2002;186:883-6.  Back to cited text no. 17    
18.Rodby RA, Rohde RD, Sharon Z, Pohl MA, Bain RP, Lewis EJ. The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. Am J Kidney Dis 1995;26:904-9.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Agrawal R. Reproducibility of renal function measurements in adult men with diabetic nephropathy: Research and clinical implica≠tions. Am J Nephrol 2007;27:92-100.  Back to cited text no. 19    
20.Quadri K, Bernardini J, Greenberg A, Laifer S, Syed A, Holley JL. Assessment of renal function during pregnancy using random urine protein to creatinine ratio and Cockcroft-Gault formula. Am J Kidney Dis 1994;24:416-20.  Back to cited text no. 20    
21.Young RA, Buchanan RJ, Kinch RA. Use of the protein/creatinine ratio of a single voided urine specimen in the evaluation of suspected preg≠nancy-induced hypertension. J Fam Pract 1996; 42:385-9.  Back to cited text no. 21  [PUBMED]  
22.Robert M, Sepandj F, Liston RM, Dooley KC. Random protein creatinine ratio for the quantita≠tion of proteinuria in pregnancy. Obstet Gynecol 1997;90:893-5.  Back to cited text no. 22  [PUBMED]  
23.Ramos JG, Martins-Costa SH, Mathias MM, Guerin YL, Barros EG. Urinary protein/crea≠tinine ratio in hypertensive pregnant women. Hypertens Pregnancy 1999;18:209-18.  Back to cited text no. 23  [PUBMED]  
24.Rodriguez-Thompson D, Lieberman ES. Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Am J Obstet Gynecol 2001;185: 808-11.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Ayman M Wahbeh
Assistant Professor of Medicine, University of Jordan, P.O. Box 1374, Amman 11941
Jordan
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PMID: 19414948

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