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NDT Advance Access published online on November 26, 2008

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn639
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Diagnostic accuracy of a reagent strip for assessing urinary albumin excretion in the general population

Maria Stella Graziani1, Giovanni Gambaro2, Lucilla Mantovani1, Alessandro Sorio1, Tewoldemedhn Yabarek2, Cataldo Abaterusso2, Antonio Lupo2 and Paolo Rizzotti1

1 Laboratorio di Analisi Chimico Cliniche ed Ematologiche, Ospedale Civile Maggiore 2 Dipartimento di Scienze Biomediche e Chirurgiche, Divisione di Nefrologia, Università degli Studi di Verona and Ospedale Civile Maggiore, Azienda Ospedaliera di Verona, Italy

Correspondence and offprint requests to: Maria Stella Graziani, Laboratorio di Analisi Chimico Cliniche ed Ematologiche, Ospedale Civile Maggiore, Azienda Ospedaliera di Verona, piazzale Stefani, 1 37126 Verona, Italy. Tel +39-045-812-2421; Fax: +39-045-812-356; E-mail: mariastella.graziani{at}azosp.vr.it



   Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. Albuminuria is a sensitive marker of renal derangement and has been included in a number of studies investigating chronic kidney diseases (CKDs). This study is aimed to evaluate the diagnostic performances of a strip for measuring the albumin/creatinine ratio (ACR) in the general population and to compare it with those found in a diabetic population.

Methods. Urine samples were obtained from 201 consecutive subjects enrolled in an epidemiological study and from 259 type 2 diabetic patients. Urine was tested for albumin and creatinine using the strip (Clinitek Microalbumin) and laboratory methods. A hundred samples were stored under various conditions to assess analyte stability.

Results. In the general population, the strip test reached a 90% sensitivity and 91% specificity, considering the laboratory method as the ‘gold standard’, sparing >80% of subjects the laboratory tests at the expense of a 1% false negative rate and an 8% false positive rate. Regarding sensitivity and specificity, the ACR test performs very similarly in the general population and in the diabetics. The stability study showed that storage at –20°C induced a significant decrease in the albumin concentration with both methods, such that 5% of the samples were re-classified in the lower ACR class. Storage at –80°C for up to 12 months did not affect the measurement with both methods.

Conclusion. Clinitek Microalbumin strips can be used for screening purposes in the general population since they correctly classify a significant percentage of subjects, particularly those with a normal albuminuria. Storage at –80°C does not affect strip results. Screening with the strip and confirming positive results with a wet chemistry method are an efficient strategy for detecting albuminuria in the general population.

Keywords: albumin/creatinine ratio; CKD; diabetic nephropathy; dipstick urinalysis; screening



   Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
While the burden of chronic kidney disease (CKD) and end-stage renal disease is increasing dramatically in both developed and developing countries, most subjects in the earlier stages of kidney disease go undiagnosed and under-treated [1–3]. Finding solutions for renal disorders demands strategies not only to prevent the adverse outcome of kidney disease but also to detect kidney impairment as early as possible.

Albuminuria is considered a sensitive marker of renal derangement and is included in the definition of CKD stages 1 and 2 by the US National Kidney Foundation [4]. High albumin concentrations in the urine are typical of several common diseases and conditions, such as hypertension, diabetes and obesity, and are considered a marker of endothelial dysfunction and cardiovascular risk [5–7], which is why laboratory testing of urinary albumin has been included in a number of ad hoc epidemiological studies [8,9].

In 2006, we launched the ‘INCIPE’ study (Initiative on Nephropathy of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points) in Northeastern Italy to assess the prevalence of CKD in the Italian population. This is a multicentre study on a random sample of the general population over 40 years of age [10]. The albumin/creatinine ratio (ACR) is a recommended method for estimating albumin excretion [4,5], and was one of the tests performed in the subjects recruited for the study. Since the prevalence of microalbuminuria in the general population is low [3,9], prescreening with a dry chemistry test could be an effective way to spare a considerable number of subjects the laboratory tests. Clinitek Microalbumin is an ACR test strip that has performed well in a number of studies, especially in diabetic patients [11–13], but its diagnostic performance in the general population and how it is influenced by sample storage temperatures have not been investigated.

The aim of the present study was to evaluate the analytical characteristics of this strip in measuring albumin and creatinine in urine, comparing them with the corresponding laboratory test, to establish whether it could be used for screening purposes in the general population. The strip's performance in the general population was compared to the one observed in diabetic patients, in whom the strip is most commonly used.



   Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Sample selection and comparison study
Freshly voided early-morning urine was collected consecutively from 201 participants in the INCIPE study and from 259 type 2 diabetic patients attending the hospital's diabetic clinic. Urine was tested within 5 h of collection using both the strip and laboratory methods.

Strip test
We used plastic strips (Clinitek Microalbumin, Siemens Medical Solutions Diagnostics, Mishawaka, IN, USA) with two reaction areas for albumin and creatinine. The area for albumin is impregnated with a high-affinity-specific dye (tetrabromosulfo-nephthalein) [14], while the creatinine test is based on the peroxidase-like activity of a copper–creatinine complex [15]. The colour yields of the two reactions are assessed using a small bench-top reflectance meter (Clinitek Status, Siemens Medical Solutions Diagnostics, Mishawaka, IN, USA). The device provides a semi-quantitative estimate of the albumin content in four categories (10, 30, 80, 150 mg/L) and of the creatinine in five categories (0.9, 4.4, 8.8, 17.7, 26.5 mmol/L). The ACR is also given in three categories (<3.4, 3.4–33.9, >33.9 mg/ mmol), calculated using the effective albumin and creatinine concentrations, not the related categories.

Laboratory methods
Albumin was measured immunochemically using a specific antibody and a nephelometer (Immage 800, Beckman Coulter, Inc., Fullerton, CA, USA); creatinine was measured on the RxL Dimension (Siemens Medical Solutions Diagnostics, Newark, DE, USA) using an alkaline picrate method. Urine protein electrophoresis on agarose gel was performed in the false positive samples. We also performed the strip test on three samples with pure Bence Jones proteinuria (lambda or kappa chains >1000 mg/L) to ascertain whether this could influence the albumin measurement.

Precision
Specimens in the three ACR categories were used to test repeatability, using the strip to take the measurements 10 times on two separate occasions (i.e. 20 measurements in all for each category).

Stability test
The first 100 consecutive specimens from the INCIPE study were divided into aliquots to test albumin and creatinine stability under various conditions (+4°C, –20°C, –80°C). Time points were set at 24 h (+4°C), and 12 months (–20°C and –80°C). The aliquots were thawed at room temperature, thoroughly mixed by inversion, centrifuged and then analysed with both the strip and the laboratory methods.

Statistics
The statistical analysis on the performance of the diagnostic test was conducted using the free software available on http://www.quantitativeskills.com/sisa/statistics/diaghlp. htm. Student's t-test for paired data was used wherever necessary.



   Results
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 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
The ACR range with albumin measured by nephelometry was 0.09–300 mg/mmol in the general population and 0.22–775 mg/mmol in diabetics.

Table 1 shows the results of the comparison between the strip and the laboratory methods for testing ACR, using a cut-off of 3.4 mg/mmol to define microalbuminuria, as suggested in the American Diabetes Association guidelines [5,16]. When the ACR was tested in the general population, the sensitivity and specificity of the strip method were 90 ± 7 SE% and 91 ± 2 SE%, respectively; the positive predictive value (PPV) was 53 ± 9 SE%, and the negative predictive value (NPV) was 99 ± 2 SE%. The concordance index between the strip and the laboratory reference assay was 91 ± 2 SE%.


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Table 1 Sample classification for ACR (cut-off <3.4 mg/mmol) measured by the strip and laboratory methods in the general population (n = 201 subjects) and type 2 diabetic patients (n = 259)

 
In the diabetic group, the sensitivity and specificity of the ACR strip method were 91 ± 4 SE% and 92 ± 2 SE%, respectively; the PPV was 71 ± 6 SE%, and the NPV was 98 ± 2 SE%. The concordance index was 92 ± 2 SE%.

The overall concordance index between the strip and the laboratory assay (in 460 samples) was 91 ± 1 SE%.

The false-positive samples (n = 34) did not have a particularly high urinary pH (all <8) or a particular protein pattern on agarose gel electrophoresis (glomerular or tubular proteinuria). The albumin measurements performed with the strip and the nephelometric method in the three samples with Bence Jones proteinuria were in complete agreement.

The repeatability studies returned a consistency of 100% for the ACR categories <3.4 and >33.9 mg/mmol, and 95% in the 3.4–33.9 mg/mmol category (one sample was placed once in the <3.4 class).

Table 2 shows the results of the comparison studies between the strip test and the laboratory method for albumin measurement considering as negative the samples with albumin concentration <20 mg/L by the nephelometric method or classified in the lowest category by the strip test. The cut-off was chosen taking into account that the ‘label’ of the lowest albumin class in the strip test (10 mg/L) represents the central value of the concentration range 0– 20 mg/L (similarly, the following class labelled as 30 ranges from 20 to 55 mg/L, etc.) [12,17]. In the general population, the sensitivity and specificity of the strip method were 90 ± 5 SE% and 85 ± 3 SE%, respectively; the PPV was 51 ± 7 SE%, and the NPV was 98 ± 2 SE%. The concordance index between the strip and the laboratory reference assay was 86 ± 2 SE%.


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Table 2 Sample classification for urinary albumin measured by the strip and laboratory methods in the general population (n = 201 subjects) and type 2 diabetic patients (n = 259)

 
In the diabetic group, the sensitivity and specificity of the strip test were 92 ± 4 SE% and 95 ± 2 SE%, respectively; the PPV was 83 ± 5 SE%, and the NPV was 97 ± 2 SE%. The concordance index was 94 ± 1 SE%. However, the comparison between Table 1 and Table 2 that shows quite clearly the higher detection capability of negative results by the ACR strip versus the albumin strip test in the general population (167 versus 148, respectively) is noteworthy.

ACR and albumin values as determined by the laboratory methods in samples giving discrepant results (false-positive or false-negative) at the strip test are shown in Figures 1 and 2, respectively; the diabetics and the general population are presented separately. Both the number of discordant tests and the wideness of the distribution are quite similar in the two studied populations. Figure 3 shows the results of the stability study when measurements were performed with the strip test. No change in the ACR class was observed when samples were stored at +4°C for 24 h or at –80°C for 12 months, whereas storage at –20°C for 12 months made 5% of the samples shift from the 3.4–33.9 mg/mmol class to the <3.4 mg/mmol class. A similar shift towards lower concentration classes was observed for albumin, while the creatinine measurements remained stable. The mean albumin concentration measured with the nephelometric method decreased significantly (57.4 ± 28.6 SE versus 46.7 ± 24.28 SE mg/L, P < 0.01) in the samples stored at –20°C for 12 months compared with the fresh samples, whereas those stored at +4°C for 24 h (57.3 ± 28.9 SE) and at –80°C for 12 months (58.6 ± 30.9 SE) showed no statistically significant differences. The range of the albumin concentration in the fresh samples used for the stability study was very large (from <2 to 2520 mg/L), but in the six samples with albumin concentration >30 mg/L, the percentage differences were similar to those observed in the samples with lower concentrations. No significant variation was observed in the creatinine concentrations in samples stored under different conditions (data not shown).


Figure 1
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Fig. 1 ACR values as determined by the laboratory methods in samples giving discrepant results (false-positive or false-negative) at the strip test. Samples are classified as false negative and false positive according to the cut-off of 3.4 mg/mmol creatinine, and grouped by type of investigated subjects (diabetics or general population).

 

Figure 2
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Fig. 2 Albumin concentration values as determined by nephelometry in samples giving discrepant results (false-positive or false-negative) at the strip test. Samples are classified as false negative and false positive according to the cut-off of 20 mg/L, and grouped by type of investigated subjects (diabetics or general population).

 

Figure 3
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Fig. 3 Sample distribution in the different ACR classes under various storage conditions: ACR <3.4 mg/mmol in white area; ACR 3.4– 39.9 mg/mmol in grey area; ACR >3.4 mg/mmol in black area. The storage conditions were +4°C for 24 h; –20°C and –80°C for 12 months. Percentages are shown.

 


   Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
It is well recognized that CKD is a relevant problem all over the world; the early stages of kidney dysfunction are clinically silent and are detected only by laboratory investigations [1–3]. Albumin excretion is considered a sensitive marker of renal derangement, and its measurement is included in the assessment of renal function [4]. In the most important studies where the test was performed in the general population, i.e. the NHANES [3], HUNT [8] and Prevend [9] studies, wet chemistry methods (nephelometry) were used. In the framework of the INCIPE study examining more than 6000 people over 40, a random sample of the general population living in Northeastern Italy, we have evaluated the stability, precision and diagnostic performances of a strip for detecting the abnormal ACR. To the best of our knowledge, this is the first analysis of the performance of a strip test to detect albuminuria in the general population since dry chemistry methods have been generally used in the clinical setting only, as point-of-care tests.

While the laboratory test remains the ‘gold standard’ for microalbuminuria, using a cut-off of 3.4 mg/mmol for ACR [5,16], the strip test classified 165 of 201 samples (82%) from the general population as negative, with only two false-negative cases, and 194 of 259 samples from the diabetic group (75%), with only four false-negative cases (Table 1).

The performance of the Clinitek Microalbumin test in the diabetic group was similar or even better than previously reported. In 302 consecutive diabetic patients, Le Floch et al. [13] found a sensitivity of 79%, a specificity of 81%, a PPV of 46% and an NPV of 95%, with a concordance index of 92% and a K-value of 0.47. In 252 consecutive diabetic patients, Croal et al. recorded a concordance index of 89% [18]. In 156 spot urine samples from diabetic children, Meinhardt et al. [19] obtained a sensitivity of 89% and a specificity of 73%, with a PPV of 17% and an NPV of 99%. The differences between the various studies probably depend on the different case-mix investigated in terms of micro- and macroalbuminuric patients. As a whole, our study on diabetics confirms findings reported by others, i.e. that the Clinitek Microalbumin test is valuable particularly in checking for the absence of microalbuminuria (the NPV in our diabetic group was 98%).

Results obtained in the general population also support this conclusion. The strip's sensitivity in detecting an ACR >3.4 mg/mmol (90%), combined with the high NPV (99%), makes this test especially useful for screening CKD in the general population where a negative result that rules out CKD is much more important than a correct diagnosis of CKD. The likelihood of a person testing negative with the strip while having an ACR >3.4 mg/mmol as determined by immunonephelometry is <1.8%, given the prevalence of ~7% of ACR >3.4 mg/mmol in the INCIPE population (manuscript in preparation). Using the strip test enabled us to avoid the laboratory test for 83% of our subjects, so screening with the dry ACR chemistry test and confirming positive results with laboratory tests seems to be a very efficient strategy.

In a population with a high prevalence of albuminuria like the diabetics, the strip test for albumin seems to be superior to the ACR strip, particularly in terms of PPV (83% versus 71%), confirming previous results [19–21]. In contrast, in the general population, though modestly, the ACR strip test seems to perform better than the albumin strip with a higher concordance index (91% versus 86%) and NPV (99% versus 98%). The advantage of the ACR strip versus the albumin strip in terms of detection of negative samples for albuminuria was remarkable, which in the general population would save the laboratory test for 9% more of subjects.

We were unable to find an explanation for the false-positive and false-negative cases, since the samples did not reveal any particular physico-chemical characteristic. It does not seem to depend on how close the value is to the cut-offs for detection since the false-negative samples and the false-positive results cover a quite large interval of values.

In terms of precision, our findings confirm previously reported results [12].

A decrease in the albumin concentration in samples frozen at –20°C and stability at –80°C has already been reported [15,21–26]. In a study on urine samples stored for 2 years at –20°C, Brinkman et al. observed a reduction starting beyond 5 months of storage, particularly in samples with albumin concentration <80 mg/L [22]. The same authors have also reported that the albumin concentration in urine is stable after 1-year storage at –80°C [23]. In a recent study that investigated the stability of urinary albumin over a 2.5-year storage at –70°C, a modest 1.5% 6-month decrease in albumin concentrations was shown [24]. Such a decrease presumably affected phenotype classification only after longer conservation [24]. In reference to urinary creatinine levels, both a minimal effect and no effect at all have been reported after prolonged storage at –70°C [24–26]. However, all these studies dealt with wet chemistry methods, while to the best of our knowledge no study reported on the effect of urine storage on the performance of dry chemistry methods for albumin and creatinine, and namely on the Clinitek Microalbumin strip. In the present study, we show that the Clinitek Microalbumin strip can be used as a screening test to assess increased albumin excretion in the general population on long-term –80°C frozen samples, saving expensive quantitative measurements for a significant number of subjects (>93% of the population).

In conclusion, we can confirm the good analytical performance of the strip test (good sensitivity and specificity, no interferences, excellent precision). Given its excellent NPV, the Clinitek Microalbumin test is an efficient method for screening the general population for microalbuminuria: since the prevalence of the condition is low, this approach offers the advantage of making it unnecessary to process large numbers of samples using the more laborious laboratory methods.



   Acknowledgments
 
The strips and the instrument used in the study were kindly provided by Siemens Medical Solutions Diagnostics. The study obtained the approval of the institutional Ethics Committee.

Conflict of interest Statement. None declared.



   References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. El Nahas AM, Bello AK. Chronic kidney disease: the global challenge. Lancet (2005) 365:331–340.[Web of Science][Medline]
  2. Kausz AT, Khan SS, Abichandani R, et al. Management of patients with chronic renal insufficiency in the Northeastern United States. J Am Soc Nephrol (2001) 12:1501–1507.[Abstract/Free Full Text]
  3. Coresh J, Astor BC, Green T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population. Third National Health and Nutrition Examination Survey. Am J Kidney Dis (2003) 41:1–12.[Web of Science][Medline]
  4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis (2002) 39:S1–S266.[CrossRef][Web of Science][Medline]
  5. American Diabetes Association. Clinical practice recommendation 2007. Nephropathy screening and treatment. Diabetes Care (2007) 30:S79–S81.[CrossRef]
  6. Sarafidis PA, Bakris GL. Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease. Nephrol Dial Transplant (2006) 21:2366–2374.[Free Full Text]
  7. Forman JP, Brenner BM. Hypertension and microalbuminuria: the bell tolls for thee. Kidney Int (2006) 69:22–28.[CrossRef][Web of Science][Medline]
  8. Romundstad S, Holmen J, Kvenild K, et al. Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trondelag Health Study (HUNT), Norway. Am J Kidney Dis (2003) 42:466–473.[CrossRef][Web of Science][Medline]
  9. Verhave JC, Gansevoort RT, Hillege HL, et al. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int (2004) 66(Suppl_92):18–21.
  10. Gambaro G, D’Angelo A, Conte M, et al. Silent chronic kidney disease epidemic seen from Europe: designing strategies for clinical management of the early stages. J Nephrol (2005) 18:123–135.[CrossRef][Web of Science][Medline]
  11. Sarafidis PA, Riechie J, Bogojevic Z, et al. A comparative evaluation of various methods for microalbuminuria screening. Am J Nephrol (2008) 28:324–329.[CrossRef][Web of Science][Medline]
  12. Parsons M, Newman DJ, Pugia M, et al. Performance of a reagent strip device for quantitation of the urine albumin:creatinine ratio in a point of care setting. Clin Nephrol (1999) 51:220–227.[Web of Science][Medline]
  13. Le Floch JP, Marre M, Rodier M, et al. Interest of Clinitek Microalbumin in screening for microalbuminuria: results of a multicenter study in 302 diabetic patients. Diabetes Metab (2001) 27:36–39.[Web of Science][Medline]
  14. Pugia MJ, Lott JA, Profitt JA, et al. High-sensitivity dye binding assay for albumin in urine. J Clin Lab Anal (1999) 13:180–187.[CrossRef][Web of Science][Medline]
  15. Pugia MJ, Lott JA, Wallace JF, et al. Assay of creatinine using the peroxidase activity of copper–creatinine complexes. Clin Biochem (2000) 33:63–70.[CrossRef][Web of Science][Medline]
  16. American Diabetes Association. Position statement. Nephropathy in diabetes. Diabetes Care (2004) 27:79–83.[CrossRef]
  17. Pugia MJ, Lott JA, Clark LW, et al. Comparison of urine dipsticks with quantitative methods for microalbuminuria. Eur J Clin Chem Clin Biochem (1997) 35:693–700.[Web of Science][Medline]
  18. Croal BL, Mutch WJ, Clark BM, et al. The clinical application of a urine albumin:creatinine ratio point-of-care device. Clin Chim Acta (2001) 307:15–21.[CrossRef][Web of Science][Medline]
  19. Meinhardt U, Ammann RA, Flück C, et al. Microalbuminuria in diabetes mellitus: efficacy of a new screening method in comparison with timed overnight urine collection. J Diabetes Complications (2003) 17:254–257.[CrossRef][Web of Science][Medline]
  20. Lum G. How effective are screening tests for microalbuminuria in random urine specimens? Ann Clin Lab Sci (2000) 30:406–411.[Abstract]
  21. Hara F, Nakazato K, Shiba K, et al. Studies of diabetic nephropathy. I. Effects of storage time and temperature on microalbuminuria. Biol Pharm Bull (1994) 17:1241–1245.[Web of Science][Medline]
  22. Brinkman JW, de Zeeuw D, Duker JJ, et al. Falsely low urinary albumin concentration after prolonged frozen storage of urine samples. Clin Chem (2005) 51:2181–2183.[Free Full Text]
  23. Brinkman JW, de Zeeuw D, Lambers Heerspink HJ, et al. Apparent loss of urinary albumin during long-term frozen storage: HPLC versus immunonephelometry. Clin Chem (2007) 53:1520–1526.[Abstract/Free Full Text]
  24. Parekh RS, Kao WH, Meoni LA, et al. Reliability of urinary albumin, total protein, and creatinine assays after prolonged storage: the family investigation of nephropathy and diabetes. Clin J Am Soc Nephrol (2007) 2:1156–1162.[Abstract/Free Full Text]
  25. Schultz CJ, Dalton RN, Turner C, et al, The Oxford Regional Prospective Study Group. Freezing method affects the concentration and variability of urine proteins and the interpretation of data on microalbuminuria. Diabet Med (2000) 17:7–14.[CrossRef][Web of Science][Medline]
  26. Berg KJ, Kristoffersen DT, Djøseland O, et al. Reference range of some enzymes and proteins in untimed overnight urine and their stability after freezing. Clin Chim Acta (1998) 272:225–230.[CrossRef][Web of Science][Medline]
Received for publication: 5. 6.08
Accepted in revised form: 23.10.08


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