Keywords
hypertension, albuminuria, urine dipstick, diagnostic test
hypertension, albuminuria, urine dipstick, diagnostic test
The 2nd version of the manuscript provided additional information in the method section for better clarity. Furthermore, a reference was revised.
See the authors' detailed response to the review by Surendran Deepanjali
See the authors' detailed response to the review by Polathep Vichitkunakorn
Strong evidence has indicated that the presence of albuminuria in hypertensive patients is associated with the development of chronic kidney disease (CKD), which increases the risk of cardiovascular-related morbidity and mortality1,2. Early detection of CKD is important as either angiotensin-converting-enzyme inhibitor drugs or angiotensin II receptor blocker drugs can be added to a patient’s treatment regimen to slow down the progress of the disease and thus reduce all-cause mortality.
Detection of albumin in urine plays an important role in diagnosing CKD in the early stages. Regarding the detection of albumin in urine, urine albumin-to-creatinine ratio (ACR) has widely been recommended to be used in diagnosing albuminuria, which is defined as the amount of urine albumin divided by urine creatinine ≥ 30 mg/g [≥ 3 mg/mmol]3,4.
Despite the recommendations, performing ACR in all patients with hypertension is not always applicable, particularly in a primary care unit in rural or outreach areas where the necessitated resources may be unavailable. Practically, the urine dipstick is a test that has widely been used to identify the presence of albumin in the urine due to its low cost and high accessibility.
Although using the urine dipstick is pragmatic, existing literature has not affirmed the accuracy of the test. Previous research has revealed a variety of diagnostic accuracy of the urine dipstick, compared with ACR. While some studies suggest that the dipstick is inappropriate for screening albuminuria5–8, others conclude that trace albuminuria from a dipstick can be used to indicate the presence of urine albumin9,10.
Owing to result inconsistencies, it is still arbitrary as to whether or not positive findings of albumin from a urine dipstick could be used to confirm presence of albuminuria. Additionally, there is as yet no evidence to demonstrate if diagnostic results would be consistent across populations. Therefore, this study aimed to assess the diagnostic accuracy of a dipstick in Thai hypertensive patients for detecting albuminuria.
This analysis is based on retrospective data from patients who visited Lampang Hospital from January to December 2018. The study included patients aged 18 years and over who were diagnosed with hypertension, ICD10 code “I10-14”, with the results of urine dipstick and ACR from random single spot urine being examined in the same day at least once. Laboratory results from the last visit were used if multiple results of a urine dipstick and ACR on the same day were presented within the same patient. Patients with the urine results containing white blood cell more than 5-10 cells per high power field were suspected of having urinary tract infections, and thus were excluded from the study.
This study protocol was approved by the Ethics Committee at Lampang Hospital (No.79/62). Consent of the patients to use their data in the study was waived by the ethical committee due to the retrospective nature of the study.
ACR was a reference standard to indicate the level of urine albumin. Evaluation of ACR was performed at Lampang Hospital using the immunoturbidimetric essay by AU5800/DxC700AU. The result of ACR ≥30 mg/g indicates the presence of albuminuria11,12.
This study employed the urine dipstick, “URiSCAN 9 SG” and the analyzer “URiSCAN SUPER+”, as an index test. Interpretation of the results were based on the color changes on the indicator tetrabromophenol blue in the presence of urine albumin. A positive reaction is indicated by a color change to yellow or green, reflecting the albumin results of negative, trace, 1+, 2+,3+, and 4+.
Demographic characteristics including age and sex were collected for use in the analysis. Body mass index was calculated by weight in kilograms divided by squared height in centimeters13. Glomerular filtration rate (GFR) was estimated using the formula eGFR = 141 × min(SCr/κ, 1)α × max(SCr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if Black]14. Information about patients’ underlying disease of diabetes was obtained from the diagnosis in the hospital’s electronic medical record with ICD10 code “E10-14”15.
Chi-squared test and t-test were applied to explore the association between the presence of albuminuria from ACR and covariates, with a significance level of 0.05. Sensitivity, specificity, positive predictive value, and negative predictive value of the dipstick were calculated, with 95% confidence intervals. The area under the receiver operating characteristic curve was approximated to demonstrate the test performance16. Subgroup analyses using the trace threshold of dipstick were performed to elucidate the diagnostic accuracy of the test among subgroups. Statistical analyses were performed using STATA version 1317.
A total of 3,067 hypertensive patients matched the study criteria and were included in the analysis (Table 1). Approximately 39.8% of the samples presented with albuminuria. The mean age of the patients was 63.7 year, with ~40% being men. Diabetes appeared among 73.7% of the patients; 17.7% of them had eGFR <60 ml/min/1.73m2. Albuminuria was present in 24.5% of those with negative result from the dipsticks. Distribution of albumin-creatinine ratios with respect to results of urine dipsticks were exhibited in Figure 1.
Table 2 demonstrated the sensitivity, specificity, positive and negative predictive values of urine dipstick in detecting albuminuria. It is seen that sensitivity of 53.6% was observed when the trace threshold was applied, whereas cutoff of ≥2+ and higher yields 100% test specificity. The area under the receiver operating characteristic curve was 0.7482 (Figure 2).
Comparing diagnostic accuracy of the dipstick, it appears that sensitivity, specificity, along with positive and negative predictive values were approximately the same in all subgroups (Table 3).
Existing studies have manifested a wide range of positive predictive values (PPVs) of urine dipsticks among patients with hypertension, ranging from 27 to 826,18. However, none have been conducted in a Thai population. Results of this study, exploring the diagnostic accuracy of the dipstick in a Thai population, not only illustrates the outcomes in this specific population, but can also be used in comparison with results from other populations for a better understanding of test accuracy.
Previous research has documented the differences in sensitivity and specificity of the dipstick across populations. A Japanese study showed sensitivity, specificity, and PPV of 37.1%, 97.3%, and 71.4%, respectively10. Another study conducted in Australian adults showed sensitivity, specificity, and PPV of 69.4%, 86.8%, and 27.1%, respectively6. One possible explanation for the difference in diagnostic accuracy of the dipstick was owing to differences in the characteristics of the populations7. The other study points out variation in the calibration of the dipstick as another explanation for differences between populations8. Compared with previous reports, diagnostic parameters shown in this study affirms variation in diagnostic performance of the dipstick across populations. This implies that the assessment of dipstick performance should be recommended for different populations.
It should be noted that false positive results of the dipstick could come from highly alkaline urine and contamination of antiseptics. Moreover, urine specimens used in this study came from random spot urine collection, which may be subjected to false positive results. Likewise, false negative results may have occurred due to excessive hydration before collecting the urine specimen, which leads to a decrease in concentration of urine albumin and subsequently a smaller chance of detecting albuminuria.
Such low sensitivity of 53% from the urine dipstick indicates that almost half of the patients with albuminuria cannot be identified using just the urine dipstick. It is also seen that among patients with a negative albumin result from the dipstick, albuminuria was found in nearly a quarter of them. This outcome well aligns with previous studies asserting low sensitivity of the dipstick in detecting albuminuria5,8,10. Given strong evidence indicating the high probability of cases being undetected, using the dipstick alone should not be recommended for use in screening of albuminuria among hypertensive patients.
Results from the study revealed a rather high predictability of the dipstick in detecting urine albumin. Concerning the dipstick cutoffs, applying the trace threshold yields a PPV of 86.5%, compared with 98.2% and 100% using the 1+ and 2+ thresholds, respectively. Though a rather high chance of predicting albuminuria once hypertensive patients have these results of trace or higher from the dipstick, it should be borne in mind that albuminuria may be overly diagnosed with the application of the trace threshold, compared with using the higher cutoffs.
Although excellent PPV can be achieved when employing higher thresholds of the dipstick, drawbacks remain when the recommendation for using the high threshold is applied due to fewer patients being applicable. Considering the trade-off between PPV and applicability of the dipstick results, the trace threshold may be recommended for indicating the presence of albuminuria in hypertensive patients.
Even though the KDIGO guidelines3 have recommended the use of ACR to indicate the presence of albuminuria, this is proven to be rather costly and not readily available in some regions. Limitations, regarding the availability and costs of ACR, may arise when considering the application of ACR for routine screening of hypertensive patients. Nonetheless, evidence has demonstrated a low sensitivity of urine dipsticks, which should not be recommended for screening albuminuria. Hence, ACR is deemed the option for screening albuminuria in the setting where resources are available.
While existing evidence is controversial to whether the urine dipstick should be recommended for screening albuminuria in hypertensive patients, results from this study demonstrated that the dipstick has such low sensitivity in detecting albumin in urine in the Thai population. These results suggest that the urine dipstick not be recommended for screening urine albumin in patients with hypertension. In contrast, results of trace or higher yields high PPV, indicates a very high possibility of the presence of microalbuminuria.
Figshare: Diagnostic Accuracy of a Urine Dipstick for Detecting Albuminuria in Hypertensive Patients, http://www.doi.org/10.6084/m9.figshare.1265171619.
Figshare: STARD checklist for "Diagnostic Accuracy of a Urine Dipstick for Detecting Albuminuria in Hypertensive Patients", http://doi.org/10.6084/m9.figshare.1267315420.
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
The authors would like to thank Dr.Thanawat Vongchaiudomchoke, nephrologist, and Dr.Napat Phetkub for their valuable comments.
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Is the work clearly and accurately presented and does it cite the current literature?
Yes
Is the study design appropriate and is the work technically sound?
Yes
Are sufficient details of methods and analysis provided to allow replication by others?
Yes
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Partly
Are the conclusions drawn adequately supported by the results?
Yes
Competing Interests: No competing interests were disclosed.
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: urinary tract infections, medical philosophy
Competing Interests: No competing interests were disclosed.
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: urinary tract infections, medical philosophy
Is the work clearly and accurately presented and does it cite the current literature?
Yes
Is the study design appropriate and is the work technically sound?
Yes
Are sufficient details of methods and analysis provided to allow replication by others?
Yes
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Partly
Are the conclusions drawn adequately supported by the results?
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Epidemiology
Is the work clearly and accurately presented and does it cite the current literature?
Partly
Is the study design appropriate and is the work technically sound?
Yes
Are sufficient details of methods and analysis provided to allow replication by others?
Yes
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Partly
Are the conclusions drawn adequately supported by the results?
Partly
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: urinary tract infections, medical philosophy
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Version 2 (revision) 07 Jul 21 |
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Version 1 15 Oct 20 |
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