Dewey C. Scheid, MD, MPH Laine H. McCarthy, MLIS Frank H. Lawler, MD, MSPH Robert M. Hamm, PhD Kathryn E.H. Reilly, MD, MPH Oklahoma City, Oklahoma Submitted, revised, April 16, 2001. From the Department of Family and Preventive Medicine, University of Oklahoma Health Sciences Center. Reprint requests should be addressed to Laine H. McCarthy, 900 NE 10th Street, Oklahoma City, OK 73104. E-mail: laine-mccarthy@ouhsc.edu.
References
The quality of the screening articles was graded by a consensus of 2 reviewers using published criteria.15 Studies that presented sufficient information were examined to determine if the test characteristics could be pooled to give summary point estimates.16 We attempted to combine sensitivities and specificities reported for: (1) quantitative tests with a cutoff UAC of 20 mg per L or greater, (2) the same semiquantitative test used with any type of urine sample, or (3) the same semiquantitative test used with 1 type of urine sample. Using the chi-square test, we tested homogeneity among the sensitivities and specificities reported in the each of the studies. Studies were considered homogeneous if P was .05 or greater. Confidence intervals were calculated using the normal approximation to the binomial method.17
MA screening recommendations were analyzed using the criteria of Frame and Carlson18 and that of the US Preventive Services Task Force for determining effectiveness.19 The impact that repeated testing strategy recommended by the ADA8 had on diagnostic accuracy was analyzed using a clinical decision-making calculator.20 The positive predictive value (PPV) was calculated by specifying the probability of “true MA,” the sensitivity and specificity of the MA test, and simultaneously varying both the phi coefficients (for cases with “true” MA and without MA) from 0 (independence) to 1 (dependence). The phi coefficient is a measure of the correlation between the dichotomous results of 2 tests in the presence or absence of the target condition. Cost-effectiveness analyses were assessed with the quality checklist of 37 critical features developed by Gold and colleagues.21
Results
Literature Yield
We retrieved 105 articles from the initial literature search and excluded 44 general review articles. The reference lists of the remaining 61 articles were reviewed to locate additional relevant articles. No controlled trials of screening to prevent progression to nephropathy or that compared sequential repeated screening strategies were identified. We found 31 articles that reported the performance of 1 MA screening test or more. Of these, 8 reported the characteristics of a quantitative test;22-29 22 reported the characteristics of a semiquantitative test;28,30-50 and 1 reported both.28 Our review is unlikely to be affected by publication bias, because a wide range of results were reported from varied international sources.
We used a variety of cutoffs in the studies that reported quantitative UAC or UACR, which precluded pooling test characteristics of most of these studies. Because of the striking heterogeneity among studies and the existence of at least 1 large study for the 2 most commonly studied semiquantitative tests, we did not pool the sensitivities and specificities. The sensitivity ranged from 56% to 100% and specificity from -81% to 98% for UAC of 20 mg per L or greater for quantitative tests Table 1. For morning urine samples, the pooled sensitivity was 75% (95% confidence interval [CI], 59-91) and the pooled specificity was 97% (95% CI, 94-99).23,26 Test performance was similar for all types of urine samples.
The sensitivity ranged from 51% to 100% and specificity from 21% to 100% for semiquantitative tests. Test performance was similar for all types of urine samples. Micral (Roche; Mannheim, Germany) was the most extensively reported semiquantitative test. A large (n=2228) multicenter study of the Micral II found a sensitivity of 96.7% and specificity of 71% to detect a UAC of 20 mg per L or greater by radioimmunoassay (RIA).42 The sensitivity of the Micro-Bumintest (Bayer; Pittsburgh, Pa) ranged from 60% to 100% and the specificity from 21% to 97%. A large (n=1186) population-based study of the Micro-Bumintest reported a sensitivity of 98.6% (95% CI, 97.5-99.6) and specificity of 85.1% (95% CI, 82.4-87.7) to detect a UAC of 30 mg per L or greater by RIA.48
There is often considerable interobserver variation in the evaluation of semiquantitative tests that involve colorimetric changes. Mogenson and colleagues42 found 93% concordance of Micral results from 538 samples. The sensitivity of the Micral varies when used by different operators: general practitioners, 66%; laboratory technicians, 91%; and trained nurses, 84%. Ten percent of physicians who were less familiar with procedures accounted for 44% of the misread strips.34 The Micral was not influenced by most potential interference factors,51 though it may be affected by freezing.38,40 Authors have reported high numbers of false positives47 and problems interpreting the results of the Micro-Bumintest tests.52,53
Frame and Carlson Criteria for Screening Tests
The 6 criteria of Frame and Carlson18 we applied to MA screening Table 2 were introduced in 1975. There is adequate evidence to suggest that screening for MA meets the first 4 criteria.4,54,55 Whether the test is acceptable to patients at a reasonable cost (criterion 5) and is cost-effective (criterion 6) is less certain.
