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
OBJECTIVE: Our goal was to evaluate whether screening patients with diabetes for microalbuminuria (MA) is effective according to the criteria developed by Frame and Carlson and those of the US Preventive Services Task Force.
STUDY DESIGN: We searched the MEDLINE database (1966-present) and bibliographies of relevant articles.
OUTCOMES MEASURED: We evaluated the impact of MA screening using published criteria for periodic health screening tests. The effect of the correlation between repeated tests on the accuracy of a currently recommended testing strategy was analyzed.
RESULTS: Quantitative tests have reported sensitivities from 56% to 100% and specificities from 81% to 98%. Semiquantitative tests for MA have reported sensitivities from 51% to 100% and specificities from 21% to 100%. First morning, morning, or random urine sampling appear feasible. Assuming an individual test sensitivity of 90%, a specificity of 90%, and a 10% prevalence of MA, the correlation between tests would have to be lower than 0.1 to achieve a positive predictive value for repeated testing of 75%.
CONCLUSIONS: Screening for MA meets only 4 of 6 Frame and Carlson criteria for evaluating screening tests. The recommended strategies to overcome diagnostic uncertainty by using repeated testing are based on expert opinion, are difficult to follow in primary care settings, do not improve diagnostic accuracy sufficiently, and have not been tested in a controlled trial. Although not advocated by the American Diabetes Association, semiquantitative MA screening tests using random urine sampling have acceptable accuracy but may not be reliable in all settings.
Six major reviews of the natural history, prevention, and treatment of diabetic nephropathy have been published.1-6 Key points of these overviews with regard to screening are that persistent microalbuminuria (MA) is a reliable marker for the presence of diabetic nephropathy in both patients with type 1 (insulin-dependent) and type 2 (non–insulin-dependent) diabetes mellitus, and that angiotensin-converting enzyme inhibitors (ACEIs) slow or prevent the progression of diabetic nephropathy in patients with MA. The latter benefit occurs in both patients with type 1 and type 2 diabetes and appears to be long-lasting.
At least 6 sets of recommendations7-13 that advocate routine MA screening in all patients with diabetes have been issued by various physicians’ groups and organizations. Current American Diabetes Association (ADA) guidelines permit 3 types of collection to measure urinary albumin excretion (UAE): 24-hour (<30 mg/24 hrs), timed (<20 mg/minute), and untimed random albumin/creatinine ratio (UACR, <30 mg/mg creatine),*Table 1w7,8 Dipstick semiquantitative rapid tests are included in the ADA guidelines as alternatives if quantitative assays are not readily available, but they must be confirmed by quantitative methods. Others have suggested that semiquantitative tests should not be considered substitutes for the other methods.4 The variability of UAE is considered too high to use urine albumin concentration (UAC) alone. The average intraindividual daily UAE variation is approximately 40%; standing, exercise, illness, and diuresis all increase UAE.14 Because of this variation, the ADA guidelines recommend that 2 of 3 tests (performed over a 3- to 6-month period) should provide elevated results before the patient is considered to have MA.7,8
Recommended strategies to overcome diagnostic uncertainty by repeated testing are difficult to follow in primary care settings and do not appear to improve diagnostic accuracy. Published recommendations are based on expert opinion regarding the performance of MA tests. However, no controlled trial of the effectiveness of MA screening has been reported.3 Although concern about diagnostic uncertainty has led to recommendations for repeated testing and the use of timed quantitative MA tests, these strategies may be difficult to follow in primary care settings and may not improve accuracy. With this systematic review we critically examined components of previous recommendations and addressed the question of whether persons with diabetes should be screened for MA.
Methods
We searched the MEDLINE database from 1966 to the present looking for studies describing diagnostic tests for MA. The search strategy included the medical subject headings “albuminuria” and “diabetes mellitus” and the text words “microalbuminuria,” “nephropathy or nephropathies,” and “screening or testing or diagnosis.” The reference lists of relevant articles and the 6 major review articles1-6 were searched by hand to locate additional pertinent articles. A second search following identical procedures was performed substituting “cost-benefit analysis” for “screening or testing or diagnosis.” Screening articles were included if: (1) the subjects were only patients with diabetes, (2) the studies investigated the use of untimed urine samples (first morning [FAM], morning [AM], random urine sampling [RUS]), (3) tests were performed only in an ambulatory setting, and (4) test performance (sensitivity and specificity) could be determined from the article. Though it was not recommended in the ADA guidelines, we included semiquantitative tests as possible alternatives, because these tests are in clinical use and have been extensively studied. We initially included articles if any 1 of the 4 reviewers thought they met the inclusion criteria. Articles considered relevant by 3 of the 4 reviewers were included in the final round. Only English language articles reporting studies in human beings were selected. We did not seek unpublished data.
