Cost-Effectiveness of Two Screening Programs for Microalbuminuria in Type 2 Diabetes

The presence of microalbuminuria is associated with an increased risk for developing nephropathy and cardiovascular diseases in both type 1 and type 2 diabetes (1,2,3). A proper pharmacological treatment can reduce urinary albumin excretion rate (AER) and prevent clinical nephropathy. Consequently, the screening for microalbuminuria should be an essential tool of the care for diabetic patients.

Controversy still exists regarding the type of urine specimen to be used to evaluate microalbuminuria. AER determined in timed urine collections (24 h or overnight) is the most direct measure of urinary albumin excretion (4,5). However, due to the demand of the protocol and frequent imperfect patient adherence, the AER is not practical for epidemiological studies or clinical settings. For these reasons, the measurement of the albumin-to-creatinine ratio (ACR) in a random spot urine has became a widely accepted clinical tool for assessing urinary albumin excretion (6,7,8). Recently, several semiquantitative office tests for detecting abnormal albuminuria have been developed (9).

The aim of our study was to identify the easiest and most cost-effective screening program for microalbuminuria in an outpatient clinic. We evaluated specificity, sensitivity, and positive (PPV) and negative (NPV) predictive values of measurement of microalbuminuria by using ACR or by an immunological semiquantitative test in a first-morning spot urine sample in comparison with AER measured in three timed overnight urine collections.

Urinary albumin concentration was determined by using an immunological semiquantitative test (Micral-test; Roche Diagnostics, Mannheim, Germany) and the ACR by using DCA 2000 Analyzer (Bayer, München, Germany) in a first-morning urine specimen of 1,712 type 2 diabetic patients consecutively admitted to our outpatient clinic. AER was then measured using three timed overnight urine collections that were performed at home a month after the screening evaluation. Albuminuria was detected by immunoturbidimetric method (Image; Beckman). Sensitivity, specificity, PPV, and NPV were calculated to determine the diagnostic properties of Micral and ACR. The AER, calculated as the median of three timed overnight urine collections, was used as the reference indicator. Microalbuminuria was defined as Micral-test ≥20 mg/l or ACR >2.8 g/mol for women and >1.9 g/mol for men (10) or AER between 20 and 200 μg/min. Patients with urinary tract infections, acetonuria, hematuria, or leucocituria (n = 56) were excluded from the study.

In the remaining 1,656 patients eligible for evaluation, the median of AER revealed that 1,273 patients were normoalbuminuric (76.8%), 338 microalbuminuric (20.4%) and 45 macroalbuminuric (2.7%). These figures are similar to those already found in an Italian population (11). Macroalbuminuric patients were excluded from the subsequent analysis.

Of the remaining 1,611 patients, 516 patients were classified as microalbuminuric by using Micral-test (194 false-positive test results and 16 false-negative tests compared with the AER method). According to the ACR, 420 patients were microalbuminuric (95 false-positive tests and 13 false-negative tests). The correlation coefficient between ACR and AER levels was 0.858.

For the Micral-test, a sensitivity of 95.2%, a specificity of 84.7%, a PPV of 62.4%, and a NPV of 98.5% were calculated; for the ACR, a sensitivity of 96.1%, a specificity of 92.5%, a PPV of 77.3%, and an NPV of 98.9% were found.

Although the semiquantitative measurement (Micral-test) and ACR measurement in a first-morning urine specimen were easy methods, acceptable for patients, and convenient to be carried out in an office setting because of a fast reading time, both determinations had a very high sensitivity but a lower specificity. Particularly, 194 of 516 patients with Micral ≥20 mg/l were determined to be normoalbuminuric with AER; 95 of 420 patients who were determined to be microalbuminuric with ACR were considered normoalbuminuric with AER. Although the use of ACR reduces the influence of variations in urinary flow rate, it is considerably more expensive than Micral-test (4.64 vs. 1.54 per test), because the former needs the additional measurement of creatinine at the expense of extra costs. In our population, an initial screening to identify microalbuminuric patients carried out with ACR rather than Micral-test would have determined a much higher final cost (7,684 vs. 2,250). However, this extra cost could still be acceptable if the results obtained were comparable to those found with a standard measurement of AER in a timed urine collection. Although in the past decade numerous reports evaluated the use of ACR in first-morning specimens as an alternative to AER (12), in our study, compared with AER, the good sensitivity of ACR (96.1%) was associated with a PPV of only 77.3%. Therefore, by using the determination of ACR rather than AER in our population to identify patients with microalbuminuria, ∼6% of our normoalbuminuric type 2 diabetic patients would have received an inappropriate therapeutic intervention for microalbuminuria. On the other hand it remains to be established whether a repeated determination of ACR as for AER (in three first-morning spot urine samples) would have improved the specificity of ACR, thereby reducing the percentage of false-positive tests.

In conclusion, our results demonstrate that the detection of urinary albumin concentration in a first-morning urine sample by a semiquantitative test (Micral) is the easiest and most cost-effective screening procedure to identify microalbuminuric subjects in an outpatient type 2 diabetic population. The ACR, because of its low PPV, cannot substitute the determination of AER in timed overnight urine collections for the confirmation and the initiation of a therapeutic intervention for microalbuminuria in type 2 diabetic patients.