American Association for Clinical Chemistry
Better health through laboratory medicine
January 2011 Clinical Laboratory News: Diagnostic Profiles


Diagnostic Profiles

Population-based Screening for Chronic Kidney Disease Is not Cost-Effective

New research indicates that population-based screening for chronic kidney disease (CKD) is not cost-effective overall or in subgroups of people with hypertension and the elderly (BMJ 2010;341:c5869). However, the investigators found that targeted screening of diabetics would yield an acceptable cost per quality adjusted life years (QALY).

The Canadian-based authors wanted to explore the value of population-based screening for CKD because CKD and end stage renal disease (ESRD) are emerging public health problems with negative clinical consequences leading to poor quality of life and high healthcare costs. In addition, CKD—defined as glomerular filtration rate (GFR) <60 ml/min/1.73 m2—often is not detected until the disease is advanced, thereby suggesting a role for early screening. Prior studies of this nature relied on urinalysis results to determine the effectiveness of screening, but in this instance, the authors used estimated GFR (eGFR). Their objective was to compare the incremental cost utility of population-based screening using eGFR versus not screening the same population.

The researchers developed a Markov decision analytic model to simulate the effect of several different disease states in both the screening and no-screening populations. They gathered CKD prevalence data from the National Health and Nutrition Examination Survey III and data from 290,613 individuals in the Alberta Kidney Disease Network to obtain information about healthcare resource use, outcomes, and diagnostic test results.

Using a variety of assumptions and sensitivity and scenario analyses, the researchers determined that compared with no screening, a population-based screening strategy for CKD would have an incremental cost of $C463 (US $382) and a gain of 0.0044 QALYs per patient, representing a cost per QALY gained of $C104,900. In a cohort of 100,000 people, screening would reduce the number of people developing ESRD from 675 to 657. In contrast, the estimated cost per QALY in diabetics would be $572,000, and researchers calculated that in a cohort of 100,000 people with diabetes, screening would reduce the number of people who develop ESRD from 1,796 to 1,741.

The authors concluded that although CKD is prevalent, especially in the elderly, most people who would be identified through population-based screening likely would have non-proteinuric CKD, relatively slow loss of kidney function, and limited benefit from angiotensin blocker therapy, making this strategy not worthwhile. 

Serum Uric Acid Predicts Progression Of Coronary Artery Disease

University of Colorado researchers recently reported findings that serum uric acid (UA) levels predict progression of coronary artery calcification (CAC) independently of other established cardiovascular disease (CVD) risk factors (Diabetes Care 2010:33;2471–3). While previous studies have associated increased UA levels with mortality and negative cardiovascular outcomes in both the general population and type 2 diabetics, this study is the first to report an independent association of UA levels to the progression of coronary atherosclerosis, according to the authors.

The researchers defined normoalbuminuria as overnight albumin excretion rate ≤20 µg/min or urinary albumin-to-creatinine ratio ≤30 mg/g. They used the Mayo Clinic Quadratic Equation to estimate glomerular filtration rate, and performed stepwise multiple regression analysis to select predictors of CAC progression.

The researchers found that in patients without renal disease, serum UA predicted CAC progression independent of conventional cardiovascular risk factors, including diabetes and the presence of metabolic syndrome, with an odds ratio of 1.3. In subjects with pre-existing chronic kidney disease, UA did not predict CAC.

Based on their findings, the authors suggest that serum UA levels should be considered a marker of increased coronary artery disease risk in both diabetics and non-diabetics who do not have significant kidney disease.

Gene Expression Algorithm Adds to Coronary Artery Disease Staging

New research indicates that a blood-based gene expression algorithm for determining the likelihood of obstructive coronary artery disease (CAD) in nondiabetic patients provides a statistically significant but modest improvement in the classification of patients compared with clinical factors or noninvasive imaging (Ann Intern Med 2010;153:425–34). This multicenter prospective trial validated the utility of the algorithm, which is based on expression of 23 genes, age, and sex.

The study involved 526 patients referred for coronary angiography with a history of chest pain, suspected angina-equivalent symptoms, high risk for CAD, and no history of myocardial infarction, revascularization, or obstructive CAD. Blood samples were taken prior to angiography, and gene expression was measured using polymerase chain reaction assays. The algorithm clustered the genes into six terms involved in neutrophil activation and apoptosis, neutrophil activation-lymphocyte ratio, NK activation-T-cell ratio, and B-T-cell ratio and adaptive immune response. Four of the terms are sex-independent and two are sex-specific.

The researchers used a series of logistic regression models to compare the gene expression algorithm score alone and in combination with other variables, against clinical model scores. The primary endpoint, area under the receiver-operating characteristic curve, was 0.70. The test improved net reclassification over both a risk score method and an expanded clinical model. At a score threshold that corresponded to a 20% likelihood of obstructive CAD, the sensitivity and specificity were 85% and 43%, respectively, with negative and positive predictive values of 83% and 46%, respectively. 

Repeat PCR Testing for C. difficile not Necessary

Stanford University researchers have found that repeat polymerase chain reaction (PCR) testing targeting the tcdB toxin B gene of Clostridium difficile rarely is useful (J Clin Microbiol 2010;48:3738–41). Repeating C. difficile tcdB PCR within 14 days of a previous negative result “yields little relevant clinical data, other than confirming the negative result of the initial test, in an overwhelming majority of tests,” they wrote. However, the authors suggested that repeat PCR testing, especially 7–14 days after a negative result, “can be useful in a small subset of patients with high clinical suspicion for infection.”

The authors conducted the study because they noticed that physicians were ordering duplicate or triplicate tcdB PCR, similar to the ordering patterns for cell culture cytotoxicity assay or enzyme immunoassay testing. They wanted to explore the clinical utility of this repeat testing within 14 days of a negative result and determine when repeat testing might be warranted.

The study included stool samples from 1,287 patients who had diarrhea, and were at least 1 year old. Of all the tests, 461 were repeat tests for patients who already had at least one PCR result within the last 14 days. Of these 461 tests, 406 were from patients with a prior negative result. Only 10 (2.5%) of the 406 repeat tests turned positive, and only one of these turned out to be false positive. The remaining nine patients for whom PCR results converted from negative to positive had multiple risk factors for C. difficile infection, such as current hospitalization, a history of severe underlying disease, and ongoing antibiotic treatment.