American Association for Clinical Chemistry
Better health through laboratory medicine
June 2009 Clinical Laboratory News: Diagnostics Profiles

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June 2009: Volume 35, Number 6

Microalbuminuria Linked to Risk of Venous Thromboembolism

Recently published data from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study indicates that microalbuminuria is independently associated with increased risk for venous thromboembolism (VTE) (JAMA 2009;301:1790–1797). Microalbuminuria is a known risk factor for arterial thromboembolic (ATE) disease, but traditionally, ATE and VTE have been viewed as different pathophysiological entities with distinct risk factors. However, recent research has implicated that ATE and VTE may be more closely related than previously thought.

In this study, the researchers found a clear and gradual relationship between 24-hour urinary albumin excretion (UAE) and the incidence of VTE in a cohort of 8,574 subjects followed for a mean of 8.6 years. The overall annual incidence of VTE was 0.14%, ranging from 0.12% in subjects with UAE <15mg/24h to 0.56% in those with UAE >300 mg/24h. In a multivariate model, UAE of 15 to 29 mg/24h, 30 to 300mg/24h, and >300 mg/24h had adjusted hazard ratios of 1.4, 2.2, and 2.82, respectively, in comparison to UAE <15mg/24h. Further analysis was confined to participants with unprovoked VTE, meaning that in the 3 months preceding VTE they had no risk factors such as major surgery, trauma, or immobilization for >7days, long-distance travel lasting >4 hours and the like. In these subjects, UAE of 15 to 29 mg/24h, 30 to 300mg/24h, and >300 mg/24h had adjusted hazard ratios of 1.07, 3.03 and 4.97, respectively, in comparison to those with UAE <15 mg/24h.

The researchers speculate that the increased risk of VTE in individuals with microalbuminuria may be related to endothelial injury and/or the related changes in levels of procoagulant proteins.

News Update
FDA Authorizes Emergency Use
of Rapid Diagnostic Swine Flu Panel

In response to requests from the CDC, the FDA has authorized certain emergency uses of the rRT-PCR Swine Flu Panel diagnostic test in connection with the recent outbreak of swine flu. The orders signed on April 27, called Emergency Use Authorization (EUA), permit the CDC to diagnose swine flu using a test that has yet to be formally approved by FDA. EUAs allow FDA, based on the evaluation of available data, to authorize unapproved or uncleared medical products or unapproved or uncleared uses of approved or cleared medical products, following a determination and declaration of emergency. The authorization ends when the declaration of emergency is terminated or the authorization is revoked by the agency.

The agency authorized the test so that qualified labs could determine if patients with flu-like symptoms have the new strain. According to FDA, the test may be effective in identifying virus subtypes that cannot be identified by other currently available tests. A positive finding will presumptively indicate that the patient has the new, previously unseen strain of H1N1 swine flu. A negative result will not be considered conclusive, by itself, that a patient does not have the virus, according to FDA. The test amplifies the viral genetic material from a nasal or nasopharyngeal swab and runs on an Applied Biosystems 7500 Fast Dx Real-Time PCR instrument or the 7500 Fast Real-Time PCR instrument.

At CLN press time, the number of H1N1 cases in the U. S. was still growing, but government officials were cautiously optimistic that the virus was not as deadly as initially thought. EUAs began under the Project Bioshield Act of 2004 involving U.S. responses to pandemics or bioterrorism. The authorizations require rapid and detailed cooperation between FDA and CDC.

Proteinuria is a Poor Predictor of Pre-eclampsia Outcomes 

A systematic review study has found that estimated levels of proteinuria is a poor predictor of both maternal and fetal complications in pregnant women with pre-eclampsia (BMC Medicine 2009;7:10). The analysis “calls into question the commonly used practice of making clinical decisions in women with pre-eclampsia based on the severity of proteinuria,” according to the authors. Proteinuria of ≥5g/24h is a widely-recognized diagnostic criterion for pre-eclampsia.

The researchers conducted an extensive literature search and selected articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. A total of 16 studies involving 6,749 subjects were included in the final analysis. Proteinuria estimation was by laboratory method only in 8 studies, by bedside dipstick urinalysis only in 5, by either of these methods in 2, and by spot urine protein:creatinine ratio in 1 study. In the included studies, summary likelihood ratios of positive and negative tests for the proteinuria threshold of 5g/24h were 1.5 and 0.73 in neonatal deaths and 1.5 and 0.78 in neonatal ICU admission. The study highlights the need for large, well-designed prospective studies to further address the utility of proteinuria levels in predicting pre-eclampsia outcomes, according to the authors.

Tight Glycemic Control Potentially Harmful in ICU Patients 

New research indicates that tight blood glucose control increased mortality in critically ill patients, in comparison to those who received conventional glucose control (N Engl J Med 2009;360:1283–97). The study calls into question the practice adopted by many hospitals of intensive control of glucose levels in critically ill patients. Previous research exploring the relationship between tight glycemic control and mortality in critically ill patients had shown mixed outcomes.

The Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial involved 6,104 intensive care unit (ICU) patients, 3,054 assigned to receive intensive glucose control and 3,050 to receive conventional control. The goal of intensive control was to maintain glucose levels between 81 and 108 mg/dL (4.5 to 6.0 mmol/L); the target in the conventional control group was ≤180mg/dL (<10 mmol/L). Patients at 42 hospitals were enrolled if they were expected to require ICU treatment for at least 3 consecutive days. Blood glucose levels were measured via point-of-care or arterial blood gas analyzers or lab analyzers.

The researchers found that the odds ratio for death with intensive glycemic control was 1.14 (95% CI, 1.02 to 1.28; P=0.02), and that the mortality difference between the two treatment groups remained significant after adjustment for pre-defined baseline risk factors. Likewise, the median survival time was lower in the intensive control group, which also experienced a statistically significantly difference in severe hypoglycemia than in the control group (6.8% versus 0.5%, respectively, with severe hypoglycemia defined as glucose levels ≤40 mg/dL (2.2 mmol/L)).

Results of the study suggest that achieving normoglycemia in critically ill patients is not necessarily beneficial and could be harmful.