July 2010 Clinical Laboratory News: Diagnostic Profiles

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July 2010: Volume 36, Number 7



Chronic HCV Increases Risk for Renal Cancer

A large cohort study by researchers at Henry Ford Hospital in Detroit indicates that patients with chronic hepatitis C infection (HCV) are at increased risk for renal cell carcinoma (RCC) (Cancer Epidemiol Biomarkers Prev 2010;19:1066–73). The analysis builds on case reports during the past 5 years that suggested a link between HCV and RCC. Patients with HCV are known to be at increased risk for chronic renal disease, and the incidence of RCC has increased rapidly over the past 2 decades, but the causes behind the rise are unknown. The authors had observed RCC in their patients with HCV and sought to assess whether HCV confers risk for developing RCC.

The study involved administrative data from 67,063 adult patients treated at Henry Ford Hospital between 1997 and 2006 for whom there was a record of HCV testing. Data about RCC came from the hospital’s cancer registry. Overall, 4.6% of these individuals tested seropositive for HCV, and they were significantly more likely to be older, African American, male, and to have kidney disease than HCV-seronegative patients. As expected, HCV-seropositive patients also were at significantly higher risk for hepatocellular carcinoma than those who were seronegative.

RCC was diagnosed in 0.6% of HCV-positive patients versus 0.3% of those who were HCV-negative. The univariate hazard ratio for RCC among HCV-positive patients was 2.20; in a multivariate model that adjusted for age, race, male sex, and chronic kidney disease, the hazard ratio in HCV-positive patients was 1.77. HCV-positive patients also were significantly younger at the time of RCC diagnosis.

The researchers caution that their findings alone do not warrant a recommendation to comprehensively screen HCV-positive patients for RCC, but they suggest that clinicians should be aware of the heightened risk for RCC in this population and more carefully follow incidental renal defects detected during imaging procedures. They also call for further studies to confirm these findings and explore potential mechanisms of RCC development.

Low CHr Linked to Increased Transfusions in Critically Ill Patients 

Low reticulated hemoglobin content (CHr) on admission to an intensive care unit (ICU) was associated with higher intensity of treatment, poorer outcomes, and increased likelihood of transfusion (Anesthesiology 2010;112:1211–5). The findings could help investigators hone in on approaches to balance the risks of secondary anemia—a common problem in critically ill patients—with the potentially deleterious effects of transfusions.

Previous research indicates that critically ill patients commonly experience metabolic iron deficiency that often is caused by acute or chronic inflammation and can be exacerbated by bone marrow-stimulating agents such as erythropoietin. Two different approaches to avoid the risks of secondary anemia and potential deleterious effects of transfusions have been described in the literature—preemptive treatment with iron, folates, or erythropoietin, and models that identify which ICU patients are most likely to develop secondary anemia. The authors sought to test whether low CHr on admission was associated with ICU transfusion requirements.

At the time of ICU admission, more than one-third of patients had low CHr, defined as <29 pg. These patients were more likely to require vasoactive drugs, central venous catheter, and arterial catheter than patients with normal CHr values. In addition, patients with low CHr were more likely to have major ICU complications such as acute renal failure, ICU-acquired infection, and longer lengths of ICU stay. After adjusting for clinically significant variables such as severity of illness, age, and hemoglobin levels, the researchers found that low CHr remained significantly associated with transfusion, with a 3.6 hazard ratio.

The researchers suggest that critically ill patients with low CHr may be suitable subjects for future studies to determine whether early treatment with intravenous iron after ICU admission can reduce transfusion requirements.

Microalbuminuria Powerful Predictor of Kidney Disease in Hypertension

Italian researchers are reporting that microalbuminuria confers an almost sevenfold higher risk for chronic renal insufficiency in nondiabetic patients with hypertension (Clin J Am Soc Nephrol doi: 10.2215/CJN.07271009). The findings emphasize the usefulness of a more widespread evaluation of the urinary albumin-to-creatinine ratio (ACR) in guiding management of hypertension, according to the researchers. They also suggest that patients with microalbuminuria should be aggressively targeted for renal and cardiovascular risk factor reduction.

The Microalbuminuria: A Genoa Investigation on Complications (MAGIC) trial involved 1,122 nondiabetic patients with primary hypertension who were followed for a median of 11.8 years. The investigators conducted MAGIC to gain a better understanding of the natural history of hypertensive renal disease, especially in early stages when intervention might prevent or delay sequelae.

Urinary ACR was assessed at baseline with microalbuminuria defined as ACR ≥22 mg/g in men and ≥31 mg/g in women. A total of 10,268 person-years of follow-up revealed that baseline microalbuminuria was associated with a 7.61 relative risk (RR) of developing chronic renal insufficiency, a 2.11 RR of cardiovascular events, and a 3.21 RR of cardiorenal events. Microalbuminuria remained significantly related to chronic renal insufficiency even after adjustment for baseline covariates. The researchers also found that whereas the relationship between ACR and renal endpoint was continuous and already apparent for levels of albuminuria currently considered normal, the risk for developing a renal end point increased substantially when microalbuminuria was present.

Cycling Probe RT-PCR Fast and Accurate in Identifying Corneal Pathogens

New research indicates that real-time polymerase chain reaction (PCR) with cycling probe can simultaneously detect and quantitate bacterial and fungal pathogens in patients with corneal ulcer (Arch Ophthalmol 2010;128:535–540). The findings suggest PCR could be a fast and accurate alternative to both bacterial culture, which is time-consuming, and corneal smear examination, which depends on the lab technician’s skill.

The researchers used a cycling probe PCR assay that has a chimeric DNA-RNA-DNA probe with a strand length of 10–14 bases. RNase H cleaves the probe at the RNA linkage, enabling emission of strong fluorescence. As compared with linear or structured probes with longer-length probes, this PCR assay is highly specific with its cycling probe, according to the authors. The primers and probes used in the study were designed to simultaneously detect six pathogens, including Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa, methicillin-resistant S. Aureus, and Candida and Fusarium species.

The investigators collected two corneal scraping samples from patients who had been diagnosed with corneal ulcer and pre-treated with antibiotics before presenting at their clinic. In comparison to bacterial and fungal culture, the PCR assay had 100% sensitivity for all pathogens except Fusarium, which was not present in any of the samples, and 89.7–100% specificity. The pathogens were detected and quantified by PCR within 2 hours as opposed to culture results, which were available after 48 hours.

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