July 2009 Clinical Laboratory News: Diagnostics Profiles

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July 2009: Volume 35, Number 7

A New, More Accurate eGFR Equation

Investigators in the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), a research group established by the National Institute of Diabetes and Digestive and Kidney Diseases, have developed a new equation for estimated glomerular filtration rate (eGFR) (Ann Intern Med 2009;150:604–612). The new equation is more accurate than previous estimates and could replace the commonly used Modification of Diet in Renal Disease (MDRD) Study equation for estimating GFR in routine clinical practice, according to the researchers.

Most clinical labs use the MDRD Study equation to report eGFR when serum creatinine is ordered. This equation uses serum creatinine level, age, race, sex, and body size for eGFR, which is considered the best overall index of kidney function. However, since the MDRD Study equation was developed by studying patients with chronic renal disease it is imprecise and has a bias in underestimating GFR at higher values. So the researchers’ goal was to develop and validate a new estimate equation based on serum creatinine levels that would be as accurate as the MDRD Study equation at a GFR <60mL/min per 1.73 m2 and more accurate at a higher GFR.

The researchers pooled data from 10 studies involving 8,254 participants into separate data sets for development (5,504 subjects) and internal validation of the equation (2,750 subjects). Another 16 studies involving 3,896 subjects were used to perform the external validation. A succession of statistical models were used to validate the development, internal validation and external validation data sets, as well as to develop the equation and metrics for assessing the performance of the equation.

The researchers found that the new CKD-EPI equation was as accurate as the MDRD Study equation in the subgroup of validation data set subjects with eGFR <60 mL/min per 1.73 m2 and substantially more accurate in the subgroup with eGFR >60 mL/min per 1.73 m2. In comparing the two data sets using NHANES data, the researchers found that the CKD-EPI equation yielded a lower estimated prevalence of chronic kidney disease than the MDRD Study equation, primarily because of a lower estimated prevalence of stage 3 disease. The new equation should lead to more accurate estimation of the burden of chronic kidney disease and improved clinical decision making, primarily by reducing the rate of false-positive diagnoses. A limitation of the study is its non-representative sampling of the general population with limited representation of subjects older than age 70 and racial and ethnic minorities. In addition, the CKD-EPI equation is more complex than the MDRD Study equation.

Routine Occult Bacteremia Culture May No Longer Be Warranted

A recent retrospective cohort study suggests that the rate of occult bacteremia (OB) in young children is low enough that consideration should be given to no longer routinely obtaining blood cultures in most of these patients (Acad Emerg Med 2009; 16:220–225). The impetus for the study was that after introduction of the pneumococcal conjugate vaccine (PCV) and despite published guidelines and studies documenting PCV immunization rates, OB blood culture continues to be a routine practice in pediatric ambulatory care. Guidelines have recommended eliminating the work-up for OB once an effective PCV is widely in use, and experts had suggested that once disease prevalence was <1% OB culture would no longer be necessary. The authors speculated that one reason OB blood culture continues to be the norm may be a reflection of concerns about the sample sizes and designs of previous studies that have examined OB prevalence after the introduction of PCV.

In the new study, researchers from Phoenix Children’s Hospital studied the prevalence of OB in 8,408 well-appearing, previously healthy children age 3 to 36 months who presented at the emergency department with a temperature ≥39ºC and no recognized source of the fever on physical exam. They found that there were 21 true-positive OB cases, yielding a rate of 0.25% (95% CI = 0.16% to 0.37%), and 159 contaminant cultures, yielding a contaminant rate of 1.89% (95% CI = 1.61% to 2.19%). Streptococcus pneumoniae grew in 14 cultures, for a rate of 0.17% (95% CI = 0.09% to 0.27%). The researchers calculated that 588 children would need to be tested to detect one case of S. pneumoniae. Using previously published estimates of the progression of S. pneumoniae without antibiotic treatment to meningitis, neurological complications and death, the authors calculated that they would need to test 14,700 children to detect one case of S. pneumoniae meningitis, 49,000 children to prevent one neurologic sequelum, and 184,000 children to prevent one death from S. pneumoniae meningitis.

The authors concluded that it is time to reconsider existing treatment protocols in this cohort of young children who present with fever without source. “The rate of OB is sufficiently low to preclude laboratory testing in favor of close follow-up,” they observed.

Study Suggests New Parathyroid Hormone-related Peptide Testing Strategy

New research has confirmed the limited value of parathyroid hormone-related peptide (PTHrP) testing in the assessment of hypercalcemia and established a cutoff below which PTHrP testing appears to be unnecessary in the work-up of hypercalcemia (Clinica Chimica Acta 2009;402:146–149). The findings could help reduce inappropriate PTHrP testing and guide the clinical work-up of hypercalcemia.

The researchers sought to find a better test ordering strategy using calcium, parathyroid hormone, and PTHrP for the assessment of hypercalcemia because in their experience, evaluations of total calcium often prompt simultaneous requests for PTH and PTHrP tests, “an inappropriate strategy that wastes laboratory resources,” according to the authors. They also had observed that PTHrP is sometimes even requested in hypocalcemic patients.

The retrospective study involved test results from 123 patients who had total calcium and PTH tests performed within 2 days of a PTHrP test. Hypercalcemia was defined as a total calcium concentration >2.55 mmol/L (>10.2 mg/dL). Of all the subjects, 47 were identified as having hypercalcemia of malignancy, but only 15 of those had PTHrP concentrations above the reference interval, confirming the low sensitivity of PTHrP for identifying the condition, which has been described in prior research. A PTH concentration range of 1.0 to 26 ng/L, with a mean of 10 ng/L was observed in patients who had both hypercalcemia and increased PTHrP. Based on these findings the authors concluded that PTHrP testing is unnecessary in hypercalcemic patients with a PTH >26ng/L.

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