Q and A

September 2006

Richard A. Savage

Q: B-type natriuretic peptide and N-terminal-proBNP are cleared by the kidney, and patients with renal disease generally have higher serum BNP and NT-proBNP values than matched patients without renal disease. How should we inform the requesting physician that the BNP/NT-proBNP results may not accurately reflect left ventricular stretching/dysfunction in patients with renal disease?

A. Impaired renal function increases the risk of cardiovascular mortality, all-cause mortality, and morbidity in congestive heart failure, or CHF, patients, with an estimated glomerular filtration rate, or eGFR, of less than 60 mL/min. independently associated with adverse events. Blood-plasma concentrations of BNP and NT-proBNP are objective biomarkers for diagnosing CHF caused by systolic and diagnostic dysfunction. The majority of patients with chronic kidney disease develop cardiovascular complications, so it is necessary to differentiate elevated BNP/NT-proBNP values due to left ventricular dysfunction and CHF from elevated BNP/NT-proBNP values due to possible decreased clearance as a result of kidney disease. Smaller studies of pre-dialysis chronic kidney disease patients appear to favor BNP over NT-proBNP as the marker of choice to test for CHF. But the larger body of recent clinical evidence demonstrates that both assays are acceptable if used appropriately, as noted in our discussion here.^1–5

Plasma BNP and NT-proBNP concentrations are independently affected by eGFR and left ventricular mass index. Vickery et al demonstrated that mean BNP concentration increased by 20.6 percent per 10 mL/min./1.73 m² reduction in eGFR, while mean NT-proBNP concentrations increased 37.7 percent.¹ Tsutamoto et al also showed that decreased renal clearance contributed to increased BNP in CHF patients with renal dysfunction, especially in patients with eGRF of less than 60 mL/ min.A recent study by Richards et al of stable ischemic heart disease patients demonstrated that BNP and NT-proBNP developed strong and similar test performance in ruling out severely reduced left ventricular ejection fraction and in predicting all-cause mortality in CHF despite renal function.³ Finally, results from the ProBNP Investigation of Dyspnea in the Emergency Department, or PRIDE, study demonstrated that the use of NT-proBNP was valuable for assessing dyspenic patients with suspected CHF, irrespective of renal function.^4,5

While the relationship between renal function and BNP or NT-proBNP differ, using appropriate evidence-based cutoff concentrations allow for the use of either BNP or NT-proBNP in assessing patients with renal insufficiency.

References:

1. Vickery S, Price CP, John RI, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CDK: relationship to renal function and left ventricular hypertrophy. Am J Kid Dis. 2005; 46: 610–620.

2. Tsutamoto T, Wada A, Sakai H, et al. Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure. J Am Coll Cardiol. 2006;47:582–586.

3. Richards M, Nicholls MG, Espiner EA, et al. Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease. J Am Coll Cardiol. 2006;47: 52–60.

4. Anwaruddin S, Lloyd-Jones DM, Baggish A, et al. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. J Am Coll Cardiol. 2006; 47: 91–97.

5. Schou M, Dalsgaard MK, Clemmesen O, et al. Kidneys extract BNP and NT-proBNP in healthy young men. J Appl Physiol. 2005;99:1676–1680.

Fred S. Apple, PhD
Medical Director, Clinical Laboratories
Hennepin County Medical Center
Professor, Laboratory
Medicine and Pathology
University of Minnesota
School of Medicine
Minneapolis

Kristin A. Johnson, MD
Resident Physician
Laboratory Medicine and Pathology
University of Minnesota
School of Medicine
Minneapolis

Q: Who should monitor the point-of-care testing performed in an ambulance?

A. Any laboratory that performs testing on human specimens to obtain information that can be used for the diagnosis, prevention, or treatment of disease is subject to CLIA regulations. This includes mobile labs, ambulances, direct access testing, health screening fairs, and other temporary testing locations. All facilities that meet the definition of “laboratory” under CLIA must obtain an appropriate CLIA certificate before conducting patient testing.

The Centers for Medicare and Medicaid Services ordinarily requires that each location have a separate CLIA certificate, but a parent location may hold the CLIA certificate for mobile testing units. According to the CLIA ’88 final rule, Federal Register (2003) [42 CFR 493.35 and 42 CFR 493.43], this exception applies to temporary testing locations that perform waived or provider-performed microscopy procedures, such as mobile units providing laboratory testing or health screening fairs. Not-for-profit or federal, state, or local government laboratories that engage in limited (not more than a combination of 15 moderately complex or waived tests per certificate) public health testing may also file a single application. Oversight of testing performed on the mobile units would be the responsibility of the person listed as laboratory director on the CLIA certificate. The requirements for CAP accreditation would be the same as for any clinical laboratory.

Joan Rose
Technical Specialist
Laboratory Accreditation Program
College of American Pathologists
Northfield, Ill.

Q: Should we perform a microscopic urine exam on a negative dipstick?

A. This is a question that has been asked, and answered, many times over the past few decades, especially since the advent of automated urinalysis machines and more sophisticated and accurate dipsticks. The answer is sometimes—it depends on numerous factors, including the type of survey population, state of the patient’s health, age, prior medical conditions, drugs, and diet. Many laboratories have all but eliminated the urine microscopic examination when the dipstick is negative, especially in a normal adult population since the percent return is very low, usually less than two percent. The modern multi-pad dipstick is a very good screening tool, but it’s not infallible—it is not a quantitative means of testing. On the other hand, in a hospital patient population, the percent of dipstick-positive results is much higher—about 10 percent or more. Therefore, a more exact, such as a microscopic, examination of the urine is often warranted. Some rare diseases produce substances in the urine that are not detectable by dipstick methodology. Finally, interfering substances can mask dipstick reactions, leading to false-negative or false-positive results.

Meryl H. Haber, MD
Scottsdale, Ariz.