B-Natriuretic Peptide (BNP) Testing

By Thomas Reppun, MD, DLS Associate Medical Director, November 8, 2002

The DLS-QMC Laboratory will be providing BNP testing on a routine and STAT basis in late November, 2002 using the BioSite® Diagnostics Triage® system.

B-Natriuretic Peptide (BNP) is a 17 ring structured amino acid which acts to regulate blood pressure and fluid balance. BNP was first isolated from porcine brain tissue. Subsequent studies have shown that the ventricles of the heart are the primary source. BNP release occurs as a result of ventricular distension and pressure overload. BNP produces natriuresis, diuresis, and vasodilatation by binding to the transmembrane guanylate cyclase receptor which results in conversion of guanosine triphosphate to cGMP. BNP is cleared from circulation via NPR-C (natriuretic peptide receptor) in the blood and is degraded by a neutral peptidase which cleaves the ring structure.

The precursor form of BNP is Pro-BNP. This distinction is important because naturally produced BNP and the new drug Nesiritide (Natrecor®) are identical; the BNP assay will not distinguish between the two. New assays for (N)Pro-BNP are expected in the near future and will distinguish Pro-BNP from exogenous and endogenous BNP.

Elevations in BNP are seen in the following conditions: CHF, LV hypertrophy, diastolic and/or systolic ventricular dysfunction, ischemic heart disease, cor pulmonale resulting from pulmonary hypertension and pulmonary embolus, and fluid overload associated with cirrhosis and chronic renal failure.

BNP levels roughly correlate with the degree of congestive heart failure as defined by the NYHA functional classification. From the following table, it is evident that there is considerable overlap between the different functional classes:

BNP testing at DLS will be performed using the BioSite® Diagnostics Triage® system and reagents. The test is a fluorescence immunoassay performed on EDTA (purple top) anticoagulated whole blood or plasma. EDTA plasma results are approximately 7% less than whole blood results. The sample may be held at room temperature for up to four (4) hours and thereafter the plasma must be stored frozen at -20 C. The reagents include a pair of murine monoclonal and polyclonal antibodies. Testing time is approximately 20 minutes. STAT turnaround time for results upon receipt of the specimen in the laboratory will be approximately 30 minutes.

The linearity of the assay is from 5 - 1300 pg/ml. To date there are no reported drug interferences with the assay. Although hemolyzed specimens should be avoided, there is no significant effect from hemolysis or lipemia. The assay has a CV ranging from 10 - 15%.

The upper limit of normal for patients without heart or renal disease is probably less than 60 pg/ml (see table below and attached annotated reference list).

The normal range for BNP will be set at 100 pg/ml and is based upon the manufacturer's studies where 95% of patients >55 years old without CHF have values < 100 pg/ml. Although the mean BNP increases with age, the increase is probably the result of increasing rates of underlying heart disease. The results for women tend to run higher than men.