From the Guidelines
Pro-BNP levels are significantly affected by renal clearance, and patients with severe renal dysfunction (glomerular filtration rate <30 mL/min/1.73 m2) will have increased NT-proBNP/BNP ratios due to impaired clearance mechanisms. The biological half-life of BNP ranges from 13 to 20 min and that of NT-proBNP from 25 to 70 min 1. B-type natriuretic peptide is cleared via clearance receptors and to a lesser extent by degradation by neutral endopeptidase, while NT-proBNP is cleared passively by organs with high blood flow, such as the kidneys, liver, and muscles 1. Key points to consider include:
- The proportion of calculated total body NT-proBNP clearance is 55–65% by the kidneys, 20 –25% across the liver, 10–15% across the musculoskeletal tissue, and 5–10% across the head and neck 1
- N-terminal proB-type natriuretic peptide renal extraction is maintained in the presence of moderate kidney dysfunction, but in case of severe renal dysfunction, NT-proBNP/BNP ratios increase for unclear reasons 1
- Patients with reduced kidney function will typically have elevated Pro-BNP levels even in the absence of heart failure, as the peptide accumulates when it cannot be properly cleared by the kidneys 1. When evaluating patients with kidney disease, it's advisable to consider the trend of Pro-BNP values over time rather than absolute values, and to correlate findings with clinical symptoms and other diagnostic tests such as echocardiography.
From the Research
Pro BNP and Clearance
- Pro BNP levels are affected by clearance, particularly renal clearance 2, 3
- Studies have shown that renal dysfunction can increase plasma concentrations of Pro BNP, with a significant correlation between glomerular filtration rate (GFR) and Pro BNP levels 2
- The effect of renal dysfunction on Pro BNP levels is similar to that of BNP, with both markers being elevated in patients with renal dysfunction 2
- The ratio of NT-proBNP to BNP is influenced by renal function, with a higher ratio observed in patients with decreased renal function 3
Factors Influencing Pro BNP Levels
- Renal function: decreased GFR is associated with increased Pro BNP levels 2, 3
- Age: increasing age is associated with a higher ratio of NT-proBNP to BNP 3
- Body mass index (BMI): BMI is inversely correlated with the ratio of NT-proBNP to BNP 3
- Atrial fibrillation: the presence of atrial fibrillation is associated with a higher ratio of NT-proBNP to BNP 3
Clinical Implications
- Pro BNP levels should be interpreted in the context of renal function, with consideration of the potential for elevated levels in patients with renal dysfunction 2, 3
- The use of Pro BNP as a diagnostic and prognostic marker in heart failure should take into account the potential influence of renal function on its levels 4, 5
- Further research is needed to establish appropriate thresholds for Pro BNP levels in patients with and without heart failure, particularly in the context of renal dysfunction 4, 5