Abstract
N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r2 = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox’s proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic parameters and outcome regardless of renal function. By using higher cut-off values, NT-proBNP seems to represent a valid clinical marker even in PH patients with renal insufficiency.
Highlights
Pulmonary hypertension (PH) is characterized by elevated pulmonary vascular resistance (PVR) leading to right ventricular overload, hypertrophy and dilation, and eventually causing right ventricular failure and death [1]
PAH-specific therapy at time of right heart catheterization according to group of disease, i.e. PAH or CTEPH, are given in table S1
According to our data in pre-capillary PH patients, NT-proBNP levels are significantly affected by the renal function and accumulate in the presence of renal impairment
Summary
Pulmonary hypertension (PH) is characterized by elevated pulmonary vascular resistance (PVR) leading to right ventricular overload, hypertrophy and dilation, and eventually causing right ventricular failure and death [1]. Brain natriuretic peptide (BNP) and the N-terminal fragments of its pro-hormone, N-terminal pro-brain natriuretic peptide (NTproBNP), have been implicated as functional biomarkers in a variety of cardiovascular diseases [6]. Levels of BNP and NTproBNP are elevated following ventricular impairment and reflect the severity of hemodynamic dysfunction in heart disease [6]. BNP and NT-proBNP are released from ventricular myocytes in response to mechanical stretching, e.g. due to increased chamber pressure or volume overload [7,8]. Besides an increased release, elevated NT-proBNP levels may result from altered metabolism and/or decreased elimination from the circulation. It has been shown that impaired renal function with a decreased glomerular filtration rate (GFR) leads to accumulation of NTproBNP and might hamper its prognostic utility [10,11]
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