Relationship between kidney function, hemodynamic variables and circulating big endothelin levels in patients with severe refractory heart failure

Abstract

Fluid retention is a major characteristic of symptomatic, progressive heart failure when a main factor implicated in the pathogenesis of renal dysfunction is renal hypoperfusion. This may be a consequence of forward cardiac failure, resulting in a low cardiac output integrating poor left ventricular function secondary to myocardial impairment and increased resistance in the regional renal vasculature secondary to locally released vasoconstrictors, e.g. endothelin. So far, the role of the pulmonary circulation in perpetuating renal dysfunction in heart failure is unclear.

Methods: We investigated the relationship of hemodynamic variables obtained during right heart catheterization and plasma big endothelin levels to renal function variables in 18 male patients aged 52 +/- 3 years, with heart failure in the NYHA function class III-IV, based on idiopathic causes in 8 and ischemic causes in 10 patients. Renal plasma flow (RPF) was established by paraaminohippurate (PAH) clearance and the glomerular filtration rate (GFR) was measured by iothalamate clearance.

Results: Plasma big endothelin (ET) levels were increased above the upper normal range (1.8 fmol/ml) in 16 out of 18 patients, averaging 5.0 +/- 0.8 fmol/ml (1.7-11.9 fmol/ml). Positive correlations to big ET plasma levels were detected with mean pulmonary pressure (r = 0.73, p < 0.001) pulmonary capillary wedge pressure (r = 0.56, p < 0.05) and pulmonary vascular resistance index (r = 0.69, p < 0.01). Glomerular filtration rate (70 +/- 7 ml/min) and renal plasma flow (358 +/- 36 ml/min) were considerably reduced and exhibited a tendency to correlate inversely with big ET levels (r = -0.46, p = 0.056 and r = -0.44, p = 0.069, respectively). Contrary to expectations, RPF did not correlate significantly with cardiac index, systemic vascular resistance index or arterial blood pressure. In contrast, significant correlations were detected of RPF with pulmonary capillary wedge pressure (r = -0.69, p < 0.01), mean pulmonary artery pressure (r = -0.65, p < 0.01), right atrial pressure (r = -0.47, p < 0.05) and right ventricular ejection fraction (r = 0.49, p < 0.05).

Conclusion: The findings suggest a role for endothelin in renal vasoconstriction and accord well with the concept that in severe heart failure renal hypoperfusion--by volume retention--as well as increased endothelin synthesis--by pulmonary vasoconstriction--play a part in the increased pulmonary filling pressures.