Pathophysiology of cardiorenal syndrome in decompensated heart failure: Role of lung-right heart-kidney interaction

摘要

Cardiorenal syndrome (CRS) is defined as an interaction of cardiac disease with renal dysfunction that leads to diuretic resistance and renal function worsening, mainly with heart failure (HF) exacerbation. Hemodynamic variables linking heart and kidney are renal blood flow (cardiac output) and perfusion pressure, i.e., the aortic - renal venous pressure gradient. CRS has traditionally been interpreted as related to defective renal perfusion and arterial underfilling and, more recently, to elevation in central venous pressure transmitted back to renal veins. Our suggestion is that in a setting where aortic pressure is generally low, due to heart dysfunction and to vasodrepressive therapy, the elevated central venous pressure (CVP) contributes to lower the renal perfusion pressure below the threshold of kidney autoregulation (≤ 80 mm Hg) and causes renal perfusion to become directly pressure dependent. This condition is associated with high neurohumoral activation and preglomerular vasoconstriction that may preserve pressure, but may decrease filtration fraction and glomerular filtration rate and enhance proximal tubular sodium absorption. Thus, congestion worsens and drives the vicious cycle of further sodium retention and HF exacerbation. Lowering CVP by targeting the lung-right heart interaction that sustains elevated CVP seems to be a more rational approach rather than reducing intravascular volume. This interaction is crucial and consists of a cascade with stepwise development of pulmonary post-capillary hypertension, precapillary arteriolar hypertone, right ventricular overload and enlargement with tricuspid incompetence and interference with left ventricular filling (interdependence). The resultant CVP rise is transmitted to the renal veins, eventually drives CRS and leads to a positive feedback loop evolving towards HF refractoriness.