Large A-V fistula: pathophysiological consequences and therapeutic perspectives

Large Arteriovenous Fistulae (AVF) can increase cardiac output. This may result in the development of congestive heart failure, a clinical situation associated with increased activity of Vasoconstrictor neurohormonal systems: the Renin-angiotensin system (RAS), Sympathetic nervous system (SNS), the Endothelin system and Arginine vasopressin (AVP). At the same time there is compensatory activation of systemic and vasodilating systems: Atrial natriuretic peptide (ANP) and Nitric oxide (NO). Previous data from our laboratory and other groups suggest that urinary sodium excretion in this situation is largely determined by the balance between two antagonistic hormonal systems: the vasoconstrictor/sodium-retaining factors such as RAS, endothelin, and SNS, and vasodilatory/natriuretic substances such as ANP and NO. In decompensated patients, enhanced activities of the sodium-retaining systems overwhelm the effects of vasodilatory/natriuretic systems, which lead to a net reduction in sodium and water excretion. For compensation to occur, the effects of natriuretic mechanisms must prevail over those of the opposing systems, resulting in renal sodium/water excretion. This notion is supported by clinical and experimental studies where pharmacological intervention corrected the imbalance present in AVF. Thus, a shift in the balance in favor of natriuresis may be achieved either by increasing the activity of natriuretic factors or reducing the influence of the antinatriuretic systems. Based on that, the use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II (ATII) blockers may be beneficial in the management of patients with large AVF.