Atrial Natriuretic Factor, Renal Failure and Hemodialysis

Atrial natriuretic factor (ANF), a biologically active peptide produced mainly in cardiomyocytes, is released into the circulation in response to atrial distension secondary to an increase in central blood volume and/or atrial pressure (1-2). In vivo and in vitro studies have shown that ANF can relax vascular smooth muscle, enhance excretion of sodium and water, inhibit the renin aldosterone system and antagonise the vasoconstrictor actions of angiotensin II and norepinephrine (3-5). This spectrum of activity has lead to suggestions that ANF may be an important element in the homeostatic regulation of extracellular fluid volume and blood pressure (6-7). In exploring regulatory mechanisms and responses of the ANF system in disease states associated with abnormal control of extracellular body fluids, renal failure has become an interesting area of focus. Patients with end-stage renal disease on chronic dialysis cannot maintain body fluid balance and extracellular fluid volume varies cyclically, gradually increasing during the interdialysis interval and decreasing rapidly during hemodialysis, often in association with impaired blood pressure control. Suggestions that release of ANF under these circumstances may represent a cardiac response to changes in preload and afterload, has lead to speculation on the existence of a link between plasma ANF levels and blood pressure in hypervolemia-prone uremic patients and to controversy concerning the potential physiological or pathological significance of the ANF system under these conditions. Seen in this context, ANF has been considered by some as a uremic toxin contributing to hypotension and hemodynamic instability following dialysis (8), yet viewed by others as a potentially beneficial agent limiting production or activity of several compounds which may otherwise exacerbate sodium retention and hasten the development of hypertension (9-13). In an attempt to resolve these differing opinions approximately nineteen papers, primarily concerned with the investigation of plasma irANF levels before and after dialysis in end-stage renal patients, have appeared over the last three years (8-27). A brief summary of these data is presented in Table I. The main aims of these studies have been to establish how and to what extent circulating irANF levels are altered during end stage renal disease and hemodialysis and to clarify whether such changes primarily reflect an appropriate response by the heart to variations in intravascular fluid load or whether other mechanisms are also involved. As shown in Table I there is consensus among all investigators that plasma irANF levels are increased prior to, and decrease to a greater or lesser extent following, either hemodialysis or ultrafiltration. In 45% of the studies, hemodialysis restored irANF levels to essentially normal values (9-13, 18-20, 23). These data clearly implicated fluid overload as the major factor responsible for elevated predialysis levels and suggested the potential usefulness of plasma irANP measurements as an index of volume expansion (10, 18). In contrasting reports, however, an inability to detect correlations with changes in weight or hematocrit (16, 26) and, in particular, the occurrence of residually high plasma levels of irANF after dialysis compared to what were considered normal values (8, 15, 16, 26), prompted suggestions that factors other than simple volume expansion may determine pre and post dialysis plasma irANF levels and questioned the physiological significance and diagnostic value of changes in irANP under these conditions. Since ANF has vasorelaxant properties it was suggested that elevated levels found in some patients after dialysis could in theory have a detrimental effect on hemodynamic stability (8). Furthermore, reductions in the rate of degradation and renal clearance have been proposed as additional plausible mechanisms which could ostensibly influence levels of irANF pre and post dialysis (27). At first sight, these suggestions may appear to necessitate a re-evaluation of initial ideas concerning underlying mechanisms, role and significance of changes in plasma irANF in end-stage renal disease;