[Diuretic therapy in congestive heart failure--new views on spironolactone therapy]

Cardiac pump failure leads to a reduction of the effective arterial volume. This is sensed by the kidney via afferent sympathetic fibres. The renal response to the perceived lack of volume is the retention of sodium and water. Although initially homeostatic, this renal counterregulation is maladaptive later on and may contribute to further cardiac compromise by increasing preload (volume retention) and afterload (hyperreninism). The renal sodium retention in congestive heart failure is a consequence of the activation of the sympathetic nervous system and of the renin-angiotensin-aldosterone system. The retention of osmotically free water is partly caused by the nonosmotic secretion of antidiuretic hormone from the posterior pituitary and partly by a diminished osmoregulatory capacity of the kidney due to diuretic therapy and/or (pre-)renal insufficiency. In the near future specific blocking drugs of vasopressin receptors should become available which could make a significant contribution to the management of hyponatremia in this setting. For the management of extracellular volume overload a negative sodium balance is the central objective. A moderate reduction of sodium intake is helpful to achieve this goal and has the additional benefit of reducing thirst and renal potassium loss. However, the majority of patients require (loop) diuretics in addition. Patients who are refractory to high and repeated doses of loop diuretics may respond to a combination of diuretics which act on different nephron segments. Diuretics increase the risk of hypokalemia which can trigger life-threatening tachyarrhythmia, particularly in patients with cardiac dysfunction. Hypokalemia is therefore an indicator of an adverse outcome. Secondary hyperaldosteronism--which can persist despite effective therapy with ACE-inhibitors--is the major cause of hypokalemia in this setting. The randomized aldactone evaluation study (RALES) has shown that spironolactone (25 mg/day) reduced the risk of hypokalemia and decreased morbidity, mortality and clinical symptoms in patients with heart failure. The recent encouraging results with vasopressin receptor antagonists and spironolactone point to the fact that the therapeutic modification of maladaptive homeostatic renal mechanisms plays an increasingly important role in the modern diuretic management of heart failure beyond symptomatic relief from volume overload.