AQUARETICS AND NATRIURETICS CURRENT THERAPEUTIC USES AND FUTURE PROSPECTIVES

Abstract

SUMMARY AND CONCLUSION H yponatremia is the most common disorder of electrolytes encountered in clinical practice. Despite knowledge of hyponatremia since the mid-20th century, this common disorder remains incompletely understood in many basic areas because of its association with a plethora of underlying disease states, and its causation by multiple etiologies with differing pathophysiological mechanisms. Optimal treatment strategies have not been well defined, both due to these reasons, and because of marked differences in symptomatology and clinical outcomes based on the acuteness or chronicity of the hyponatremia. The increased urine output produced by the aquaretics (aquaretics mostly act on vasopressin receptor antagonism leading to water excretion) , is quantitatively equivalent to that of diuretics such as furosemide; qualitatively it is different in that only water excretion results and excretion of urinary solutes is not augmented. Thus, aquaretics produce solute-sparing water excretion in contrast to classic diuretic agents that block distal tubule sodium transporters, leading to simultaneous electrolyte and water losses. For this reason, the renal effects produced by this group of drugs have been termed aquaretic to distinguish them from the renal effects produced by classical diuretic agents, which are natriuretic and kaliuretic as well. This is not simply a semantic issue, because appreciating these important differences in renal effects is crucial for the intelligent clinical use of aquaretics. For example, the negative water balance induced by aquaretic agents has less adverse effect on neurohormonal activation and renal function than comparable degrees of urine output induced by loop diuretic agents, because only one third of the negative water balance induced by aquaretics derives from the ECF, whereas two thirds comes from intracellular water. Selective vasopressin 2 antagonists orally administered include (1) tolvaptan used in slowing progression in APCKD in TEMPO study and in EVEREST study for treatment of heart failure. (2) Mozavaptan present in Japan market for control of hyponatremia in paraneoplastic SIADH. (3) satavaptan showing promising results in controlling hyponatremia in liver cirrhosis patients (4) Lixivaptan involved in studies for treatment of eurovolemic hyponatremia. On the other hand conivaptan a non selective vasopressin antagonist was FDA approved for treatment of euvolemic and hypervolemic hyponatremia in hospitalized patients. Despite the fast growth of aquaretic medical uses, and apart from expensive price of such medications, limitations arise. Including polyurea, dehydration & potential comorbidities related to it , limited use to early stages of APCKD even FDA warning about tolvaptan usage over 30 days for fear of severe liver damage, and attributing its solwering of