However, conventional strategies are often limited by poor patient tolerance (e.g., difficulty adhering to strict fluid restriction), slow onset of effect, and high failure rates-particularly when urine osmolality remains high or the inciting stimulus for ADH secretion persists-resulting in a substantial proportion of patients with refractory hyponatremia who require stepwise, evidence-based escalation of therapy [5,9,20]. The gene discussed is AVP; the disease is Hyponatremia.