Involvement of Arginine Vasopressin and Renal Sodium Handling in Pathogenesis of Hyponatremia in Elderly Patients.

Abstract

Abstract. The present study was undertaken to determine the pathophysiological role of arginine vasopressin (AVP) in elderly patients with hyponatremia, and the efficacy of fludrocortisone acetate in treating their hyponatremia. Eleven hospitalized patients aged 65 years or older whose serum sodium levels were less than 130 mEq/l were examined. The hyponatremic patients included two groups of patients: syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and central salt-wasting syndrome. And 24 healthy, young subjects aged 20 to 34 years, and 24 healthy, elderly subjects aged 65 to 80 years were recruited by community announcement. The elderly subjects had decreased urinary concentrating ability and exaggerated response of AVP secretion to osmotic and nonosmotic stimuli, as compared to the young subjects. All the patients had hyponatremia, with the exaggerated urinary loss of Na. Plasma AVP levels were elevated despite hypoosmolality in all the 2 groups of hyponatremic, elderly patients. Plasma renin activity and plasma aldosterone concentrations were low in the patients with SIADH and central salt-wasting syndrome. Fludrocortisone acetate therapy was effective in the patients with central salt-wasting syndrome and 3 patients with SIADH whose hyponatremia remained unchanged after water restriction. Water restriction therapy normalized serum Na levels in only 3 patients with SIADH. These results indicate that AVP is involved in the mechanism for hyponatremia in the elderly patients with SIADH and central salt-wasting syndrome. Severe hyponatremia associated with SIADH and central salt-wasting syndrome responds well to mineralocorticoid therapy. Both the secretion of AVP and renal sodium handling may be involved in the mechanisms of action of the disorders. The diagnostic criteria for SIADH in the elderly patients may have to be reevaluated and should be considered to indicate fludrocortisone acetate therapy.

Interaction of Osmotic and Nonosmotic Stimuli in Regulation of Vasopressin Secretion in Hypoosmolar State of Man.

“…This may be due to a lack of sensitive and specific means in identifying the extracellular fluid volume status. Of several parameters of fluid homeostasis, high PRA and low urinary sodium concentrations may be the most useful predictors for the presence of hypovolemic hyponatremia [26], but PRA may not be increased in elderly patients such as those included in he present study [12,14,15,18]. Urinary sodium excretion may be high in hypovolemic hyponatremia due to salt wastage by the kidneys.…”

“…In addition, these patients had weight loss as well as an increase in PRA in one of them, and sodium supplement or mineralocorticoid therapy after the saline infusion study eventually corrected the clinical state and hyponatremia in these patients. These findings, therefore raise the possibility of an underlying hypovolemic stimulus [12,18], even though SIADH could be present. These patients had hypoproteinemia.…”

“…Their normal to low PRA, plasma urate and creatinine as well as their increased urinary sodium excretion are suggestive of normal or increased total body water due to a primary abnormality in the inhibitory control of AVP secretion (i.e., the syndrome of inappropriate antidiuretic hormone secretion; SIADH). Nevertheless, there are no definitive proofs of euvolemia or hypervolemia since these laboratory data could result from other factors such as normal aging [14,151, hyporeninimic hypoaldosteronism (patient 5) and hypovolemic hyponatremia in patients with miscellaneous diseases [12,[16][17][18]. In addition, these patients had weight loss as well as an increase in PRA in one of them, and sodium supplement or mineralocorticoid therapy after the saline infusion study eventually corrected the clinical state and hyponatremia in these patients.…”

“…Urinary sodium excretion may be high in hypovolemic hyponatremia due to salt wastage by the kidneys. A careful evaluation is necessary to determine the cause of hyponatremic disorders in elderly subjects [12,18].…”

Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency

“…Therefore, the derangement in adrenocortical hormones had little effect on enhanced urinary Na excretion (23,24). Rather, renal Na handling per se is attenuated in the elderly subjects (15), and this factor could be associated with the elevation of urinary Na excretion in the elderly group with secondary adrenal insufficiency.…”