The high fractional excretion (FE) of
uric acid observed in
hyponatremia associated with the syndrome of inappropriate secretion of
antidiuretic hormone (
SIADH) is commonly attributed to the volume-expanded state, although volume expansion in normonatremic volunteers is unable to increase
urate clearance to a degree similar to that in
SIADH. The goal of the present study is to analyze whether
hyponatremia by itself could influence the FE of
uric acid, as well as the effects of intravascular volume and glomerular filtration rate on FE of
uric acid in
SIADH. This study examines the effects of a 2-L infusion of isotonic saline over 24 hours on FE of
uric acid in 9 normonatremic volunteers and 17 hyponatremic patients with
SIADH. We also studied the FE of
uric acid in 6 patients with
SIADH with only mild water retention and the
urate and
creatinine clearances in 18 hyponatremic patients with
SIADH before and after normalization of serum
sodium levels by water restriction. When infusing 2 L of isotonic saline over 24 hours in healthy subjects, there was a decrease in
plasma protein concentration of 8%, suggesting a similar degree of volume expansion than in patients with
SIADH. The FE of
uric acid did not increase to the same extent (9% +/- 1.5% versus 17% +/- 1.5%; P: < 0.01). Conversely, in 6 hyponatremic patients with mild water retention (1 L), the FE of
uric acid was still high despite indirect signs of only a small increase in plasma volume. The mainstay of these observations is that chronicity of
hyponatremia by itself could affect
urate excretion. We also observed that in the patients with
SIADH, high FE of
uric acid inversely correlated with glomerular filtration rate (r = -0.66; P: < 0.01) only during the hyponatremic state. These data suggest that
hyponatremia by itself, combined with mild volume expansion and glomerular filtration rate, has a role in the high FE of
uric acid in the
SIADH.