Evidence that chronicity of hyponatremia contributes to the high urate clearance observed in the syndrome of inappropriate antidiuretic hormone secretion

The high fractional excretion (FE) of uric acid observed in hyponatremia as sociated with the syndrome of inappropriate secretion of antidiuretic hormo ne (SIADH) is commonly attributed to the volume-expanded state, although vo lume expansion in normonatremic volunteers is unable to increase urate clea rance to a degree similar to that in SIADH. The goal of the present study i s to analyze whether hyponatremia by itself could influence the FE of uric acid, as well as the effects of intravascular volume and glomerular filtrat ion 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 normo natremic volunteers and 17 hyponatremic patients with SIADH. We also studie d the FE of uric acid in 6 patients with SIADH with only mild water retenti on and the urate and creatinine clearances in 18 hyponatremic patients with SIADH before and after normalization of serum sodium levels by water restr iction. When infusing 2 L of isotonic saline over 24 hours in healthy subje cts, there was a decrease in plasma protein concentration of 8%, suggesting a similar degree of volume expansion than in patients with SIADH. The FE o f 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 re tention (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 inv ersely correlated with glomerular filtration rate (r = -0.66; P < 0.01) onl y during the hyponatremic state. These data suggest that hyponatremia by it self, combined with mild volume expansion and glomerular filtration rate, h as a role in the high FE of uric acid in the SIADH. (C) 2000 by the Nationa l Kidney Foundation, Inc.