Decaux G, Namias B, Gulbis B, Soupart A
Unité de Recherche du Métabolisme Hydrominéral, Hôpital Universitaire Erasme, Université Libre de Bruxelles, Belgium.
J Am Soc Nephrol. 1996 May;7(5):805-10. doi: 10.1681/ASN.V75805.
In hyponatremia related to syndrome of inappropriate antidiuretic hormone (SIADH), hypouricemia is explained primarily by the high uric acid clearance rate that results from the decrease in tubular uric acid reabsorption. This modification of tubular handling of uric acid is considered to be induced by the increase in the "effective vascular volume". This study was designed to determine if V1-receptor stimulation participates in the development of a high uric acid clearance rate as in SIADH, in which the antidiuretic hormone acts on V1 and V2 receptors. Therefore, the urate clearance rate was measured in seven volunteers with 1-desamino-8-D-arginine vasopressin (dDAVP)-induced hyponatremia, with dDVAP stimulating exclusively the V2 receptors (Group I), and in six patients with SIADH (Group II) during both normo- and hyponatremia. As expected, in both groups, the serum uric acid concentration decreased during hyponatremia, but did so to a larger extent in the patients with SIADH (-53% versus -29%, P < 0.02). Despite similar levels of hyponatremia (126 +/- 5 mmol/L and 125 +/- 5.5 mmol/L), of hypoproteinemia (64 +/- 5 g/L and 63 +/- 5 g/L) and of salt excretion (FENa, 0.66 +/- 0.28% and 0.73 +/- 0.25%), the urate clearance (8.3 +/- 3.3 mL/min) and the fractional excretion of filtered uric acid (5.7 +/- 2%) in Group I were not significantly different during hyponatremia than during normonatremia (6.4 +/- 1.5 mL/min and 5.4 +/- 0.9%). On the other hand, in Group II, both parameters were increased (17.8 +/- 2.9 mL/min and 19.6 +/- 5.3%; P < 0.001) and both values were higher than in the dDAVP-induced hyponatremia (P < 0.01). Additionally, the administration of a potent V1-receptor agonist (triglycyl-lysine-vasopressin) in a patient with central diabetes insipidus with preexisting dDAVP-induced hyponatremia produced a rapid increase of urate clearance. Because dDAVP acts only on the V2 receptors, these data suggest that the higher urate clearance observed during hyponatremia related to SIADH is not only the consequence of an increased "effective vascular volume," but that V1-receptor stimulation also contributes to it, by a mechanism that remains to be determined.
在与抗利尿激素分泌失调综合征（SIADH）相关的低钠血症中，低尿酸血症主要是由于肾小管尿酸重吸收减少导致尿酸清除率升高所致。肾小管对尿酸处理的这种改变被认为是由“有效血容量”增加所诱导的。本研究旨在确定V1受体刺激是否像在SIADH中一样参与高尿酸清除率的发生发展，在SIADH中抗利尿激素作用于V1和V2受体。因此，对7名因1-去氨基-8-D-精氨酸血管加压素（dDAVP）诱导低钠血症的志愿者（仅刺激V2受体，I组）以及6名SIADH患者（II组）在血钠正常和低钠血症期间测量尿酸清除率。正如预期的那样，两组在低钠血症期间血清尿酸浓度均降低，但SIADH患者降低幅度更大（-53%对-29%，P<0.02）。尽管两组低钠血症水平相似（分别为126±5 mmol/L和125±5.5 mmol/L）、低蛋白血症水平相似（分别为64±5 g/L和63±5 g/L）以及盐排泄情况相似（滤过钠排泄分数，分别为0.66±0.28%和0.73±0.25%），但I组在低钠血症期间的尿酸清除率（8.3±3.3 mL/min）和滤过尿酸分数排泄率（5.7±2%）与血钠正常期间（6.4±1.5 mL/min和5.4±0.9%）相比无显著差异。另一方面，II组这两个参数均升高（分别为17.8±2.9 mL/min和19.6±5.3%；P<0.001），且均高于dDAVP诱导的低钠血症（P<0.01）。此外，在一名患有中枢性尿崩症且已有dDAVP诱导低钠血症的患者中给予强效V1受体激动剂（三甘氨酰赖氨酸血管加压素）后，尿酸清除率迅速升高。由于dDAVP仅作用于V2受体，这些数据表明，与SIADH相关的低钠血症期间观察到的较高尿酸清除率不仅是“有效血容量”增加的结果，而且V1受体刺激也通过一种尚待确定的机制对此有贡献。
